Overcoming the compensatory increase in NRF2 induced by NPL4 inhibition enhances disulfiram/copper-induced oxidative stress and ferroptosis in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it appears to be highly susceptible to ferroptosis. Disulfiram, an alcoholism drug, has been shown to have anticancer properties in various studies, including those on RCC. However, the mechanism of the anticancer effect of disulfiram/copper on RCC remains unclear. In this study, we investigated the impact of disulfiram/copper on RCC treatment using both RCC cells and mouse subcutaneous tumor models. Our findings demonstrate that disulfiram/copper treatment reduced the viability of RCC cells, inhibited their invasion and migration, and disrupted mitochondrial homeostasis, ultimately leading to oxidative stress and ferroptosis. Mechanistically, disulfiram/copper treatment prolonged the half-life of NRF2 and reduced its degradation, but had no effect on transcription, indicating that the disulfiram/copper-induced increase in NRF2 was not related to transcription. Furthermore, we observed that disulfiram/copper treatment reduced the expression of NPL4, a ubiquitin protein-proteasome system involved in NRF2 degradation, while overexpression of NPL4 reversed NRF2 levels and enhanced disulfiram/copper-induced oxidative stress and ferroptosis. These results suggest that overcoming the compensatory increase in NRF2 induced by NPL4 inhibition enhances disulfiram/copper-induced oxidative stress and ferroptosis in RCC. In addition, our in vivo experiments revealed that disulfiram/copper synergized with sorafenib to inhibit the growth of RCC cells and induce ferroptosis. In conclusion, our study sheds light on a possible mechanism for disulfiram/copper treatment in RCC and provides a potential synergistic strategy to overcome sorafenib resistance.

[Retracted] Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cell invasion assay data shown for the 'LSD1siRNA+DDP' experiment in Fig. 3A on p. 2515 were strikingly similar to data appearing in different form in Fig. 3 in another article written by different authors at different research institutes [Liu Y, Li M, Zhang G and Pang Z: MicroRNA-10b overexpression promotes non-small cell lung cancer cell proliferation and invasion. Eur J Med Res 18: 41, 2013]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 2511-2517, 2016; DOI: 10.3892/mmr.2016.5571].

GOLM1 Promotes Epithelial-Mesenchymal Transition by Activating TGFß1/Smad2 Signaling in Prostate Cancer.

Background: Prostate cancer (PC) is one of the most commonly diagnosed cancer in men worldwide. Epithelial-mesenchymal transition (EMT) is considered to play a crucial role in the development of the metastatic castration-resistant prostate cancer, which causes the majority of the death cases in PC. Golgi membrane protein 1 (GOLM1) is highly expressed in PC and has been identified as a driver factor for EMT in various cancers. However, its biological functions and underlying mechanisms remain ambiguous in PC. Method: GOLM1 expression level of PC was detected by Western blot and immunohistochemistry analyses. To investigate GOLM1 functions in cancer cells, we overexpressed and knocked down GOLM1 in different prostate cancer cell lines. Transwell assay and wound healing assay were used to determine the role of GOLM1 in cell EMT, such as migration and invasion abilities. TGF-ß1/Smad2 signaling pathway downstream of GOLM1 was detected by Western blot and Transwell assay. Result: GOLM1 expression is up-regulated in PC and correlated with a worse prognosis. GOLM1 promotes the abilities of migration and invasion in PC cell lines (DU145 and LNCaP). Furthermore, TGF-ß1/Smad2 signaling is positively regulated by GOLM1 to facilitate EMT in PC, whereas this role can be restored by TGF-ß1 after GOLM1 knockdown or be abrogated by p-Smad inhibitor SB431542. Conclusion: GOLM1 is significantly upregulated in PC and acts as a critical oncogene by promoting PC cell EMT process by activating TGF-ß1/Smad2 signaling pathway. Therefore, GOLM1 has the potential to be a biomarker for PC diagnosis and to predict the prognosis of PC patients. It is of great significance to seek effective and specific inhibitor of GOLM1 for PC treatment as well.

A Reliability System Evaluation Model of NoC Communication with Crosstalk Analysis from Backend to Frontend.

