Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.

Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.

Artificial Intelligence in Pancreatic Image Analysis: A Review.

Pancreatic cancer is a highly lethal disease with a poor prognosis. Its early diagnosis and accurate treatment mainly rely on medical imaging, so accurate medical image analysis is especially vital for pancreatic cancer patients. However, medical image analysis of pancreatic cancer is facing challenges due to ambiguous symptoms, high misdiagnosis rates, and significant financial costs. Artificial intelligence (AI) offers a promising solution by relieving medical personnel's workload, improving clinical decision-making, and reducing patient costs. This study focuses on AI applications such as segmentation, classification, object detection, and prognosis prediction across five types of medical imaging: CT, MRI, EUS, PET, and pathological images, as well as integrating these imaging modalities to boost diagnostic accuracy and treatment efficiency. In addition, this study discusses current hot topics and future directions aimed at overcoming the challenges in AI-enabled automated pancreatic cancer diagnosis algorithms.

Characteristics of dissolved organic matter in point-source wastewaters at a petrochemical plant: Molecular constituents and contributions to the influent of wastewater treatment plant.

Dissolved organic matter (DOM) in point-source petrochemical wastewaters (PCWs) from different operating units is closely linked to the efficiency of wastewater treatment plant (WWTP). However, systematic studies on DOM characters of point-source PCWs and their influences on WWTP influents were seldom conducted. In this study, DOM in three low-salinity point-source PCWs and four high-salinity point-source PCWs at a typical petrochemical plant were comprehensively characterized at a molecular level. Orbitrap mass spectrometry results indicated that point-source PCWs had diverse DOM constituents tightly related to the corresponding petrochemical processes. Phenols in oily wastewaters (OW), phenols and N-containing compounds in coal partial oxidation wastewater (POXW), and naphthenic acids (NAs) and aromatic acids in crude oil electric desalting unit wastewater (EDW) were characteristic DOM constituents for low-salinity point-source PCWs. While S-containing compounds (mercaptans, thiophenes) and NAs in spent caustic liquors (SCL), alcohols and esters in butanol-octanol plant wastewater (BOW), high molecular weight aromatic ketones in phenol-acetone plant wastewater (PAW), and oxygenated NAs as well as short chain N-containing compounds in concentrate from reverse osmosis unit (ROC) were characteristic DOM constituents for high-salinity point-source PCWs. Spearman correlation analysis indicated that though with relative low pollutant contents (OW) and discharge volume (EDW), N/O/S-containing compounds of OW and EDW greatly contributed to the polar DOM constituents of low-salinity influent in WWTP (R > 0.5, P < 0.001). While N-containing compounds of ROC mainly contributed to the polar DOM of high-salinity influent (R > 0.5, P < 0.001). Though N-/S-containing species in PAW had low contents, they also posed obvious impacts on DOM constituents of high-salinity influent. Interestingly, some O-/S-containing species were newly formed during the confluent process of high-salinity point-source PCWs. The results strengthened the combined contributions of pollutants contents, discharge emission and DOM constituents of point-source PCWs to the water matrix of WWTP influents, which would provide reference for the management of PCW streams.

Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

INTRODUCTION: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. METHODS: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. RESULTS: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. CONCLUSIONS: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.

Di-n-butyl phthalate induces oversecretion of vascular endothelium-derived NAP-2 and promotes epithelial-mesenchymal transition of urothelial cells in newborn hypospadias rats.

