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Chao Peng, Jun Zhang, Jianquan Hou Department of Urology, First Affiliated Hospital of Soochow University, Suzhou 215006, China Background: Prognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.Patients and methods: A total of 441 medical records were analyzed, including those of 169 intermediate-risk and 272 high-risk PCa patients. Risk factors for time to BCR were tested and analyzed using Kaplan–Meier survival analysis, log-rank tests, and Cox proportion hazards models.Results: In the intermediate-risk group, prostate-specific antigen density (PSAD) and primary Gleason pattern were significant preoperative risk factors for BCR. Moreover, BCR-free survival of patients in the intermediate-risk group with a higher PSAD (>0.5 ng/mL/cm3) was comparable with that of patients in the high-risk group (P=0.735). When combining primary Gleason pattern 4 and 3 with PSAD cut-offs 0.3–0.7 ng/mL/cm3, we found that BCR-free survival of patients in the intermediate-risk group with a primary Gleason pattern 4 and PSAD >0.3 ng/mL/cm3 was comparable with that of patients in the high-risk group (P=0.463).Conclusion: PSAD and primary Gleason pattern are potential risk factors associated with biochemical failure in intermediate-risk PCa patients after radical prostatectomy. Regarding significant differences in prognosis according to PSAD as well as primary Gleason pattern on biopsy, a subset of the intermediate-risk patients could be identified with outcomes that were equivalent to that of high-risk patients. Keywords: biochemical recurrence, Gleason grade, intermediate risk, prostate cancer, PSA density

Chenchao Zhou,* Jun Zhang,* Ye Chen, Hao Wang, Jianquan Hou Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Background: Interleukin (IL)-35 is a novel inhibitory cytokine and has recently been implicated in tumor immunity. However, the role of IL-35 in prostate cancer (PCa) has not been elucidated.Objective: To evaluate the role of plasma IL-35 in the diagnosis and prognosis of PCa in Chinese patients undergoing initial prostate biopsy.Materials and methods: Using ELISA, plasma IL-35 levels were measured in 180 patients, who underwent a prostate biopsy. The clinical correlation of IL-35 with clinicopathological parameters was also evaluated. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analysis were performed to establish the role of IL-35 as a clinical biomarker.Results: Seventy-five (41.6%) of patients were histopathologically confirmed to have PCa. Plasma IL-35 levels were significantly higher in PCa patients (134.48±78.48 pg/mL) compared to non-PCa patients (67.22±24.08 pg/mL). ROC analysis showed that IL-35 was an independent predictor of PCa. Furthermore, IL-35 was found to be a significantly independent predictor of PCa in a group of patients with prostate-specific antigen levels between 4 and 10 ng/mL; was also able to predict advanced PCa from localized PCa and bone metastasis positive PCa from negative PCa.Conclusion: Our data suggest for the first time that plasma IL-35 levels are correlated with PCa and is the independent predictor of PCa progression and metastasis. Thus, IL-35 could be utilized as a potential biomarker for diagnosis and prognosis of PCa, could also aid in decision making and predict the stage of the disease. Keywords: IL-35, prostate cancer, prostate biopsy, diagnosis

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Purpose: This study aimed to assess the importance of computed tomography (CT) imaging in the diagnostic and prognostic evaluation of renal epithelioid angiomyolipoma (EAML)., Materials and Methods: This study comprised 63 patients diagnosed with renal EAML in the First Affiliated Hospital of Soochow University during 2010-2021, who met the inclusion criteria. The clinical, pathological, and therapeutic features were analyzed to determine the optimum diagnostic and therapeutic approaches., Results: Of the 63 participants, 20 were men and 43 women aged 24-74 years (average, 45.5 years). In 35 and 28 participants, the tumor was located on the left and right sides, respectively. All the patients underwent CT scanning. Most of the patients (54/63) with EAMLs demonstrated hyperattenuation, one showed isoattenuation, and eight showed hypoattenuation compared with renal parenchyma on unenhanced CT images. The diameter of each tumor was 2-25 cm (average, 5.6 cm). All the participants underwent surgical treatment. Of these, 53 were followed up for 4-128 months (median, 64 months). Among the followed-up patients, one died of the tumor, one died due to acute severe pancreatitis, and two had an ipsilateral recurrence., Conclusion: EAML is a relatively rare renal angiomyolipoma depleted in fat. A characteristic of hyperattenuation on unenhanced CT images in EAML can help distinguish this tumor from clear cell renal cell carcinoma. Surgical resection is the main treatment. Most EAMLs are benign, and only a few have malignant potential. However, post-surgery recurrence and metastasis may occur, especially in elderly patients, and thus close follow-up is recommended.