Network on chip (NoC) is the main solution to the communication bandwidth of a multi-processor system on chip (MPSoC). NoC also brings more route requirements and is highly prone to errors caused by crosstalk. Crosstalk has become a major design problem in deep-submicron NoC communication design. Hence, a crosstalk error model and corresponding reliable system with error correction code (ECC) are required to make NoC communication reliable. In this paper, a reliability system evaluation model (RSE) of NoC communication with analysis from backend to frontend has been proposed. In the backend, a crosstalk error rate model (CER) is established with a three-wire RLC coupling model and timing constraints. The CER is used to establish functional relations between interconnect spacing, length and signal frequency, and test system reliability. In the frontend, a reliability system performance model (RSP) is established with a CER, reliability method cost and bandwidth. The RSE summarizes the frontend and backend model. In order to verify the RSE model, we propose a reliability system with a hybrid automatic repeat request technique (RSHARQ). Simulation demonstrates that the CER model is close to real circuit design. Through the CER and RSP model, the performance of RSHARQ could be simulated.

DOT1L promotes cell proliferation and invasion by epigenetically regulating STAT5B in renal cell carcinoma.

DOT1L, the only histone H3 lysine 79 methyltransferase, has a prominent effect on promoting the progression of various malignancies, yet the functional contribution of DOT1L to renal cell carcinoma (RCC) progression remains unclear. DOT1L is overexpressed in RCC and linked to poor clinical outcomes. Chemical (SGC0946) or genetic suppression of DOT1L attenuates the growth and invasion of renal cancer cells and results in S-phase arrest. STAT5B expression was suppressed after DOT1L knockdown, and STAT5B overexpression rescued the DOT1L silencing-induced decrease in cell proliferation. DOT1L was found to epigenetically promote the transcription of STAT5B via H3K79me2, and CDK6 acted as a downstream effector of STAT5B to mediate cell cycle arrest. Our study confirmed that DOT1L promotes STAT5B expression in a histone methyltransferase-dependent manner. Downregulation of DOT1L inhibited RCC proliferation and invasion. Thus, targeting DOT1L might be a potential therapeutic intervention for RCC.

Lysine-specific demethylase 1 aggravated oxidative stress and ferroptosis induced by renal ischemia and reperfusion injury through activation of TLR4/NOX4 pathway in mice.

Acute kidney injury (AKI) is mainly caused by renal ischaemia reperfusion injury (IRI). Lots of evidence suggests that ferroptosis and oxidative stress play the vital role in renal IRI. However, the specific mechanism of renal IRI has not been fully elucidated. lysine-specific demethylase 1 (LSD1) has been shown to regulate the pathogenesis of kidney disease. In this study, we firstly found that LSD1 was positively related to renal IRI. TCP, a classical LSD1 inhibitor, could alleviate tissue damage induced by renal IRI. Inhibition of LSD1 with either TCP or LSD1 knockdown could alleviate ferroptosis and oxidative stress caused by IRI both in vivo and in vitro. Furthermore, the results showed that suppression of LSD1 decreased the expression of TLR4/NOX4 pathway in HK-2 cells subjected to H/R. With the si-RNA against TLR4 or NOX4, it showed that the silence of TLR4/NOX4 reduced oxidative stress and ferroptosis in vitro. Moreover, to demonstrate the crucial role of TLR4/NOX4, TLR4 reduction, mediated by inhibition of LSD1, was compensated through delivering the adenovirus carrying TLR4 in vitro. The results showed that the compensation of TLR4 blunted the alleviation of oxidative stress and ferroptosis, induced by LSD1 inhibition. Further study showed that LSD1 activates TLR4/NOX4 pathway by reducing the enrichment of H3K9me2 in the TLR4 promoter region. In conclusion, our results demonstrated that LSD1 inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal IRI.

Discovery of a wild, genetically pure Chinese giant salamander creates new conservation opportunities.

