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Cryptorchidism-caused adult infertility is a common component of idiopathic reasons for male infertility. Retinoic acid (RA) has a vital effect on the spermatogenesis process. Here, we found that the expression of c-Kit, Stra8, and Sycp3 could be up-regulated via the activation of retinoic acid receptor α (RARα) after RA supplementation in neonatal cryptorchid infertile rats. We also demonstrated that the protein expression of PI3K, p-Akt/pan-Akt, and p-mTOR/mTOR was higher in cryptorchid than in normal testes, and could be suppressed with RA in vivo. After RA treatment in infertile cryptorchid testis in vivo, the levels of the autophagy proteins LC3 and Beclin1 increased and those of P62 decreased. Biotin tracer indicated that the permeability of blood-testis barrier (BTB) in cryptorchid rats decreased after RA administration. Additionally, after blocking the RARα with AR7 (an RARα antagonist) in testicle culture in vitro, we observed that compared with normal testes, the PI3K-Akt-mTOR signaling pathway and the autophagy pathway was increased and decreased, respectively, which were coincident with cryptorchisd testes in vivo. Additionally, the appropriate concentrations of RA treatment could depress the PI3K-Akt-mTOR signaling pathway and improve the autophagy pathway. The results confirmed that RA can rehabilitate BTB function and drive key protein levels in spermatogonial differentiation through depressing the PI3K-Akt-mTOR signaling pathway via RARα.

To weaken the noise pollution of wet cooling towers, a large-scale wet cooling tower with a 660 MW unit is used as an example, and the water-splashing noise is measured in a field test. The sound source characteristics are determined based on the field test results, and the sound source surface is specified as the initial parameters of the simulation. Then, the noise propagation model for the wet cooling tower is established based on the ray-tracing method, with a maximum relative error of only 2.22 %. Two noise reduction schemes, vertical and curved sound barriers, are proposed based on this model. Furthermore, the noise reduction effects of two different types of sound barriers are investigated. Under identical conditions, the simulation reveals that the vertical sound barrier performs better than the curved sound barrier in terms of noise reduction. In addition, The results also show that a vertical sound barrier with a length of 90 meters, a height of 10 meters, and a distance of 15 meters from the tower is an optimal scenario, with an A-weighted sound pressure level (A-SPL) of just 42.08 dB(A). In summary, the noise problem associated with wet cooling towers may be effectively addressed in this instance.

Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation.

Renal fibrosis occurs largely through epithelial–mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-β (TGF-β)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-β/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-β/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.

Fillings are the core part of wet cooling towers, and generally speaking, the fillings are arranged in an equidistant pattern, which actually hampers the heat and mass transfer process. So the non-equidistant fillings which is the combination of large-spacing and small-spacing fillings are adopted to enhance the thermal performance. In this study, numerical simulation was conducted on one real wet cooling towers equipped for a 600 MW unit to study the relatively optimal combination of 26 mm and 30 mm spacing fillings (30 mm fillings are arranged in the inner zone and 26 mm fillings are stalled in the outer zone). The simulation results indicated that, compared with conventional equidistant fillings, the thermal and resistance performance improve partly under the non-equidistant fillings pattern. After adopting non-equidistant fillings, the aerodynamic field and the temperature field improve significantly. Furthermore, with the increase of the inner zone radius R1, the water temperature drop Δ t , cooling efficiency η and Merkel number N rise first and then decline, and the relatively optimal inner radius is 47.5 m in this case. When R1 = 47.5 m, compared with 26 mm equidistant fillings condition, Δ t , η, and N increase about 0.13 °C, 0.8%, and 0.03. And the ventilation rate G increases by about 751.32 kg/s at most. While the ambient air temperature changes, the non-equidistant fillings can also improve the cooling performance. Under the summer typical conditions, compared with all 26 mm and 30 mm equidistant fillings, the Δ t with the relatively optimal non-equidistant fillings rises by 0.17 °C and 0.2 °C, respectively.