The major antioxidant L-ascorbic acid (AsA) plays important roles in plant growth, development, and stress responses. However, the importance of AsA concentration and the regulation of AsA metabolism in plant reproduction remain unclear. In Arabidopsis (Arabidopsis thaliana) anthers, the tapetum monolayer undergoes cell differentiation to support pollen development. Here, we report that a transcription factor, DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1), inhibits tapetal cell division leading to cell differentiation. We identified SKEWED5-SIMILAR 18 (SKS18) as a downstream target of TDF1. Enzymatic assays showed that SKS18, annotated as a multicopper oxidase-like protein, has ascorbate oxidase activity, leading to AsA oxidation. We also show that VITAMIN C DEFECTIVE1 (VTC1), an AsA biosynthetic enzyme, is negatively controlled by TDF1 to maintain proper AsA contents. Consistently, either knockout of SKS18 or VTC1 overexpression raised AsA concentrations, resulting in extra tapetal cells, while SKS18 overexpression in tdf1 or the vtc1-3 tdf1 double mutant mitigated their defective tapetum. We observed that high AsA concentrations caused lower accumulation of reactive oxygen species (ROS) in tapetal cells. Overexpression of ROS scavenging genes in tapetum restored excess cell divisions. Thus, our findings demonstrate that TDF1-regulated AsA balances cell division and cell differentiation in the tapetum through governing ROS homeostasis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes., Method: The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections., Results: The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable., Conclusion: We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Li, Xie, Liu, Zhuang, Wu, Wu, Sun, Qu, Miao, Zhong, Huang, Yuan, Zhang, Zhang and Hou.)

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies., Competing Interests: None

Appropriate and effective recycling of food waste (FW) has become increasingly significant with the promotion of garbage classification in China. In this study, a novel and green process was developed to recycle FW to prepare a biodegradable composite liquid mulching film (LMF) through crosslinking with sodium alginate (SA). The solid phase of FW was obtained as the raw material after hydrothermal pretreatment to remove pathogens and salts, and to improve the reactivity of active components at a moderate temperature. The prepared LMF had a hydrophobic surface and compact structure due to the lipid in FW and the acetalization reaction and hydrogen bonds among SA, glutaraldehyde and multi-active components of FW, resulting in enhanced water vapor barrier properties. The minimum water vapor permeability of the prepared LMF reached (8.23 ± 0.05) ✕ 10 -12  g cm/(cm 2 ·s·Pa) with 1.82 wt % of plasticizer, 0.74 wt% of crosslinker and a mass ratio of HTP-FW to SA of 3.56:1. The prepared LMF showed good mechanical properties and could maintain its integrity after spraying it on the soil surface for 31 days. In addition, it could effectively prevent the loss of soil moisture and heat, promote the seed germination of Chinese cabbage and achieve 89.14% of weight loss after burying in the soil for 27 days. This study provides a high value-added route to convert the FW to a hydrophobic LMF with superior properties, which addresses not only the problem of food waste but also the pollution of plastic mulching film., (Copyright © 2022. Published by Elsevier Inc.)

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown., Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant., Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population., Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine., Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30., Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit., Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Upper urinary tract stones are very common in my country, with an incidence of 1% to 5% in the North and an even higher incidence of 5% to 10% in the south. The incidence rate in the south is higher than that in the north, mainly due to the water quality, climate and eating habits of the region. From the perspective of sex, incidence is more likely in males than females. In the high-incidence population, young adults are most prone to stones. Men in the age range of 25 to 40 years are more likely to have stones., Aim: To observe the therapeutic effect of minimally invasive percutaneous nephrolithotomy (mPCNL) on upper urinary tract stones and its influence on the renal function of patients., Methods: Patients with upper urinary tract stones who were treated in our hospital from February 2017 to March 2018 were selected as research subjects and were divided into the PCNL group and the mPCNL group according to the random number table method. The general conditions of the two groups of patients were observed during the perioperative period, and the differences in stone clearance, pain, renal function indicators and complication rates were compared between the two groups to determine which were statistically significant ( P < 0.05)., Results: The operation time of the mPCNL group was longer than that of the PCNL group ( t = -34.392, P < 0.001), and the intraoperative blood loss of the mPCNL group was more than that of the PCNL group ( t = 34.090, P < 0.001). There was no difference in renal function indices between the two groups of patients before treatment, and there was no difference in the levels of serum creatinine, β2 microglobulin or retinol binding protein in the mPCNL group after treatment. The visual analog scale score of patients in the mPCNL group was lower than that of the PCNL group ( t = 12.191, P < 0.001), and there was no significant difference in the stone clearance rate between the two groups ( χ 2 value = 1.013, P = 0.314). There was no significant difference in the incidence of urine extravasation, dyspnea and peripheral organ damage between the two groups ( χ 2 value = 1.053, P = 0.305). At 1 mo after treatment and 3 mo after treatment, the quality of life of the mPCNL group was lower than that of the PCNL group, and the Qmax level of the mPCNL group was higher than that of the PCNL group., Conclusion: mPCNL has a good therapeutic effect on upper urinary tract stones, with a high stone clearance rate without causing kidney damage or increasing the incidence of complications, and thus has good application value., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Circular RNAs (circRNAs), emerging as a new type of non-coding RNAs, play important roles in cancers. Instead, the functions and mechanisms of circ&#95;0011385 in cervical cancer (CC) are still inconclusive. Microarray data GSE102686 was downloaded from Gene Expression Omnibus (GEO) database, and were utilized to screen out circRNAs differently expressed in CC tissues. Circ&#95;0011385, miR-149-5p, SRY-box transcription factor 4 (SOX4) mRNA expressions in CC tissues and cells were probed by quantitative real-time PCR (qRT-PCR). CC cell lines with circ&#95;0011385 knockdown were constructed, and he multiplication, migration, invasion, and apoptosis of CC cells were evaluated by cell counting kit-8 (CCK-8) method, transwell assay, and flow cytometry. In addition, the targeting relationships between miR-149-5p and circ&#95;0011385 or SOX4 mRNA 3'UTR were probed by dual-luciferase reporter gene assay and RNA pull-down assay. The regulatory function of circ&#95;0011385 and miR-149-5p on SOX4 expression was studied with western blot. Expressions of circ&#95;0011385 and SOX4 mRNA were raised in CC tissues and cells, while miR-149-5p expression was decreased. Knocking down circ&#95;0011385 restrained the multiplication, migration, and invasion of CC cells and induced the apoptosis. Circ&#95;0011385 directly targeted miR-149-5p, and SOX4 was the target of miR-149-5p, which could be positively regulated by circ&#95;0011385. Circ&#95;0011385 elevates SOX4 expression by targeting miR-149-5p, thus participating in promoting the malignant biological behaviors of CC cells., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC 50 = 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC 50 = 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.