Effective conservation of threatened biota relies on accurate assessments and scientific guidance. As an unfortunate example, Chinese giant salamanders ( Andrias, CGS) remain critically endangered in nature. Misguided conservation efforts, e.g., commercial propagation and releasing of millions of likely non-indigenous or interspecific hybrids, have further compromised conservation initiatives. Limited information on wild populations of CGS poses a significant conservation challenge. Following 18-month long field monitoring, we now report the discovery of a wild population of CGS in a closed nature reserve in Jiangxi Province, China. Genomic assessments reveal its genetic distinctiveness and do not detect genetic admixture with other species. Based on morphological and molecular evidences, we describe this CGS as a new species Andrias jiangxiensis sp. nov. This is the only known species of CGS today with a genetically pure, reproducing, in situ population. This discovery emphasizes the important role that closed nature reserves play in protecting species, and the necessity of integrating long-term field monitoring and genetic assessments. It sets a new pathway for discovering and conserving endangered species, especially for those biotas that are similarly being extirpated by anthropogenic translocations and overexploitation.

The functions of clusterin in renal mesenchymal stromal cells: Promotion of cell growth and regulation of macrophage activation.

Clusterin (CLU) increases resistance to renal ischemia-reperfusion injury and promotes renal tissue repair. However, the mechanisms underlying of the renal protection of CLU remain unknown. Mesenchymal stromal cells (MSCs) may contribute to kidney cell turnover and injury repair. This study investigated the in vitro functions of CLU in kidney mesenchymal stromal cells (KMSCs). KMSCs were grown in plastic culture plates. Cell surface markers, apoptosis and phagocytosis were determined by flow cytometry, and CLU protein by Western blot. There were no differences in the expression of MSC markers (positive: CD133, Sca-1, CD44, CD117 and NG2, and negative: CD34, CD45, CD163, CD41, CD276, CD138, CD79a, CD146 and CD140b) and in the trilineage differentiation to chondrocytes, adipocytes and osteocytes between wild type (WT) and CLU knockout (KO) KMSCs. CLU was expressed intracellularly and secreted by WT KMSCs, and it was up-regulated by hypoxia. CLU did not prevent hypoxia-induced cell apoptosis but promoted cell growth in KMSC cultures. Furthermore, incubation with CLU-containing culture medium from WT KMSCs increased CD206 expression and phagocytic capacity of macrophages. In conclusion, our data for the first time demonstrate the function of CLU in the promotion of KMSCs proliferation, and it may be required for KMSCs-regulated macrophage M2 polarization and phagocytic activity.

Knockdown of TRIM8 Protects HK-2 Cells Against Hypoxia/Reoxygenation-Induced Injury by Inhibiting Oxidative Stress-Mediated Apoptosis and Pyroptosis via PI3K/Akt Signal Pathway.

BACKGROUND: Acute kidney injury (AKI) emerges as an acute and critical disease. Tripartite motif 8 (TRIM8), one number of the TRIM protein family, is proved to participate in ischemia/reperfusion (I/R) injury. However, whether TRIM8 is involved in renal I/R injury and the associated mechanisms are currently unclear. PURPOSE: This study aimed to investigate the precise role of TRIM8 and relevant mechanisms in renal I/R injury. MATERIALS AND METHODS: In this study, human renal proximal tubular epithelial cells (HK-2 cells) underwent 12 hours of hypoxia and 2 h, 3 h or 4 h of reoxygenation to establish an in vitro hypoxia/reoxygenation (H/R) model. The siRNAs specific to TRIM8 (si-TRIM8) were transfected into HK-2 cells to knockdown TRIM8. The cell H/R model included various groups including Control, H/R, H/R+DMSO, H/R+NAC, si-NC+H/R, si-TRIM8+H/R and si-TRIM8+LY294002+H/R. The cell viability and levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), mRNA, apoptotic proteins, pyroptosis-related proteins and PI3K/AKT pathway-associated proteins were assessed. RESULTS: In vitro, realtime-quantitative PCR and western-blot analysis showed that the mRNA and protein expression of TRIM8 were obviously upregulated after H/R treatment in HK-2 cells. Compared with the H/R model group, knockdown of TRIM8 significantly increased cell viability and reduced the levels of ROS, H2O2, apoptotic proteins (Cleaved caspasebase-3 and BAX) and pyroptosis-related proteins (NLRP3, ASC, Caspase-1, Caspase-11, IL-1ß and GSDMD-N). Western-blot analysis also authenticated that PI3K/AKT pathway was activated after TRIM8 inhibition. The application of 5 mM N-acetyl-cysteine, one highly efficient ROS inhibitor, significantly suppressed the expression of apoptotic proteins and pyroptosis-related proteins. Moreover, the combined treatment of TRIM8 knockdown and LY294002 reversed the effects of inhibiting oxidative stress. CONCLUSION: Knockdown of TRIM8 can alleviate H/R-induced oxidative stress by triggering the PI3K/AKT pathway, thus attenuating pyropyosis and apoptosis in vitro.