Stem cells present in urine possess regenerative capacity to repair kidney injury. However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown. The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals. Methods: Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years). Results: There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors. However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls. In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (p

The study was designed to quantify the thermal conditions in tall atria in office buildings to serve as a starting point towards understanding their performance. The simulation study of a non-segmented and segmented atrium of 250 m height reveals indoor air temperature, wind velocity contours and wind pressure coefficients at various heights of each atrium type. In a hot and humid climate like that of Singapore, the internal temperatures within each atrium stack remain constant at 27°C. However, the wind velocity in the non-segmented atrium (of 0.5 - 0.7 m/s) is lower than acceptable (0.9 m/s) for human occupancy. Adding segments and a larger inlet to the atrium solves the problem of low wind velocity without increasing the effective ambient temperature within the atrium stack. Additionally, the segmented atrium offers the advantage of displaying lower buoyancy forces by lowering the pressure differential within a tall stack thereby providing better comfort conditions.

To improve the heat and mass transfer performance of large wet cooling towers, a synergetic optimization method of non-equidistant fillings and non-uniform water distribution was proposed in this paper. The impact of the optimization scheme on the cooling performance was studied for the cooling tower equipped for a 600 MW unit. Firstly, the fillings were divided into two zones, and the optimized inner fillings radius was obtained according to the different non-equidistant fillings patterns, namely the optimized radius dividing point in the filings zone. Then, the cooling performance variation under different non-uniform water distribution patterns was discussed based on this optimized radius dividing point. The simulation results showed that the synergetic optimization coupling the fillings and water-spraying zones improves significantly the uniformity of the air dynamic and temperature field. The water temperature drops and ventilation rate all increase firstly and then decrease with the increase of the water distribution ratio in the inner zone. Compared with the equidistant fillings layouts of 26 mm and 30 mm, after the synergetic optimization, the outlet water temperature drops increase by 0.21 ℃, 0.22 ℃, and the ventilation rate enhances by 6.68%, 1.13% respectively in the design condition, but 0.28 ℃, 0.31℃ and 7.03%, 1.53% in the typical operating condition in summer. Additionally, the evaporation loss all decreases by about 3.3% in the design condition by comparison with the equidistant fillings layouts of 26 mm and 30 mm, but increases in the typical operating condition in summer.

Numerical simulation is an important means to study the thermal and resistance characteristics of natural draft wet cooling towers. The treatment method of droplet diameter distribution in the rain zone directly affects the accuracy of the numerical model, which becomes a key problem in the numerical simulation at present. In this paper, to provide an appropriate treatment method of droplet diameter, three kinds of droplet diameter distribution treatment models for the numerical simulation are studied and compared, including equivalent diameter method (EDM), Gaussian distribution method (GDM), and diameter distribution method based on field test (FTDM), and the influences of each treatment method on the simulation results are presented respectively, which provide references for the subsequent numerical simulation. It is found that each method can reasonably simulate the thermal characteristics of the cooling tower by determining their key parameters, but the temperature drop calculated by FTDM is the most accurate with a relative error of 0.58%. Additionally, FTDM can most accurately simulate the pressure drop with a relative error of 4.18% and the motion trajectory of the water droplets, so the FTDM should be given priority under the premise of known the droplet diameter distribution data of the tower.

OBJECTIVE: To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP). METHODS: Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue. RESULTS: A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group (P < 0.01). CONCLUSION: Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.

Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism.Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-β (TGF-β)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls.The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-β/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation.The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-β/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.