Di-n-butyl phthalate (DBP) is a plasticizer commonly used in industrial production and is present in our daily life. It has been confirmed that DBP causes genitourinary malformations, especially hypospadias. However, the research of hypospadias mainly focusses on the genital tubercle in previous studies. In this study, we found DBP could affect the exocrine function of the vascular endothelium which disturb the development of genital nodules and induced hypospadias. We used cytokine array to find that vascular endothelium-derived NAP-2 may be a major abnormal secreted cytokine with biological functions. The transcriptomic sequencing analysis showed that abnormal activation of the RhoA/ROCK signaling pathway was the main reason for increased NAP-2 secretion. The expression levels of epithelial-mesenchymal transition (EMT) biomarkers and NAP-2 in hypospadias animal models were detected with Immunohistochemistry, Western blot, Immunofluorescence, and ELISA methods. The expression levels of NAP-2, RhoA/ROCK signaling pathway related proteins, reactive oxygen species (ROS) levels in HUVEC cells, EMT biomarkers and migration capacity of urothelial cells cocultured with HUVEC were measured with ELISA, flow cytometry, Western blot or Transwell assay for further cell experiments. The results showed that DBP leaded to NAP-2 oversecretion from vascular endothelium mainly rely on the activation of RhoA/ROCK signaling pathway and ROS accumulation. The RhoA/ROCK inhibitor fasudil could partially decrease ROS production, and both fasudil and N-acetyl-L-cysteine (NAC) could decrease NAP-2 secretion. Meanwhile, the oversecretion of NAP-2 from HUVEC in coculture system promoted EMT and migration capacity of urothelial cells, and TGF-ß inhibitor LY219761 could block the aberrant activation of EMT process. Therefore, it could be concluded that DBP increase NAP-2 secretion from vascular endothelium by RhoA/ROCK/ROS pathway, and further promote EMT in urothelial cells through TGF-ß pathway. This study provided a novel direction for studying the occurrence of hypospadias and may provide a hypospadias predictive marker in the future.

Transformation of dissolved organic matter at a full-scale petrochemical wastewater treatment plant.

Transformation of dissolved organic matter (DOM) in petrochemical wastewater (PCW) treatment has rarely been studied. In this work, low- and high-salinity PCW were collected from a treatment plant and the transformations of DOM at molecular level along the treatment processes of both PCW were comparatively investigated. By using Orbitrap MS, the polar DOM constituents were categorized into five molecular classes namely saturated compounds, aliphatics, highly unsaturated and phenolic compounds (Huph), polyphenols and condensed polycyclic aromatics (Cpla). Aliphatics (58.62%) with low molecular weight (150-250 Da) and O/C (0-0.2) were dominant in raw low-salinity PCW; while Huph (65.03%) with O/C at 0.2-0.8 were rich in raw high-salinity PCW. After full-scale treatment, differentiated DOM constituents in both raw PCWs were transformed into aliphatics and Huph with O/C at 0.3-0.5. Anoxic/Oxic treatment of low-salinity system (L-A/O) removed a high fraction of aliphatics (53.05%); while Huph with low O/C (0.1-0.3) (65.68%) in the effluent of L-A/O were further mineralized by ozonation of low-salinity system (L-ozonation). In comparison, anoxic/oxic treatment of high-salinity system (H-A/O) mainly removed unsaturated Huph (34.10%) and aliphatics (30.86%). This resulted in a decrease of dissolved organic carbon as indicated via Spearman correlation. Different from L-ozonation, ozonation of high-salinity system (H-ozonation) degraded aliphatics (26.09%) and Huph (41.85%) with a relatively high O/C (0.2-1.2). After L-A/O and L-ozonation treatments, remaining saturated compounds that were originated from raw low-salinity PCW, were removed by subsequent biological aerated filter. Comparatively, after H-A/O and H-ozonation treatments, residual Huph and aliphatics which were mainly bio-derivates and ozonated intermediates, were further removed by air flotation filter. Hence, DOM transformation of different PCWs along similar treatments varied significantly. This study provides in-depth insights on DOM transformation along a full-scale PCW treatment process.

Maternal exposure to Di-n-butyl phthalate (DBP) aggravate gestational diabetes mellitus via FoxM1 suppression by pSTAT1 signalling.