RCAN1.4 attenuates renal fibrosis through inhibiting calcineurin-mediated nuclear translocation of NFAT2.

Chronic kidney disease (CKD) is thus deemed to a global health problem. Renal fibrosis, characterized by accumulation of extracellular matrix (ECM) components in the kidney, is considered a common pathway leading to CKD. Regulator of calcineurin1 (RCAN1), identified as a competitive endogenous inhibitor of the phosphatase calcineurin, participates in ECM deposition in various organs. However, the role of RCAN1 in renal fibrosis remains unclear. Here, unilateral ureteral obstruction (UUO), a well-known model to induce renal fibrosis in vivo, was performed on mice for a week. To overexpress RCAN1.4 in vivo, recombinant adeno-associated virus 9-packed RCAN1.4 over-expression plasm was employed in mice kidney. Lentivirus-packed RCAN1.4 over-expression plasm was employed to transfer into HK-2 and NRK-49F cells in vitro. The results indicated that RCAN1.4 expression was impaired both in UUO-induced renal fibrosis in vivo and TGF-ß1-induced renal fibrosis in vitro. However, knocking in of RCAN1.4 suppressed the production of extracellular matrix (ECM) both in vivo and in vitro. Furthermore, in vitro, the apoptosis-related proteins, including the ratio of Bax/Bcl-2 and cleaved-caspase3, were elevated in cells transfected with RCAN1.4 overexpression plasmid. In addition, we found that RCAN1.4 could rugulated NFAT2 nuclear distribution by inhibiting calcineurin pathway. So overexpression of RCAN1.4 could reverse renal fibrosis, attenuate ECM related protein accumulation, promote apoptosis of myofibroblast via inhibiting Calcineurin/NFAT2 signaling pathway. Taken together, our study demonstrated that targeting RCAN1.4 may be therapeutic efficacy in renal fibrosis.

Modified completely intrafascial radical cysprostatectomy for bladder cancer: a single-center, blinded, controlled study.

BACKGROUND: We have proposed a modified, completely intrafascial radical cysprostatectomy (RC) to treat bladder cancer patients with the aim of preserving the patients' post-surgical urinary control and erectile function. This study aimed to evaluate the oncological and functional outcomes of this innovation relatively to that with the conventional technique. METHODS: A retrospective, single-center, blinded, and controlled study was conducted using the medical data of patients since the past 5 years from the hospital database. A total of 44 patients were included, including 20 who received complete intrafascial cysprostatectomy and 24 who received conventional interfascial surgeries. The patients' continent and sexual information of 1-year follow-up after the surgery were extracted. The oncological and functional outcomes of the 2 groups were compared and analyzed. RESULTS: The demographics parameters of the 2 groups showed no significant difference. The results of follow-up of the oncological outcomes did not reveal any significant difference between the completely intrafascial group and the conventional interfascial group in terms of the positive surgical margins, local recurrences, and distant metastasis. Patients following neobladder diversion in the intrafascial group showed a faster recovery of the urinary control, with a 76.9% (10/13) daytime continent rate at 3-month, as well as 46.2% (6/13) and 58.3% (7/12) nighttime continent rates at 3-month and 6-month, respectively. Regarding the sexual functions, our results revealed significant advantages in favor of completely intrafascial technique on the post-surgical International Index of Erectile Function (IIEF)-5 score at 3-, 9-, and 12-month follow-up relative to that with the conventional interfascial process. Thus, the IIEF score of patients in the intrafascial group was 11.4 ± 3.5 at 3-month, 14.1 ± 3.6 at 9-month, and 15.2 ± 3.8 at 12-month follow-up after the cystectomy, which was significantly greater than that of the patients in the control group. CONCLUSIONS: Our novel data illustrated that the modified completely intrafascial technique could result in a better sexual function and faster continence recovery for patients following RC, without any compromise in the cancer control. Thus, this technique could be considered as an alternative extirpative technique for bladder cancer treatment in a clinical setting.