Background It has been recognized that the incidence of prostatic utricle in boys is increasing and is closely associated with diseases such as hypospadias. However, the clinical features of prostatic utricle with normal external genitalia have received little attention. Methods Based on this, a series of 22 male children with prostatic utricles has been compiled by adding our 3 patients to 19 cases reported. All children enrolled had normal external genitalia. Clinical data of the case was reviewed. Results Urinary tract infection, purulent urethral discharge and pyuria were the most common presenting chief complaint (41%), irritative lower urinary tract symptoms were present in 17% of cases, obstructive lower urinary tract symptoms were noted in 14%. Urinary retention has been reported in 18% and epididymitis has been reported in 14%. Relatively rare clinical symptoms are abdominal pain, hematuria, and hematospermia. A case of calculus formation and a case of neoplasia within the prostatic utricle has been reported. A cystic mass found by digital rectal examination is the most common presenting sign. A utricular lesion posterior to the bladder was revealed by imaging examination. Unilateral renal agenesis was associated in 32% of reports. Non-surgical approach was chosen in 3 cases, transrectal ultrasonography guided aspiration has been reported in 1 case. Endoscopic techniques were used in 3 cases. Open excision was used in 11 cases. The laparoscopic excision was chosen in 3 cases and Robot-assisted laparoscopy was reported in 1 case. Symptoms and signs disappeared after treatment in all children, and no recurrence occurred during follow-up. Conclusions Prostate utricles without external genital anomalies are rarely reported in children, and are easily missed and misdiagnosed, often accompanied by recurrent urinary tract infections, lower urinary tract symptoms, epididymitis, dysuria and other symptoms. Imaging studies can confirm the diagnosis. Symptomatic and large utricles should be actively treated. The treatment program should be based on the age, clinical symptoms, and size and location of the utricle.

Air pollutants existing in the environment may have negative impacts on human health depending on their toxicity and concentrations. Remote sensing data enable researchers to map concentrations of various air pollutants over vast areas. By combining ground-level concentrations with population data, the spatial distribution of health impacts attributed to air pollutants can be acquired. This study took five highly populated and severely polluted provinces along the Huaihe River, China, as the research area. The ground-level concentrations of four major air pollutants including nitrogen dioxide (NO2), sulfate dioxide (SO2), particulate matters with diameter equal or less than 10 (PM10) or 2.5 micron (PM2.5) were estimated based on relevant remote sensing data using the geographically weighted regression (GWR) model. The health impacts of these pollutants were then assessed with the aid of co-located gridded population data. The results show that the annual average concentrations of ground-level NO2, SO2, PM10, and PM2.5 in 2016 were 31 &micro, g/m3, 26 &micro, g/m3, 100 &micro, g/m3, and 59 &micro, g/m3, respectively. In terms of the health impacts attributable to NO2, SO2, PM10, and PM2.5, there were 546, 1788, 10,595, and 8364 respiratory deaths, and 1221, 9666, 46,954, and 39,524 cardiovascular deaths, respectively. Northern Henan, west-central Shandong, southern Jiangsu, and Wuhan City in Hubei are prone to large health risks. Meanwhile, air pollutants have an overall greater impact on cardiovascular disease than respiratory disease, which is primarily attributable to the inhalable particle matters. Our findings provide a good reference to local decision makers for the implementation of further emission control strategies and possible health impacts assessment.

Background Autologous urothelial cells are often obtained via bladder biopsy to generate the bio-engineered urethra or bladder, while urine-derived stem cells (USC) can be obtained by a non-invasive approach. The objective of this study is to develop an optimal strategy for urothelium with permeability barrier properties using human USC which could be used for tissue repair in the urinary tract system. Methods USC were harvested from six healthy adult individuals. To optimize urothelial differentiation, five different differentiation methods were studied. The induced cells were assessed for gene and protein expression markers of urothelial cells via RT-PCR, Western blotting, and immunofluorescent staining. Barrier function and ultrastructure of the tight junction were assessed with permeability assays and transmission electron microscopy (TEM). Induced cells were both cultured on trans-well membranes and small intestinal submucosa, then investigated under histology analysis. Results Differentiated USC expressed significantly higher levels of urothelial-specific transcripts and proteins (Uroplakin III and Ia), epithelial cell markers (CK20 and AE1/AE3), and tight junction markers (ZO-1, ZO-2, E-cadherin, and Cingulin) in a time-dependent manner, compared to non-induced USC. In vitro assays using fluorescent dye demonstrated a significant reduction in permeability of differentiated USC. In addition, transmission electron microscopy confirmed appropriate ultrastructure of urothelium differentiated from USC, including tight junction formation between neighboring cells, which was similar to positive controls. Furthermore, multilayered urothelial tissues formed 2 weeks after USC were differentiated on intestine submucosal matrix. Conclusion The present study illustrates an optimal strategy for the generation of differentiated urothelium from stem cells isolated from the urine. The induced urothelium is phenotypically and functionally like native urothelium and has proposed uses in in vivo urological tissue repair or in vitro urethra or bladder modeling. Electronic supplementary material The online version of this article (10.1186/s13287-018-1035-6) contains supplementary material, which is available to authorized users.