A small-sized c-MYC promoter G-quadruplex selective fluorescent BZT-Indolium binding ligand was demonstrated for the first time as a highly target-specific and photostable probe for in vitro staining and live cell imaging and it was found to be able to inhibit the amplification of the c-MYC G-rich sequence (G-quadruplex) and down-regulate oncogene c-MYC expression in human cancer cells (HeLa).

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis, by H. Liu, J.-K. Chang, J.-Q. Hou, Z.-H. Zhao, L.-D. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (14): 3193-3199-PMID: 28770966" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13140.

Primary Sjögren's syndrome is a chronic autoimmune disease that can lead to systemic manifestations. At present, immunomodulatory agents have not shown good efficacy, many patients in China seek Chinese medicine treatment. Chinese medicine can comprehensively improve the symptoms of patients through Chinese pattern diagnosis and individualized treatment. Fundamental researches are providing scientific bases for the therapeutic effect of Chinese medicine. Professional Chinese medicine treatment can be integrated into the conventional management of primary Sjögren's syndrome.

Purpose: Laparoscopy surgery is the gold standard for the treatment of aldosterone-producing adenomas (APA). However, the effectiveness between laparoscopic total and partial adrenalectomy is controversial. Therefore, we retrospectively analyzed the postoperative and follow-up outcomes of these two procedures., Materials and Methods: A total of 96 APA patients underwent laparoscopic surgery in our hospital between January 2012 and December 2017. A total of 65 patients who underwent laparoscopic partial adrenalectomy (group 1) were compared with 31 patients who underwent laparoscopic total adrenalectomy (group 2). The mean follow-up time was 32.3 months and 40.8 months, respectively. Patient's preoperative characteristics, date during surgery, and postoperative clinical results of the two groups were analyzed., Results: In both groups of patients, laparoscopic adrenalectomy was successfully carried out. The laparoscopic partial adrenalectomy group had a shorter operation time when compared to total adrenalectomy (P = .01). However, patients in the laparoscopic total adrenalectomy group were older (P = .04) and had a higher proportion of multiple adenomas (P = .01) compared to partial adrenalectomy. Five patients (7.7%) who underwent partial adrenalectomy did not show improvement in hypertension and/or serum potassium below normal levels, and review of plasma aldosterone concentration (PAC) and/or computerized tomography (CT) indicated that surgery was not successful in these patients. All 31 patients who underwent total adrenalectomy showed improvement or recovery from hypertension, and all PAC and serum potassium levels returned to normal levels after surgery., Conclusion: Although both surgical procedures were technically safe and feasible, laparoscopic partial adrenalectomy showed a higher failure rate (7.7%) for patients with APA. Therefore, choosing laparoscopic partial adrenalectomy requires careful consideration, and we selected laparoscopic total adrenalectomy in patients with unilateral APA.

Pollen wall consists of several complex layers which form elaborate species-specific patterns. In Arabidopsis, the transcription factor ABORTED MICROSPORE (AMS) is a master regulator of exine formation, and another transcription factor, TRANSPOSABLE ELEMENT SILENCING VIA AT-HOOK (TEK), specifies formation of the nexine layer. However, knowledge regarding the temporal regulatory roles of TEK in pollen wall development is limited. Here, TEK-GFP driven by the AMS promoter was prematurely expressed in the tapetal nuclei, leading to complete male sterility in the pAMS:TEK-GFP (pat) transgenic lines with the wild-type background. Cytological observations in the pat anthers showed impaired callose synthesis and aberrant exine patterning. CALLOSE SYNTHASE5 (CalS5) is required for callose synthesis, and expression of CalS5 in pat plants was significantly reduced. We demonstrated that TEK negatively regulates CalS5 expression after the tetrad stage in wild-type anthers and further discovered that premature TEK-GFP in pat directly represses CalS5 expression through histone modification. Our findings show that TEK flexibly mediates its different functions via different temporal regulation, revealing that the temporal regulation of TEK is essential for exine patterning. Moreover, the result that the repression of CalS5 by TEK after the tetrad stage coincides with the timing of callose wall dissolution suggests that tapetum utilizes temporal regulation of genes to stop callose wall synthesis, which, together with the activation of callase activity, achieves microspore release and pollen wall patterning., Competing Interests: The authors have declared that no competing interests exist.