The H3K9 histone methyltransferase G9a modulates renal ischemia reperfusion injury by targeting Sirt1.

Ischemia reperfusion (IR) injury dampens renal function and usually confers a great risk of renal failure. Aberrant expression of G9a, a H3K9 methyltransferase of mammalian histone, has been implicated as a driving event in various kidney diseases. However, the role of G9a plays in renal IR injury is required to be clarified. Herein, our results showed that renal IR injury resulted in a rapid elevation of G9a, accompanying the down-regulation of Sirt1, a deacetylase that has been reported to afford renoprotection. Genetic overexpression or therapeutic activation of Sirt1 efficiently ameliorated renal IR injury by elevating anti-oxidative genes expression and reducing the accumulation of reactive oxygen species, including O2·- and ·OH. In addition, inhibition of G9a activity by BIX01294 (BIX) alleviated IR injury through abolishing O2·- and ·OH levels in a Sirt1-dependent manner. Mechanistically, we observed that demethylated H3K9 was accumulated on the Sirt1 promoter in renal IR injury. Silencing or suppression of G9a activity erased H3K9me2 from Sirt1 promoter and normalized Sirt1 expression. Further exploration revealed that G9a interacted with chromobox homolog 1 (CBX1) to catalyze H3K9 de-methylation and formed a transcription repressor complex on the Sirt1 promoter, ultimately repressing Sirt1 transcription. In this study, we provided strong evidence that G9a modulated renal IR injury through cooperation with CBX1 to form a transcription repressor complex on the Sirt1 promoter and regulate O2·- and ·OH generation, indicating that G9a-Sirt1 axis might be a promising therapeutic target in an epigenetic manner.

Long-term urbanization impacts the eastern golden frog (Pelophylax plancyi) in Shanghai City: Demographic history, genetic structure, and implications for amphibian conservation in intensively urbanizing environments.

Understanding the mechanisms of how urbanization influences the evolution of native species is vital for urban wildlife ecology and conservation in the Anthropocene. With thousands of years of agriculture-dominated historical urbanization followed by 40 years of intensive and rapid urbanization, Shanghai provides an ideal environment to study how the two-stage urbanization process influences the evolution of indigenous wildlife, especially of anuran species. Therefore, in this study, we used mitochondrial Cyt-b gene, microsatellite (SSR), and single nucleotide polymorphism (SNP) data to evaluate the demographic history and genetic structure of the eastern golden frog (Pelophylax plancyi), by sampling 407 individuals from 15 local populations across Shanghai, China. All local populations experienced bottlenecks during historical urbanization, while the local populations in urban areas maintained comparable contemporary effective population sizes (N e) and genetic diversity with suburban and rural populations. Nevertheless, the rapid modern urbanization has already imposed significant negative effects to the integrity of populations. The 15 local populations were differentiated into eight genetic clusters, showing a spatial distribution pattern consistent with the current urbanization gradient and island-mainland geography. Although moderate gene flow still occurred from the rural peripheral cluster to urban and suburban clusters, population fragmentation was more serious in the urban and suburban populations, where higher urbanization levels within 2-km radius areas showed significant negative relationships to the N e and genetic diversity of local populations. Therefore, to protect urban wildlife with limited dispersal ability, improving conditions in fragmented habitat remnants might be most essential for local populations living in more urbanized areas. Meanwhile, we highlight the need to preserve large unfragmented rural habitats and to construct corridor networks to connect discrete urban habitat remnants for the long-term wildlife conservation in intensively urbanizing environments.

Downregulation of lysine-specific demethylase 1 enhances the sensitivity of hormone-sensitive prostate cancer cells to androgen deprivation therapy.