Background Renal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis. Methods Renal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-α, IL-6, and IL-1β in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-β1-induced epithelial–mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting. Results hucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro. Conclusions Our results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-κB signaling pathway activation.

Table S4. Percentage of USC expressing tight junction markers 2Â weeks after urothelial induction assessed by immunofluorescence. (DOCX 16Â kb)

Showing characterization of human umbilical cord mesenchymal stem cells (hucMSCs). A Flow cytometry analyses of phenotypic markers of hucMSCs; positive for CD73, CD90, and CD105, and negative for CD34, CD45, and HLA-DR. B Cell linage induced differentiation. Adipogenic differentiation analyzed by Oil Red O staining; after induction, hucMSCs formed numerous Oil-Red-O-positive lipid droplets. Osteogenic differentiation analyzed by Alizarin Red staining; after induction, hucMSCs formed Alizarin Red-positive mineral nodes. Table S1 presenting cytokines and growth factor levels present in conditioned medium derived from hucMSC. Levels of insulin-like growth factor (IGF)-1, hepatocyte growth factor (HGF), stromal cell-derived factor (SDF)-1, brain-derived neurotrophic factor (BDNF), vascular cell adhesion protein (VCAM)-1, and transforming growth factor (TGF)-β in hucMSC-CM also measured using ELISA kits: human IGF-1 ELISA, human BDNF ELISA, human TGF-β ELISA (RayBiotech); and human CXCL12/SDF-1α quantikine ELISA kit, human HGF quantikine ELISA kit, human VCAM-1 quantikine ELISA kit (R&D Systems). Data expressed as mean ± SD. (DOCX 111 kb)

Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle dysfunction.

MicroRNAs (miRNAs) are small, non-coding RNAs which can serve as oncogenes or tumor suppressor genes in human cancers. Herein, the transcriptomic differences of miRNAs in ccRCC were globally assessed using publicly available microarray dataset (GSE71302) from Gene Expression Omnibus (GEO) and we identified miR-138 as a potential onco-suppressive miRNA. We further found that the expression of miR-138 was dramatically decreased in ccRCC cell lines and clinical ccRCC tissue samples, and the low miR-138 expression was closely correlated with tumor progression and prognosis in ccRCC patients. Overexpression of miR-138 inhibited, whereas downregulation of miR-138 promoted, the proliferation, migration and invasion of ccRCC cells in vitro, suggesting that miR-138 may function as a tumor suppressor in ccRCC. Furthermore, for the first time, we identified the EMT-related transcription factor SOX4 as a direct target gene of miR-138, evidenced by the direct binding of miR-138 with the 3’UTR of SOX4. Notably, the EMT marker E-cadherin or vimentin was also upregulated or downregulated upon miR-138 overexpression, and these effects were restored by SOX4 overexpression. We have also shown SOX4 overexpression reversed the attenuated migratory and invasive capacities mediated by miR-138. These results revealed that miR-138 functions as a tumor suppressor in ccRCC by targeting SOX4 and the EMT process and might represent a potential target in the treatment of human ccRCC.