Autism spectrum disorder (ASD) is a developmental disability which may cause significant social, communication, and behavioral challenges. Besides certain essential symptoms, a lot of ASD individuals also suffer the comorbidity of gut microbiota dysbiosis, which possibly causes a variety of gastrointestinal (GI) difficulties. Interestingly, evidence has indicated that behavioral output may be modulated through the communication between the central nervous system and gut microbiota via the gut-brain axis. Polyunsaturated fatty acids (PUFAs) and n-3 fatty acids (n-3 PUFA) are structurally and functionally crucial components for the brain, and the state of n-3 PUFAs also affects the gut microbiota. However, how varying intake ratios of n-3/n6 PUFAs affect the gut microbiota composition in ASDs is not well-understood. Pregnant female Wistar rats with intraperitoneal administration of valproate acid (VPA) at embryonic day (E) 12.5 and their male offspring were grouped and fed three diets: a control chow (VPA group), omega-3 deficient (A group), and n-3/n6 (1:5) diet (B group). The diet of pregnant female Wistar rats with intraperitoneal administration of saline and their male offspring was a control chow (normal group). Microbial composition and species abundance were investigated accordingly by the 16S rRNA gene-based metagenomics analysis on the fecal samples. Results showed that fecal microbial abundance was decreased because of VPA administration in the period of pregnancy, and the changing pattern of gut microbiota was similar to that reported in ASD patients. Furthermore, the n-3/n6 (1:5) diet increased the fecal microbial abundance and decreased the elevated Firmicutes. In conclusion, n-3/n6 PUFAs (1:5) diet supplementation may alter gut microbiota composition in VPA-exposed rats. This study put forward a new strategy for the intervention and treatment of autism by n-3/n-6 PUFAs ratio supplementation intakes., (Copyright © 2020 Wang, Xu, Hou, Li, Xing, Yang, Zhang, Zhang, Li and Li.)

Phytochemical investigation of the aerial parts of Baeckea frutescens resulted in the isolation of three new mono- or sesquiterpene-based meroterpenoids, frutescones S-U (1-3), and one pair of new (±)-5,7-dihydroxy-8-isobutyryl-6-methyldihydroflavonol (4). Their structures and absolute configurations were established by HR-ESI-MS, 1D and 2D NMR, and quantum chemical ECD calculation. Compound 1 exhibited inhibitory effect on NO production in LPS-activated RAW 264.7 macrophages with an IC 50 value being 0.81 μmol·L -1 ., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Temperature-sensitive genic male sterility (TGMS) lines are widely used in the breeding of hybrid crops 1,2 , but by what means temperature as a general environmental factor reverses the fertility of different TGMS lines remains unknown. Here, we identified an Arabidopsis TGMS line named reversible male sterile (rvms) that is fertile at low temperature (17 °C) and encodes a GDSL lipase. Cytological observations and statistical analysis showed that low temperature slows pollen development. Further screening of restorers of rvms, as well as crossing with a slow-growth line at normal temperature (24 °C), demonstrate that slowing of development overcomes the defects of rvms microspores and allows them to develop into functional pollen. Several other Arabidopsis TGMS lines were identified, and their fertility was also restored by slowing of development. Given that male reproductive development is conserved 3 , we propose that slowing of development is a general mechanism applicable to the sterility-fertility conversion of TGMS lines from different plant species.

Background/objectives: Sjogren - Larsson syndrome (SLS) is a rare autosomal recessive disease of the mutation ALDH3A2 that identifies a part of fatty acids for fatty aldehyde dehydrogenase: NAD-oxidoreductase enzyme complex. This study aimed to access variant ALDH3A2 gene coded for FALDH and products regulating pathogenic melanogenesis owing to increased oxidative stress and reactive oxygen species resulting in DNA harm in SLS. By turning them into fatty acids, FALDH avoids the accumulation of toxic fatty aldehydes. The mutation results in the accumulation of aldehyde-modified lipids or fatty alcohols that may interfere with skin and brain function., Methods: In Nov 2018, we performed a literature search in PubMed for clinical studies, clinical trials, case reports, controlled trials, randomized controlled trials, and systemic reviews. The search terms we used were "SJOGREN-LARSSON SYNDROME" AND "HYPERMELANNOSIS" OR "FALDH" (from 1985). The search resulted in 1,289 articles, out of these 95 articles met our inclusion exclusion criteria. Our inclusion criteria included relevant original articles relevant, critical systemic reviews, and crucial referenced articles, ex-clusion criteria included duplicates and articles not published in English language., Results: Toxicity of long-chain aldehydes to FALDH-deficient cells owing to accumulation under the profound epidermis layer improves oxidative stress in the cell resulting in keratinocyte hyperproliferation., Conclusion: While it continues to be determined whether accumulated fatty alcohol and fatty aldehydes obtained from ether glycerolipids and sphingolipids improve the susceptibility of melanocytes and their element accountable for skin hyperpigmentation to biological colour., (© 2019 Wiley Periodicals, Inc.)

Biomimetic total syntheses of baefrutones A-D (1-4), baeckenon B (5), and frutescones A, D-F (6-9), isolated from the leaves of Baeckea frutescens, were achieved in 9, 8, and 5 steps, respectively, in moderate to good yields (72-83%). The synthetic routes feature the Michael addition, oxidative [4 + 2] cycloaddition, and water-promoted Diels-Alder click reactions as the key steps. This study helped gain thorough mechanistic insights into the biosynthetic origins and provided a facile approach for the construction of a library of natural tasmanone-based meroterpenoid analogues. Moreover, compounds 1-9 show potent inhibitory effects against S. paratyphi and/or C. albicans with MIC values of 3.125-25 μg mL -1 , and they could be promising lead molecules for the design of new antibiotic agents.