Lysine-specific demethylase 1 (LSD1) plays an important role in androgen receptor (AR) signaling, and LSD1 levels are associated with prostate cancer (PCa) progression. The present study investigated the association between the downregulation of LSD1 and the proliferation and invasiveness of PCa cells, as well as the effect of LSD1 on the androgen deprivation therapy (ADT)-induced apoptosis of PCa cells. The effect of the inhibition of LSD1 combined with ADT on PCa cell apoptosis was characterized. Furthermore, the mechanisms underlying LSD1-mediated apoptosis induced by ADT in PCa cells were investigated. Downregulation of LSD1 impaired the proliferation and invasiveness of PCa cells. Moreover, downregulation of LSD1 enhanced the apoptosis of PCa cells induced by bicalutamide in vitro. Downregulation of LSD1 decreased PSA expression, increased caspase 3 and Bax expression, decreased Bcl-2 expression and consequently enhanced castration-induced PCa cell apoptosis in vivo. These findings indicated that downregulation of LSD1 could effectively enhance the efficacy of ADT for hormone- sensitive PCa, demonstrating that this could be a promising adjunctive therapy with ADT for this disease.

Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys.

Clusterin (CLU) is a multifunctional protein localized extracellularly and intracellularly. Although CLU-knockout (KO) mice are more susceptible to renal ischemia-reperfusion injury (IRI), the mechanisms underlying the actions of CLU in IRI are not fully understood. Macrophages are key regulators of IRI severity and tissue repair. Therefore, we investigated the role of CLU in macrophage polarization and phagocytosis. Renal IRI was induced in wild-type (WT) or CLU-KO C57BL/6 mice by clamping the renal pedicles for 30 min at 32°C. Peritoneal macrophages were activated via an intraperitoneal injection of lipopolysaccharide (LPS). Renal tissue damage was examined using histology, whereas leukocyte phenotypes were assessed using flow cytometry and immunohistochemistry. We found that monocytes/macrophages expressed the CLU protein that was upregulated by hypoxia. The percentages of macrophages (F4/80+ , CD11b+ or MAC3+ ) infiltrating the kidneys of WT mice were significantly less than those in CLU-KO mice after IRI. The M1/M2 phenotype ratio of the macrophages in WT kidneys decreased at day 7 post-IRI when the injury was repaired, whereas that in KO kidneys increased consistently as tissue injury persisted. In response to LPS stimulation, WT mice produced fewer M1 macrophages, but not M2, than the control did. Phagocytosis was stimulated by CLU expression in macrophages compared with the CLU null controls and by the exogenous CLU protein. In conclusion, CLU suppresses macrophage infiltration and proinflammatory M1 polarization during the recovery period following IRI, and enhances phagocytic activity, which may be partly responsible for tissue repair in the kidneys of WT mice after injury.

A deep learning network-assisted bladder tumour recognition under cystoscopy based on Caffe deep learning framework and EasyDL platform.

BACKGROUND: Cystoscopy plays an important role in the diagnosis of bladder tumours. As a typical representative of the deep learning algorithm, the convolutional neural network has shown great advantages in the field of image recognition and segmentation. METHODS: One thousand two photographs of normal bladder tissue and 734 photos of bladder tumours under cystoscopy were taken from 175 patients. Caffe deep learning framework and EasyDL platform were used to structure and train the model. The trained model from the EasyDL platform was deployed on a mobile phone. RESULTS: The accuracy rate of the neural network to recognise the bladder cancer based on Caffe framework was 82.9%, and the data on the EasyDL platform were 96.9%. The model from EasyDL platform could discern bladder cancer accurately on the phone and website. CONCLUSION: The deep learning network could recognise the bladder cancer accurately. Deploying that model on the mobile phone was useful for clinical use.

Automatic recognition of bladder tumours using deep learning technology and its clinical application.

BACKGROUND: Bladder cancer is a kind of tumors with a high recurrence rate. The improvement of the cure rate and prognosis of bladder tumor depends on the accurate recognition of bladder tumor under the cystoscope. AIMS: To verify that deep learning technology can identify bladder cancer images. MATERIALS AND METHODS: In this study, 1200 cystoscopic cancer images from 224 patients with bladder cancer and 1150 cystoscopic images from 221 patients with no bladder cancer were collected. Three convolutional neural networks (LeNet, AlexNet and GoogLeNet), and the EasyDL deep learning platform were used to train deep learning models to distinguish images of bladder cancer. The diagnostic efficiency of deep learning model and urology experts was compared. RESULTS: The efficiency of EasyDL was the highest, and the accuracy was 96.9%. The efficiency of GoogLeNet was the second highest, and the accuracy was 92.54%. Among the 33 bladder cancer nodes and 11 no bladder cancer nodes, the accuracy of the neural network was 83.36% and that of medical experts was 84.09% (p > 0.05). DISCUSSION: This study used convolutional neural networks to recognize bladder tumor in the clinical. Although these three networks (LeNet, AlexNet and GoogLeNet) had a relatively basic network architecture, they achieved good results in the classification task of cystoscopic images. The deep learning system had a recognition efficiency no less than that of experienced clinical experts. CONCLUSION: This study proved the validity of the convolutional neural network for bladder tumor diagnosis based on the cystoscope.