Uncontrolled cell proliferation and inhibition of apoptosis are considered to be vital for cancer initiation, maintenance, infiltration, metastasis and recurrence after anti-cancer therapy. Here we report the generation of a novel cell line by reprogramming child foreskin fibroblast with the full length apoptosis inhibitor gene PIWIL2. The fibroblasts transfected with PIWIL2 expressed the stem cell markers OCT-4, NANOG, SOX-2, KLF-4 and C-MYC; endoderm marker AFP and GATA6; mesoderm markers ACTA2 and BRACHYURY; and ectoderm markers NESTIN and TUBB3. The karyotype was found to be hyperdiploid. The PIWIL2 transfected fibroblast cells grew into tumorous masses within 5 weeks of subcutaneous injection into adult nude mice. Although the injected cell expressed markers for all three germlines, ectoderm, mesoderm, and endoderm, they did not form teratomas in vivo. This study indicates that the PIWIL2 gene could play a key role in cancer induction and maintenance. This method for generating induced tumorigenic cells (ITGC) provides a new research tool to study oncogenesis that in turn may lead to a better understanding of cancer etiology and the development of novel anti-cancer therapies.

// Guangping Zeng 1, * , Deying Zhang 1, * , Xing Liu 1 , Qing Kang 1 , Yiyao Fu 1 , Bo Tang 1 , Wenhao Guo 1 , Yuanyuan Zhang 2 , Guanghui Wei 1 , Dawei He 1 1 Department of Urology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China 2 Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina 27103, USA * These authors have contributed equally to this work Correspondence to: Dawei He, email: dw.he@163.com Keywords: hepatocellular carcinoma, molecular chaperone, Piwil2, Piwil4, prognosis Received: July 25, 2016 Accepted: October 28, 2016 Published: November 22, 2016 ABSTRACT Purpose: This study aimed to explore the localization and expression of P-element-induced wimpy testis-like 2 (piwil2)/Piwil4 in hepatocellular carcinoma (HCC) tissues, and analyze the correlation between co-expression pattern and prognosis of HCC. Results: Piwil2 showed 100% positive expression in the cell nucleus, with the intensity higher than in the cytoplasm. Piwil4 showed a lower intensity of expression in the cell nucleus than in the cytoplasm. The molecular chaperone Piwil2/Piwil4 had four co-expression patterns: nuclear co-expression, nuclear and cytoplasmic co-expression, cytoplasmic co-expression, and non-coexpression. The survival rate and the overall survival sequentially increased. The prognostic phenotype of the nuclear co-expression of Piwil2/Piwil4 was worse than that of non-coexpression, and the intracellular localization and expression of Piwil2 and Piwil4 were not significantly different. Methods: HCC pathological tissue samples with follow-up information (90 cases) and 2 normal control liver tissues were collected and made into a 92-site microarray. The expression of Piwil2 and Piwil4 was detected using the immunofluorescence double staining method. The differences in the expression and location of Piwil2 and Piwil4 in tumor cells were explored, and the influence of such differences on the long-term survival rate of HCC was studied using Kaplan-Meier survival curve and log-rank test. The clinical staging was analyzed according to the HCC international TNM staging criteria. Conclusions: The nuclear co-expression of Piwil2/Piwil4 indicated that patients with HCC had a worse prognostic phenotype. The molecular chaperone Piwil2/Piwil4 seems promising as a molecular marker for prognosis judgment; a single marker (Piwil2/Piwil4) cannot be used for prognosis judgment.