Psiguadiols A-J ( 1 - 10 ), new meroterpenoids with rearranged skeletons, were isolated from the leaves of Psidium guajava . Compounds 1 - 3 represent the first examples of 6,8-diformyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids with an unprecedented C-8-spiro-fused 6/6/9/4 tetracyclic ring system. Compounds 4 and 5 represent two unusual scaffolds featuring 1β,6β- and 3α,5α-epoxy rings, respectively. The combination of spectroscopic data analyses, comparison of experimental and calculated ECD data, and single-crystal X-ray diffraction data of 1 , 6 , and 8 allowed for the assignment of the structures. A putative biosynthetic pathway for 1 - 10 is discussed. Compounds 1 , 7 , and 8 exhibited inhibitory activities against PTP1B with IC 50 values of 4.7, 6.2, and 9.2 μM, respectively. In addition, molecular docking was performed to investigate the mechanism of action.

Objective: To clarify the effect of FOXR2 on the proliferation and apoptosis of prostate cancer cells and to reveal the mechanism. Methods: The expression of FOXR2 in clinical samples of prostate cancer were detected by Quantitative Real-time PCR (qRT-PCR) and Western blotting. The CCK8 proliferation kit and the Annexin V-FITC apoptosis kit, flow cytometry were used to detect the proliferation and apoptosis of prostate cancer cells with or without the FOXR2 knockdown. Combined with the results of microRNA chip, we predicted the related miR-152 and detected the relationship between miR-152 and FOXR2 by luciferase reporter gene assay. The correlation between HOTAIR and miR-152 is clearly defined by software prediction and qRT-PCR. Results: FOXR2 had a relatively high expression in the prostate cancer tissue.The mRNA expression of FOXR2 is 4.9 times that of adjacent tissues, and the protein level was also significantly up-regulated. In the PC3 cell line, the specific knock-down of FOXR2 inhibits the proliferation of cells and promotes cell apoptosis. According to the microRNA chip results and luciferase reporter gene assay, we found miR-152 could regulate the expression of FOXR2; and FOXR2 3 'UTR had two miR-152 binding sites, all of which could control the expression of FOXR2. The results of LNCediting and qRT-PCR suggest that HOTAIR is negatively correlated with the expression of miR-152, and is involved in the regulation of miR-152 expression in prostate cancer. Conclusion: FOXR2 up-regulation can promote the proliferation and inhibit the apoptosis of prostate cancer cells because that HOTAIR restrains the expression of miR-152.

Five new phloroglucinol derivatives, eucalyptins C-G (1-5), together with 13 known analogues (6-18) were isolated from the fruits of Eucalyptus globulus. The structures and absolute configurations of 1-5 were established by means of spectroscopic data analysis, computational calculation methods, and single-crystal X-ray diffraction. Compounds 1-18 were investigated for their immunosuppressive effects in vitro, and 1, 2, 6, and 7 displayed moderate inhibitory activities with IC 50 values of 11.8, 10.2, 18.2, and 19.1 μM, respectively. The stimulation index (SI) of 1 was 64.2 and was compared to that of cyclosporine A (SI = 149.57). Further study demonstrated that 1 exhibited an immunosuppressive effect through inducing apoptosis and inhibiting cytokine secretion.

What Is Known and Objective: Aristolochic acid (AA) is an abundant compound in Aristolochia plants and various natural herbs. In the 1990s, a slimming formula used in Belgium that contains Aristolochia fangchi was reported to cause kidney damage and bladder cancer, and aristolochic acid nephropathy (AAN) is now well recognized worldwide. In October 2017, researchers reported an AA signature that is closely associated with hepatocellular carcinoma (HCC) worldwide., Comment: There are differing opinions on the toxicity of AA, and different countries have taken different measures to address the issue. There is a lack of clarity on the causal role of AA in hepatocarcinogenesis and on the potential underlying mechanisms for the reported nephrotoxicity and carcinogenicity. The toxicity of AA differs depending on gender and age, and other risk factors that could explain the variability in the toxicity of AA remain to be identified., What Is New and Conclusion: Whether preparations containing AA, such as many Chinese medicines, should be used remains controversial, and this issue warrants further investigation before definite conclusions can be drawn., (© 2018 John Wiley & Sons Ltd.)

Glycogen synthase kinase-3β (GSK-3β) is a key enzyme in hyperphosphorylation of tau proteins and is a promising therapeutic target in Alzheimer's disease (AD). Here, we reported, for the first time, that the stereoisomers of Schisandrin B (Sch B), (+)-1, (-)-1, (+)-2, and (-)-2, were potent GSK-3β inhibitors. They were demonstrated to selectively target GSK-3β in an orthosteric binding mode, with IC 50 values of 340, 290, 80, and 70 nM, respectively. Further study showed that these stereoisomers can significantly increase the expression of p-GSK-3β (Ser9) and decrease the expressions of p-GSK-3β (Tyr216) and p-GSK-3β (Tyr279). Finally, these compounds can alleviate the cell injury induced by Aβ, and the cognitive disorders in AD mice, especially (+)-2 and (-)-2. Collectively, the stereoisomers of Sch B, especially (+)-2 and (-)-2, were found to be potential selective ATP-competitive GSK-3β inhibitors, which further affected their anti-AD effects. These promising findings explained the biological target of Sch B in AD, and bring a new understanding in the stereochemistry and bioactivities of Sch B.