The study focused on the toxicological effect of Di-n-butyl phthalate (DBP) on the expression of Phosphorylated signal transducer and activator of transcription 1 (pSTAT1) -regulated Forkhead box protein M1 (FoxM1), which might provide a new understanding of gestational diabetes mellitus (GDM) development and a potential target for treatment. Streptozotocin (STZ) (40 mg/kg) was introduced in maternal rats by intraperitoneal injection on gestation day 0 (GD 0) in the STZ and STZ + DBP groups. DBP was introduced in maternal rats by oral feeding in the STZ + DBP group over the following 3 days (750 mg/kg/day). The changes in fasting blood glucose level in rats were detected on GD 1 and GD 5. The insulin levels in maternal rats and PIBCs were measured on GD 18. The Oral Glucose Tolerance Test (OGTT) test was performed on GD 18 to check the stability of the GDM model. The primary islet ß cells (PIBCs) were established for in vitro experiments. We examined the FoxM1 and pSTAT1 expression in pancreas by immunohistochemistry. Real-time PCR and Western blot were used to detect the pSTAR1 and FoxM1 protein and mRNA gene expression levels in PIBCs. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis was used to test the viability and apoptosis of cells. The results showed that the STZ + DBP group had higher glucose and lower insulin secretion levels than the other groups by both fasting test and OGTT. FoxM1 was significantly suppressed while pSTAT1 was highly expressed after DBP exposure. FoxM1 could be regulated by pSTAT1. DBP can influence the progression of GDM through its toxicological effect, which significantly increases the expression of pSTAT1 and suppresses FoxM1, causing a decline in ß cell viability.

Di-n-butyl phthalate (DBP) reduces epithelial-mesenchymal transition via IP3R in hypospadias during maternal exposure.

OBJECTIVE: This study focused on the oxidative stress effect of di-n-butyl phthalate (DBP) on development of the urinary system. METHODS: We examined the mRNA expression of genital tubercle (GT) in control and DBP induced hypospadias group by Affymetrix Rat 230 2.0 Array. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of inositol-1,4,5-triphate-receptor (IP3R) and epithelial-mesenchymal-transition (EMT)-related molecular markers, such as E-cadherin, ß-Catenin, Snail, N-cadherin, in the GT of hypospadiac male rats and controls. The results of array were further confirmed in vitro. The changes of intracellular calcium concentration in urethral epithelial cells were detected by Fluo-3-AM before and after DBP treatment. The levels of reactive oxygen species (ROS) in urethral epithelial cells were measured by DCFH-DA with different concentrations of DBP (0, 1, 10, 100 µmol/L) treatment. RESULTS: The mRNA expression profiles of GT in control and DBP induced hypospadias group showed high expression of IP3R and the abnormalities of EMT. Compared to the control group, the expression levels of IP3R, E-cadherin and ß-Catenin increased at both the protein and mRNA levels. However the expression levels of Snail and N-cadherin decreased. The intracellular calcium concentration increased significantly after DBP treatment. The effect of DBP on urethral epithelial cells was linked to the generation of oxidative stress. CONCLUSION: DBP can influence the development of GT through its oxidative stress effect, which significantly increases the concentration of calcium and inhibits EMT in urethral epithelial cells, and block the fusion process of urethral groove, causing the occurrence of hypospadias. This study provides a new understanding of DBP's molecular mechanisms on hypospadias and may lead to new treatment strategies for the disease.

Maternal exposure to di-n-butyl phthalate promotes Snail1-mediated epithelial-mesenchymal transition of renal tubular epithelial cells via upregulation of TGF-ß1 during renal fibrosis in rat offspring.

We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-ß expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14-18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-ß1 and EMT markers. In rat kidney tubular epithelial cells (NRK52E), ROS production increased expression levels of TGF-ß1 and subsequently contributed to the induction of Snail1-mediated EMT. Notably, DBP exposure also promoted autophagy that downregulated TGF-ß1. Taken together, our findings suggest that maternal exposure to DBP promotes EMT in tubular epithelial cells via upregulation of TGF-ß1.

Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which results in various organ pathologies. However, current treatment towards SLE is suboptimal. Erythropoietin (EPO) has been shown to promote SLE recovery, but clinical application can be limited by its haematopoiesis-stimulating effects. EPO-derived helix-B peptide (ARA290) is non-erythrogenic but has been reported to retain the anti-inflammatory and tissue-protective functions of EPO. Therefore, here we investigated the effects and potential mechanisms of ARA290 on SLE. The administration of ARA290 to pristane-induced SLE and MRL/lpr mice significantly suppressed the level of serum antinuclear autoantibodies (ANAs) and anti-dsDNA autoantibodies, reduced the deposition of IgG and C3, and ameliorated the nephritis symptoms. Moreover, the serum concentrations of inflammatory cytokine IL-6, MCP-1 and TNF-α in SLE mice were reduced by ARA290. Further, ARA290 decreased the number of apoptotic cells in kidney. In vitro experiment revealed that ARA290 inhibited the inflammatory activation of macrophages and promoted the phagocytotic function of macrophages to apoptotic cells. Finally, ARA290 did not induce haematopoiesis during treatment. In conclusion, ARA290 ameliorated SLE, which at least could be partly due to its anti-inflammatory and apoptotic cell clearance promoting effects, without stimulating haematopoiesis, suggesting that ARA290 could be a hopeful candidate for SLE treatment.

Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.

Comparison of the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy and ureteroscopic holmium laser lithotripsy in the treatment of obstructive upper ureteral calculi with concurrent urinary tract infections.

The aim of this study is to compare the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopic holmium laser lithotripsy (UHLL) as two minimally invasive procedures in managing obstructive upper ureteral calculi with concurrent urinary tract infections (UTI). The retrospective study included 189 patients who underwent unilateral obstructive upper ureteral stones with concurrent UTI from January 2007 to November 2014 at our institution. Patients received RPLU (81 cases) or UHLL (108 cases). All patients received preoperative anti-infection treatment (indwelling ureteral stent and/or preoperative antibiotics). Collected data, including sex, age, stone size, success rate, operation duration, post-operation hospitalization time, and post-operation complications, were compared. All patients were followed up for more than 6 months after surgeries, and no ureterostenosis occurred. The study included 189 patients, 41 (21.7 %) females and 148 (78.3 %) males with a medium age of 52 years (range 22-81 years). All surgeries were successfully performed without conversion to open surgery. Stone size in the RPLU group was larger than that of the UHLL group (16.1 ± 1.4 vs. 10.4 ± 1.6 mm, P = 0.012). Operative duration (P = 0.009) and hospitalization time (P < 0.001) in the UHLL group were significantly shorter than those in the RPLU group, whereas stone clearance rate was significantly higher in the RPLU group (100 vs. 88.9 %, P = 0.002). Of note, postoperative fever was more common in patients treated with UHLL (15 cases) versus RPLU (4 cases) (13.9 vs. 4.9 %, P = 0.043). Moreover, in the UHLL group, three patients without a preoperative indwelling ureteral stent were complicated with sepsis, which was not seen in RPLU group. In our study, the safety and stone clearance rate of RPLU are better than those of UHLL in the treatment of unilateral upper ureteric calculi with concurrent UTI. Preoperative antibiotics and indwelling ureteral stent may reduce the risk of postoperative infections.

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.

This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.

Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer.

The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients' progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57-4.86, P log-rank = 0.0005] and 2.83 (1.48-5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02-4.78) and 3.32 (1.68-6.55), respectively (P log-rank = 0.0006, P trend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.

Downregulation of homeodomain-interacting protein kinase-2 contributes to bladder cancer metastasis by regulating Wnt signaling.

Homeodomain-interacting protein kinase-2 (Hipk2) has been shown to have important regulatory roles in cancer biology, such as cancer cell proliferation, cell cycle, and cell invasion. However, the contributions of Hipk2 to bladder cancer metastasis remain largely unknown. In the current study, we assayed the expression level of Hipk2 in bladder cancer tissues by real-time PCR, and defined its biological functions. We found that Hipk2 levels were downregulated in most bladder cancer tissues compared with adjacent normal tissues, and Hipk2 levels were remarkably decreased in metastasized tumor tissues when compared with primary tumors. SiRNA-mediated Hipk2 silencing increased bladder cancer cell invasion. Hipk2 knockdown resulted in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression, indicated that epithelial-mesenchymal transition (EMT) was induced. We further demonstrated that Hipk2 knockdown induced Wnt signaling activation and ß-catenin nuclear localization. Finally, we confirmed that Hipk2 inhibition promoted EMT and subsequent cell invasion, at least in part by activating Wnt signaling. These data suggest an important role of Hipk2 in regulating metastasis of bladder cancer and implicate the potential application of Hipk2 in bladder cancer therapy.

Thulium laser resection versus plasmakinetic resection of prostates larger than 80 ml.