// Bo Liu 1,3 , Fengxia Ding 2,3 , Yang Liu 1,3 , Geng Xiong 1,4 , Tao Lin 1 , Dawei He 1 , Yuanyuan Zhang 4 , Deying Zhang 1,3 and Guanghui Wei 1 1 Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China 2 Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, China 3 Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China 4 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA Correspondence to: Deying Zhang, email: // Guanghui Wei, email: // Keywords : meta-analysis, cancer, VEGFR-TKIs, hypertensive events Received : April 28, 2016 Accepted : August 23, 2016 Published : September 01, 2016 Abstract Background: Tyrosine kinase inhibitors (TKIs) have been developed during the last decade that target the vascular endothelial growth factor receptor (VEGFR) are currently being evaluated as treatments for malignant tumors. The increased application of VEGFR-TKIs means that the probability of hypertension is a serious concern. However, the reported incidence varies markedly between clinical trials. Here, we undertook an up-to-date, comprehensive meta-analysis on clinical works to build the incidence of hypertension along with VEGFR-TKIs. The goal was to understand better of the overall venture of cancer patients’ hypertension treated with these drugs. Methods: Databases (EMBASE, PubMed, and Cochrane library) and the abstracts of the American Society of Clinical Oncology annual meeting and European Society of Medical Oncology were searched to identify related studies. 95% confidence intervals (CIs), summary incidences, and relative risk (RR) were calculated utilizing either fixed-effects models on the basis of the heterogeneity of the included studies or random-effects. Results: Seventy-two randomized controlled trials (including 30013 patients) were involved. The total incidence of high-grade and all-grade hypertensive events along with VEGFR-TKIs was 23.0% (95% CI, 20.1–26.0%) and 4.4% (95% CI, 3.7–5.0%), respectively. The use of VEGFR-TKIs remarkably enhanced the venture of developing high-grade (RR, 4.60; 95% CI, 3.92–5.40; P < 0.001) and all-grade (RR, 3.85; 95% CI, 3.37–4.40; P < 0.001) hypertensive events. Subgroup analyses revealed that the risk of a hypertensive event varied significantly in accordance with tumor type, VEGFR-TKI, trial phase, VEGFR-TKIs-based regimen, control therapy, and chemotherapy regimen. Conclusions: Patients with cancer that receive VEGFR-TKIs are at a remarkable venture of developing hypertension. Therefore, suitable treatment and monitoring should be introduced to avoid cardiovascular complications.

In this paper, a solution of monitor system of Public Transport operation vehicles is presented for realizing intelligent management of public transport. The system adopts ARM and embedded Linux operation system as the development platform, and integrates GPS (Global Position System) technology, GPRS (General Packet Radio Service) technology and embedded technology and so on. The paper mainly completed the design of hardware circuit and transplantation of embedded Linux operating system on S3C2410 chip. The system realized location tracking, communication scheduling, stops broadcasting, video monitoring, and intelligent passenger counting of public transport vehicles. The result of experiment showed that the system could improve the operation efficiency of public transport vehicles.

Insulin-like factor 3 (INSL3) regulates testicular descent during fetal life, and Insl3 gene inactivation results in cryptorchidism. Little is known, however, about whether the plasticizer diethylhexyl phthalate (DEHP), a contaminant found widely in the environment, influences INSL3 expression. In this study, primary cultures of Leydig cells from mouse embryos were treated in vitro with DEHP. We also treated pregnant mice with DEHP from gestation day 12 to postnatal day 3 in order to study the effect of DEHP in vivo. INSL3 mRNA expression levels in primary Leydig cell cultures and in the testes of newborn mice were significantly lower following DEHP treatment. DEHP also caused detrimental morphological changes in both primary cultures of Leydig cells and the testes of newborn mice. These results suggest that the downregulation of INSL3 mRNA by DEHP might cause abnormalities of gubernacular development, which might be one of the mechanisms for development of cryptorchidism.

Copyright: © 2015 Zhang D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. *Corresponding authors: Yuanyuan Zhang, Wake Forest University, Institute for Regeneration Medicine, Winston-Salem, NC, USA, Tel: 336-713-1189; E-mail: yzhang@wakehealth.edu Guanghui Wei, Department of Urology, Children’s Hospital of Chongqing Medial University, Chongqing, China

Despite the potential of stem cells in cell-based therapy, major limitations such as cell retention, ingrowth, and trans-differentiation after implantation remain. One technique for genetic modification of cells for tissue repair is the introduction of specific genes using molecular biology techniques, such as virus integration, to provide a gene that adds new functions to enhance cellular function, and to secrete trophic factors for recruiting resident cells to participate in tissue repair. Stem cells can be labelled to track cell survival, migration, and lineage. Increasing evidence demonstrates that cell therapy and gene therapy in combination remarkably improve myogenic differentiation of implanted mesenchymal stromal cells (MSCs), revascularization, and innervation in genitourinary tissues, especially to treat urinary incontinence, erectile dysfunction, lower urinary tract reconstruction, and renal failure. This review discusses the benefits, safety, side effects, and alternatives for using genetically modified MSCs in tissue regeneration in andro-urology.