Resveratrol inhibits TNF-α-induced inflammation to protect against renal ischemia/reperfusion injury in diabetic rats.

PURPOSE: To examine effects of resveratrol on renal ischemia/ reperfusion injury (I/R) in a streptozotocin (STZ)-induced diabetic rat model. METHODS: Twenty-four male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: Sham group, I/R group and Resveratrol group (n=8). Resveratrol (RSV) was administered at a dose of 10 mg.kg-1.d-1 fourteen days prior to suffering from I/R. Renal function, histology, SOD, MDA, TUNEL assay and expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, Bcl2 and Bax were analyzed. RESULTS: Administration of RSV significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen and MDA; in the other hand, it significantly increased the serum levels of SOD. The protective effect of RSV was also reflected on histologic evaluation. RSV reduced the number of apoptotic cells as determined by TUNEL assay. RSV significantly reduced the protein expression of TNF-α, IL-1ß, NF-κB-P65, COX-2 and Caspase3, and Bax. Meanwhile, RSV significantly increased the protein expression of Bcl2. CONCLUSION: RSV attenuated I/R-induced renal injury in diabetic rats through the modulation of oxidative stress and TNF-α-stimulated inflammation.

The effects of dog management on Echinococcus spp. prevalence in villages on the eastern Tibetan Plateau, China.

BACKGROUND: The pastoral area of the eastern Tibetan Plateau is highly endemic for human echinococcosis. Domestic dogs are the main definitive host for the transmission of both Echinococcus granulosus (sensu lato) and E. multilocularis to humans. To control the infection risks, a national-level canine echinococcosis prevention and control programme has been implemented since 2015 in Shiqu County, Ganze Tibetan Autonomous Prefecture, Sichuan, China. The objective of this study was to evaluate its effect on Echinococcus spp. prevalence in dogs. METHODS: We surveyed 69 households with 84 owned dogs, for dog fecal samples and dog keeping information in the villages of Rizha and Eduoma. A total of 105 dog fecal samples (75 from owned dogs and 30 unknown dog fecal samples) were collected between 2015-2017 to determine Echinococcus spp. prevalence using copro-PCR. Eight variables based on household surveys were included into a logistic regression model for significant risk factors to canine echinococcosis prevalence in dogs. RESULTS: Between 2015-2017, the overall Echinococcus spp. copro-DNA prevalence decreased significantly in dogs from 51.2% (2015) to 20.0% (2017) in Rizha, and insignificantly from 11.5% (2016) to 4.3% (2017) in Eduoma. Echinococcus multilocularis was the most prevalent species continually copro-DNA detected during the entire study period, while E. granulosus was rare and not detected in 2017. Echinococcus shiquicus copro-DNA prevalence (a probable non-zoonotic wildlife species) was as high in dogs as that of E. multilocularis, although only detected in 2015 in Rizha. Unleashed dog feces were mainly collected in Rizha in 2015. Although 93.2% of owned dogs were leashed, and the monthly praziquantel dosing rate reached 97%, E. multilocularis infection could still be detected in 11.1% of owned dogs in 2017. Monthly deworming, leashing dogs 24 h per day, and the avoidance of dogs feeding on livestock viscera were significant measures to prevent canine echinococcosis infection in owned dogs. CONCLUSIONS: Carrying out a canine echinococcosis prevention and control programme can significantly decrease Echinococcus spp. prevalence. The potential contact between leashed dogs and wild small mammals is still a risk for re-infection of owned dogs with E. multilocularis. This study shows that the long-term application of regular dog treatment with praziquantel in the vast and remote echinococcosis endemic areas of the eastern Tibetan Plateau can reduce transmission in dogs but remains a challenging intervention.