Baefrutones A-F (1-6), six new meroterpenoids with rare triketone-phloroglucinol-monoterpene/sesquiterpene frameworks, together with their biosynthetically related intermediate (±)-baeckenon B (7), were isolated from the aerial part of Baeckea frutescens under the guidance of HPLC-Q/TOF-MS2 investigation. Compounds 1-4 represent the first examples of natural meroterpenoids existing as four pairs of inseparable diastereomeric atropisomers (2 : 1, 1H NMR integration) caused by the restricted rotation around the C-6-C-7-C-1' bonds arising from the intramolecular hydrogen bond between C-1 carbonyl and 2'-OH. The discovery of these architectures not only largely enriched the chemodiversity of the meroterpenoid and atropisomer library, but also might be exciting and challenging for asymmetric organic synthesis. Their structures and absolute configurations were established by extensive spectroscopic analysis, X-ray diffraction, and ECD calculations. Compounds 5 and 6 were biomimetically synthesized from 7 and β-caryophyllene via a regioselective oxidative hetero-Diels-Alder reaction, thus providing access to the construction of the 6/6/9/4 tetracyclic ring system. The anti-inflammatory activities of these meroterpenoids were also discussed.

Purpose: To explore the neuroprotective effects and its possible mechanisms of melatonin (MT) on erectile dysfunction in streptozotocin-induced diabetic rats., Methods: Twenty-eight Sprague-Dawley rats received intraperitoneal injection of streptozotocin and 8 weeks later, the determined diabetic rats randomly got intraperitoneal injection of phosphate buffer solution (PBS) or MT. Another 12 normal rats received PBS treatment. Four weeks later, intracavernous pressure, mean arterial pressure, pathological changes in penis, and major pelvic ganglion (MPG) were measured. Malondialdehyde, superoxide dismutase, p38 and p-p38 levels in penis were detected., Results: Diabetic rats showed significant decreases of erectile function accompanied with serious neuropathy in dorsal penile nerve (DPN) and MPG, meanwhile collagen deposition, oxidative stress, and p-p38 levels in penis were elevated. Melatonin treatment partially but significantly improved the erectile function, ameliorated neuropathy in DPN and MPG, and decreased collagen deposition, oxidative stress, and p-p38 levels in diabetic rats., Conclusions: Melatonin treatment helps improve erectile function and ameliorate neuropathy and fibrosis in diabetic rats. These may be associated with reductions in oxidative stress, p38MAPK signaling pathway, and neuropathy.

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC 50 values ranging from 1.95 to 5.54 μmol·L -1 and ranging from 1.01 to 2.27 μmol·L -1 , respectively., (Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

A symmetric ligand is synthesized composed of a core N -methylpyridinium scaffold and two para -substituted benzyl groups through a flexible ethylene bridge to form a novel three-ring-conjugated system. The ligand system was found to have only weak background fluorescent signal in aqueous or physiological conditions and exhibited strong fluorescent signal enhancement targeting at telo21 G-quadruplex structure rather than other types of nucleic acids. The comparison study with two terminal groups (-N(CH 3 ) 2 versus -SCH 3 ) indicates that the stimulated signal enhancement of specific binding is probably attributed to the hydrogen-bonding interactions through the amino groups in the G-quartets. The docking result illuminates the experimental observation that the ligand system showed only weak fluorescent signals in aqueous or physiological conditions while exhibiting a strong fluorescent signal upon binding to the telo21 G-quadruplex structure (binding energy: -6.2 kcal mol -1 )., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We have developed an incandescent Mo source to fabricate large-area single-crystalline MoSe 2 thin films. The as-grown MoSe 2 thin films were characterized using transmission electron microscopy, energy dispersive x-ray spectroscopy, atomic force microscopy, Raman spectroscopy, photoluminescence (PL), reflection high energy electron diffraction (RHEED) and angular resolved photoemission spectroscopy (ARPES). A new Raman characteristic peak at 1591 cm -1 was identified. Results from Raman spectroscopy, PL, RHEED and ARPES studies consistently reveal that large-area single crystalline mono-layer of MoSe 2 could be achieved by this technique. This technique enjoys several advantages over conventional approaches and could be extended to the growth of other two-dimensional layered materials containing a low-vapor-pressure element.

Frutescones H-R (1-11), new sesqui- or monoterpene-based meroterpenoids, were isolated from the aerial parts of Baeckea frutescens. Their structures and absolute configurations were established by means of spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ECD), as well as single-crystal X-ray crystallography of 1, (-)-7, and 9. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages, and the structure-activity relationships of 1-11 are also discussed. Compound 8 exhibited anti-inflammatory activity with an IC 50 value of 0.36 μM, which might be related to the regulation of the NF-κB signaling pathway via the suppression of p65 nuclear translocation and the consequent decrease of IL-6 and TNF-α.