PURPOSE: To compare the safety and efficiency of thulium laser resection of the prostate-tangerine technique (TmLRP-TT) and plasmakinetic resection of the prostate (PKRP) for aged symptomatic benign prostatic hyperplasia (BPH) patients with large volume prostates (>80 ml) in a prospective randomized trial with an 18-month follow-up. MATERIALS AND METHODS: From January 2010 to November 2011, 90 BPH patients with large volume prostates were randomized for surgical treatment with TmLRP-TT (n = 45, group 1) or PKRP (n = 45, group 2). The preoperative and postoperative parameters were recorded and compared. All patients were evaluated at 1, 6, 12 and 18 months postoperatively using the International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Q max), postvoid residual urine volume (PVR) and the five-item version of the International Index of Erectile Function score. All perioperative complications were also documented and classified according to the modified Clavien classification system. RESULTS: Compared with the PKRP group, the TmLRP-TT group had a statistically lower hemoglobin drop (0.86 ± 0.42 vs. 1.34 ± 1.04 g/dl, P < 0.01), shorter catheterization time (1.91 ± 0.85 vs. 2.36 ± 0.74 days, P < 0.01) and hospital stay (3.80 ± 0.46 vs. 5.02 ± 0.54 days, P < 0.01). Within the observation period of 18 months, both groups had significant postoperative improvement in IPSS, QoL, Q max and PVR, although no difference was observed between the two groups. Only one patient receiving PKRP treatment required a blood transfusion perioperatively. During the 18-month follow-up, one patient in each group experienced urethral stricture and one patient in the PKRP group experienced bladder neck contracture. Minor complications that required no or noninterventional treatment occurred in 6 (13.33 %) of TmLRP-TT group (Clavien grade 1, 13.33 % and grade 2, 0 %) and 10 (22.22 %) of PKRP group (Clavien grade 1, 20.00 % and grade 2, 2.22 %). No severe complications required reinterventions in both groups (Clavien grade 3, 0 %; grade 4, 0 %; grade 5, 0 %). CONCLUSIONS: Both TmLRP-TT and PKRP are safe and effective treatment options for large prostates that require resection. Taking into account less blood loss, shorter catheterization time and hospital stay, TmLRP-TT may be a better treatment for patients with large prostates.

Expression of Wnt5a during development of anorectal malformations in a rat model of prenatal exposure to di(n-butyl) phthalate.

Mounting evidence has indicated the crucial role of Wnt5a in the embryonic development including guts. However, the Wnt5a involvement in the process of anorectal malformations (ARMs) remains unclear. In this study, we examined the expression of Wnt5a during ARMs development in the offspring of di(n-butyl) phthalate (DBP)-treated pregnant rats. During the neonatal period, Wnt5a expression was evaluated in the terminal rectum of ARM offspring, non-ARM littermates and controls. Using real-time polymerase chain reaction (real-time PCR), western-blot analysis and immunohistochemistry approaches, we found a significant decrease of Wnt5a expression in DBP-induced ARMs rats. Collectively, our results demonstrate the aberrant expression of Wnt5a during anorectal development, which suggests that Wnt5a might be involved in DBP-induced ARMs.

Maternal exposure to Di-n-butyl phthalate (DBP) inhibit orexin receptor 1 (OX1R) expression to prevent Sertoli cells proliferation through the AKT signaling pathway.

BACKGROUND: Studies have demonstrated that Sertoli cells are the direct target of Dibutyl phthalate (DBP). However, the role of neurotransmitter receptors is not elucidated. METHODS: Based on our previous studies, maternal Sprague-Dawley (SD) rats in Gestation Day (GD) 14-18 and TM4 cells exposure to 750 mg/kg/day and 100 µM DBP were regarded as treated groups. Firstly, qRT-PCR array was used to determine the different expression of neurotransmitter receptors. We examined the OX1R expression on Rats in Control and DBP groups by immunohistochemistry. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of OX1R in vivo and in vitro. The potential downstream signaling pathways were explored by analyzing the GSE99690 cohort. In addition, we extracted Primary Sertoli Cells (PSCs) from the testis of control group. The apoptosis-related proteins, AKT signaling pathway-related proteins and mRNA expressions were detected by Western Blot and Real-time PCR in PSCs. The validity of PSCs was measured by CCK-8 assay and flow cytometric analysis was used to demonstrate the apoptotic rates of PSCs after DBP exposure. RESULTS: The Orexin receptor 1 (OX1R) was screened out by qRT-PCR array. Our results showed that DBP could significantly suppress the OX1R expression of Sertoli cells in vivo and in vitro. Functional analysis showed the AKT signaling pathway was mediated by OX1R. The highly expressed apoptosis level and impaired cell activity were observed in PSCs, which can be reversed by Orexin A. Meanwhile, the p-AKT signaling pathway were hindered after DBP exposure while rescued in DBP + Orexin-A group. CONCLUSIONS: DBP can induce Sertoli cell apoptosis through its toxicological effect by suppressing OX1R and p-AKT expression, which provide a novel insight on the role of neurotransmitter receptors.