Objective: Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway participate in cell proliferation and apoptosis. Suppressors of cytokine signaling 3 (SOCS3) are negative regulators of JAK-STAT3. SOCS3 was found significantly declined, while microRNA-221 (miR-221) obviously up-regulated in bladder cancer tissue. Bioinformatics analysis revealed the complementary binding site between miR-221 and 3'-UTR of SOCS3. This study investigated the role of miR-221 in regulating SOCS3/JAK-STAT3 signaling pathway and bladder cancer cell proliferation and apoptosis., Patients and Methods: Bladder cancer tumor tissue and para-carcinoma tissue were collected from patients to test miR-221 and SOCS3 expressions. Dual luciferase assay was used to test the targeting regulatory effect of miR-221 on SOCS3. MiR-221, SOCS3, p-JAK1, p-JAK2, and survivin expressions were compared in T24 and HBEC cells. T24 cells were divided into miR-NC, miR-221 inhibitor, pSicoR-blank, pSicoR-SOCS3, and miR-221 inhibitor + pSicoR-SOCS3 groups. Flow cytometry was applied to detect cell apoptosis. EdU staining was adopted to evaluate cell proliferation., Results: MiR-221 significantly increased, while SOCS3 obviously reduced in bladder cancer tissue compared with para-carcinoma tissue. MiR-221 targeted inhibited SOCS3 expression. MiR-221, phosphorylated JAK1 (p-JAK1), phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), and survivin levels markedly up-regulated, whereas SOCS3 expression apparently declined in T24 cells compared with that in HBEC cells. MiR-221 inhibitor and/or pSicoR-SOCS3 elevated SOCS3 expression, decreased p-JAK1, p-JAK2, p-STAT3, and survivin levels, enhanced cell apoptosis, and attenuated cell proliferation., Conclusions: MiR-221 elevated, while SOCS3 reduced in bladder cancer tissue. Inhibition of miR-221 suppressed T24 cell proliferation and induced apoptosis by up-regulating SOCS3 expression, lowering JAK-STAT3 signaling pathway activity, and attenuating survivin expression.

The present study was designed to investigate the chemical constituents of the roots of Cyathula officinalis. Compounds were isolated by silica gel, Sephadex LH-20, ODS column chromatography, and preparative HPLC. Their structures were determined on the basis of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. One new oleanane-type triterpenoid saponin, 28-O-[α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranosyl-(1→3)-β-D-glucopyranosyl] hederagenin (1), was isolated from the roots of Cyathula officinalis. The anti-inflammatory activities of the isolates were evaluated for their inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages cells. Compounds 2, 4, and 6 exhibited moderate anti-inflammatory activities., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Frutescone A-G [(1-6), (+)-7, (-)-7], a new group of naturally occurring tasmanone-based meroterpenoids, were isolated from the aerial parts of Baeckea frutescens L. Compounds 1 and 4 featured a rare carbon skeleton with an unprecedented oxa-spiro[5.8] tetradecadiene ring system, existing as two favored equilibrating conformers in CDCl 3 solution, identified by variable-temperature NMR. The regioselective syntheses of 4-7 were achieved in a concise manner by a biomimetically inspired key hetero-Diels-Alder reaction "on water". Compounds 1, 4, and 5 exhibited moderate cytotoxicities in vitro.

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg-1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

Objective: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS)., Methods: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups., Results: Patient preoperative variables were comparable between the two groups, with no significant difference ( P  > 0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group ( P  = 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P  = 0.010). The stone-free rates after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively ( P  = 0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7% (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up ( P  = 0.175); the rates of complications in the 2 groups were 19.0% (4/21) and 13.3% (2/15), respectively ( P  = 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group ( P  = 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group; however, the distributions in the F-URS group were 46.7% (7/15) and 53.3% (8/15), respectively ( P  = 0.310)., Conclusion: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.

Objective: To investigate the effects of cynomorium songaricum (CS) decoction on the testis weight, serum testosterone level, and sperm parameters of rats with oligoasthenospermia (OAS), explore its action mechanism of improving the proliferation of undifferentiated spermatogonial cells, and provide some experimental and theoretical evidence for the development of new Chinese drugs for OAS., Methods: Thirty 8-week-old male SD rats were randomly divided into five groups of equal number: blank control, model control, high-dose CS, medium-dose CS, and low-dose CS. OAS models were established by intraperitoneal injection of cyclophosphamide and, a month later, treated intragastrically with normal saline or CS at 2, 1, and 0.5 g per kg of the body weight per day, all for 4 weeks. Then, the testes of the animals were harvested to obtain the testicular weight, sperm concentration and motility, and the level of serum testosterone (T), detect the expressions of the transcription factor 1 (Oct4), Thy-1 cell surface antigen (Thy1), promyelocytic leukemia zinc finger (PLZF), KIT proto-oncogene receptor tyrosine kinase (C-kit) and glial cell-derived neurotrophic factor (GDNF) in the testis tissue of the rats in the low-dose CS group by real-time PCR., Results: The testis weights in the blank control, model control, high-dose CS, medium-dose CS, and low-dose CS groups were (1.52±0.06), (1.55±0.06), (1.43±0.30), (1.35±0.40) and (1.34±0.04) g, respectively, not significantly different in the blank and model controls from those in the CS groups (P>0.05). The visual field sperm count per 10 HP was significantly increased in the high-, medium-, and low-dose CS groups (202±20, 196±5 and 216±25) as compared with the blank and model controls (200±15 and 134±30) (P<0.05). The mRNA expressions of the Oct4, Thy1, PLZF and GDNF genes were remarkably higher in the low-dose CS group than in the controls (P<0.05), but that of the C-kit gene showed no significant difference from the latter (P>0.05). The visual field sperm motility per 10 HP was markedly increased in the blank control (［52.1±5.5］%), model control (［38.1±2.5］%), high-dose CS (［59.1±9.5］%), medium-dose CS (［58.7±9.5］%), and low-dose CS (［49.6±1.0］%) groups, and so was the level of serum testosterone (［190±87.5］, ［82.5±25.8］, ［229±75.6］, ［331±86.7］ and ［185±82.4］ mmol/L), both remarkably higher in the CS groups than in the model controls (P<0.05) but with no statistically significant difference between the CS groups and the blank controls (P>0.05)., Conclusions: CS can significantly improve sperm concentration, sperm motility and serum T level in OAS rats, probably by inducing the expression of GDNF in the rat Sertoli cells, promoting the proliferation of undifferentiated spermatogonial cells, and enhancing spermatogenesis.

Background: The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy., Methods: Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection., Results: PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. -1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P< 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03)., Conclusions: Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.

The universal fluorescent staining property of thiazole orange (TO) dye was adapted in order to be specific for G-quadruplex DNA structures, through the introduction of a styrene-like substituent at the ortho-position of the TO scaffold. This extraordinary outcome was determined from experimental studies and further explored through molecular docking studies. The molecular docking studies help understand how such a small substituent leads to remarkable fluorescent signal discrimination between G-quadruplex DNA and other types of nucleic acids. The results reveal that the modified dyes bind to the G-quadruplex or duplex DNA in a similar fashion as TO, but exhibit either enhanced or quenched fluorescent signal, which is determined by the spatial length and orientation of the substituent and has never been known. The new fluorescent dye modified with a p-(dimethylamino)styryl substituent offers 10-fold more selectivity toward telomeric G-quadruplexes than double-stranded DNA substrates. In addition, native PAGE experiments, FRET, CD analysis, and live cell imaging were also studied and demonstrated the potential applications of this class of thiazole-orange-based fluorescent probes in bioassays and cell imaging.

Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.

Cryopreservation brings sublethal damage to sperm, resulting in reduced fertile life of sperm. Rhodiola rosea polysaccharides (RPs) have antiviral, antioxidant and antitumor activities. In the present study, the cryoprotective effect of RPs on boar sperm quality parameters after frozen-thawed process was investigated. Boar sperm was cryopreserved in the extender with RPs added at concentrations of 0 (used as control), 2, 4, 6, 8 and 10mg/L and their effects on the quality of frozen-thawed boar sperm were assessed. Addition of RPs significantly improved sperm motility, mitochondrial activity, acrosomal integrity, plasma membrane integrity, superoxide dismutase and glutathione peroxidase activity and decreased sperm malonaldehyde level (p<0.05). The results indicated that the addition of RPs to the freezing extender decreased the cryodamage to the boar sperm., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .

c-MYC is an important oncogene that is considered as an effective target for anticancer therapy. Regulation of this gene's transcription is one avenue for c-MYC-targeting drug design. Direct binding to a transcription factor and generating the intervention of a transcriptional programme appears to be an effective way to modulate gene transcription. NM23-H2 is a transcription factor for c-MYC and is proven to be related to the secondary structures in the promoter. Here, we first screened our small-molecule library for NM23-H2 binders and then sifted through the inhibitors that could target and interfere with the interaction process between NM23-H2 and the guanine-rich promoter sequence of c-MYC. As a result, a quinazolone derivative, SYSU-ID-01: , showed a significant interference effect towards NM23-H2 binding to the guanine-rich promoter DNA sequence. Further analyses of the compound-protein interaction and the protein-DNA interaction provided insight into the mode of action for SYSU-ID-01: . Cellular evaluation results showed that SYSU-ID-01: could abrogate NM23-H2 binding to the c-MYC promoter, resulting in downregulation of c-MYC transcription and dramatically suppressed HeLa cell growth. These findings provide a new way of c-MYC transcriptional control through interfering with NM23-H2 binding to guanine-rich promoter sequences by small molecules., (© Oxford University Press OR Nucleic Acids Research 2015.)

Introduction: long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in urothelial carcinoma of the bladder (UCB) is just beginning to be studied. In this study, we focused on lncRNA SPRY4-IT1 and investigated its expression pattern, clinical significance, and biological function in UCB., Methods: SPRY4-IT1 expression in UCB tissues was examined by quantitative Real-time PCR (qRT-PCR) and its correlation with clinicopathological features and patient prognosis was later analyzed. Moreover, in vitro assays were performed to explore its role in bladder cancer progression., Results: SPRY4-IT1 expression was elevated in UCB tissues, and SPRY4-IT1 levels were highly positively correlated with histological grade, tumor stage, and lymph node metastasis and reduced overall survival. A multivariate analysis showed that SPRY4-IT1 expression is an independent prognostic factor of overall survival in patients with UCB. Additionally, the results of in vitro assays showed that the suppression of SPRY4-IT1 expression in bladder cancer cells significantly inhibit cell proliferation, migration, and invasion., Conclusions: Our data suggested that lncRNA SPRY4-IT1 is a novel molecule involved in bladder cancer progression, which provide a potential prognostic biomarker and therapeutic target.

To efficiently identify small molecules binding to a G-quadruplex structure while avoiding binding to duplex DNA, we performed a multistep structure-based virtual screening by simultaneously taking into account G-quadruplex DNA and duplex DNA. Among the 13 compounds selected, one outstanding ligand shows significant selectivity for G-quadruplex binding as determined using SPR, FRET-based competition and luciferase activity assay.