Prenatal exposure to dibutyl phthalate contributes to erectile dysfunction in offspring male rats by activating the RhoA/ROCK signalling pathway.

Prenatal exposure to dibutyl phthalate (DBP) has been reported to cause erectile dysfunction (ED) in adult offspring rats. However, its underlying mechanisms are not fully understood. Previously, we found that DBP activates the RhoA/ROCK pathway in the male reproductive system. This study investigated how prenatal exposure to DBP activates the RhoA/ROCK signalling pathway, leading to ED in male rat offspring. Pregnant rats were stratified into DBP-exposed and NC groups, with the exposed group receiving 750 milligrams per kilogram per day (mg/kg/day) of DBP through gavage from days 14-18 of gestation. DBP exposure activated the RhoA/ROCK pathway in the penile corpus cavernosum (CC) of descendants, causing smooth muscle cell contraction, fibrosis, and apoptosis, all of which contribute to ED. In vitro experiments confirmed that DBP induces apoptosis and RhoA/ROCK pathway activation in CC smooth muscle cells. Treatment of DBP-exposed offspring with the ROCK inhibitor Y-27632 for 8 weeks significantly improved smooth muscle cell condition, erectile function, and reduced fibrosis. Thus, prenatal DBP exposure induces ED in offspring through RhoA/ROCK pathway activation, and the ROCK inhibitor Y-27632 shows potential as an effective treatment for DBP-induced ED.

Effects of microplastic type on growth and physiology of soil crops: Implications for farmland yield and food quality.

Microplastic residues pose one of the most serious environmental problems in areas where plastic mulch is used extensively. Microplastic pollution has potentially serious consequences for ecosystems and human health. Several studies have analyzed microplastics in greenhouses or laboratory climate-controlled chambers; however, field studies evaluating the effects of different microplastics on different crops in extensive farming are limited. Therefore, we selected three major crops, Zea mays (ZM, monocotyledon), Glycine max (GM, dicotyledon, aboveground-bearing), and Arachis hypogaea (AH, dicotyledon, belowground-bearing) and investigated the effect of adding polyester microplastics (PES-MPs) and polypropylene microplastics (PP-MPs). Our results demonstrate that PP-MPs and PES-MPs decreased the soil bulk density of ZM, GM, and AH. Regarding soil pH, PES-MPs increased the soil pH of AH and ZM, whereas PP-MPs decreased the soil pH of ZM, GM, and AH compared to controls. Intriguingly, different coordinated trait responses to PP-MPs and PES-MPs were observed in all crops. In general, commonly measured parameters of AH, such as plant height, culm diameter, total biomass, root biomass, PSII maximum photochemical quantum yield (Fv/Fm), hundred-gain weight, and soluble sugar tended to decrease under PP-MPs exposure; however, some indicators of ZM and GM increased under PP-MPs exposure. PES-MPs had no obviously adverse influence on the three crops, except for the biomass of GM, and even significantly increased the chlorophyll content of AH, specific leaf area, and soluble sugar of GM. Compared with PES-MPs, PP-MPs have serious negative effects on crop growth and quality, especially AH. The findings of the present study provides evidence for evaluating the impact of soil microplastic pollution on crop yield and quality in farmland and lay a foundation for future investigations on the exploration of MP toxicity mechanisms and adaptability of different crops to microplastics.