Iron(II)-Catalyzed Radical [3 + 2] Cyclization of N-Aryl Cyclopropylamines for the Synthesis of Polyfunctionalized Cyclopentylamines.

A facile iron(II)-catalyzed radical [3 + 2] cyclization of N-aryl cyclopropylamines with various alkenes to access the structurally polyfunctionalized cyclopentylamine scaffolds has been developed. Using low-cost FeCl2·4H2O as catalyst, N-aryl cyclopropylamines could be utilized to react with a wide range of alkenes including exocyclic/acyclic terminal alkenes, cycloalkenes, alkenes from the natural-occurring compounds (Alantolactone, Costunolide), and known drugs (Ibuprofen, l-phenylalanine, Flurbiprofen) to obtain a variety of cyclopentylamines fused with different useful motifs in generally good yields and diastereoselectivities. The highlight of this protocol is also featured by no extra oxidant, no base, EtOH as the solvent, gram-scale synthesis, and further diverse transformations of the synthetic products. More importantly, an iron(II)-mediated hydrogen radical dissociation pathway was proposed based on the mechanism research experiments.

Understanding the Transcriptional Changes During Infection of Meloidogyne incognita Eggs by the Egg-Parasitic Fungus Purpureocillium lilacinum.

The egg-pathogenic fungus Purpureocillium lilacinum parasitizes on nematode eggs, and thus, it is used as a good biocontrol agent against plant root-knot nematodes. However, little is known about the transcriptional response of P. lilacinum while infecting nematode eggs. This study presents the whole transcriptome sequencing of P. lilacinum and transcriptome-wide gene expression analysis of P. lilacinum upon infecting the eggs of Meloidogyne incognita compared to non-infecting controls. A transcriptomic library of P. lilacinum was used as reference gene set and six transcriptomic libraries of the non-infecting control and P. lilacinum infecting M. incognita eggs were constructed, respectively, comprising three biological replicates of each. A total of 1,011 differently expressed genes (DEGs) were identified in the infecting samples, including 553 up-regulated and 458 down-regulated genes compared to the non-infecting control samples. Furthermore, functional enrichment analysis exhibited that these DEGs were primarily involved in oxidative phosphorylation, oxidoreductase activity, and metabolic processes. Fifteen DEGs were randomly selected to verify the RNA sequencing results through quantitative real-time polymerase chain reaction (qPCR). The study focused on P. lilacinum genes that were strongly expressed upon infecting M. incognita eggs. These DEGs were primarily involved in detoxification, parasitic behavior, and nutritional utilization. This study contributes significantly to the understanding of the molecular mechanisms underlying the parasitic action of P. lilacinum on nematode eggs and provides a valuable genetic resource for further research on parasitic behavior of P. lilacinum. Notably, this study examined the transcriptomics of P. lilacinum infecting M. incognita eggs at only one time point. Since there were fungi at different stages of the infection process at that time point, the transcriptional profiles are not precisely examining one specific stage in this process.

Nine new dichapetalin-type triterpenoids from the twigs of Dichapetalum gelonioides (Roxb.) Engl.

Nine previously undescribed dichapetalin-type triterpenoids (1-9), along with 12 reported compounds (10-21), were isolated from the twigs of Dichapetalum gelonioides. Their chemical structures were mainly elucidated by comprehensive analysis of HRMS, 1D and 2D NMR spectroscopic data. The absolute configuration of compound 1 was further determined based on single-crystal X-ray diffraction. In addition, a part of compounds were evaluated the effects of inhibitory NO production in LPS-induced RAW264.7 macrophages.

Arg-Gly-Asp Peptide-Functionalized Superparamagnetic γ-Fe2O3 Nanoparticles Enhance Osteoblast Migration In Vitro.

Making osteoblast migration manageably target to injury sites has been the key challenging in cell therapy for bone and cartilage regeneration. Superparamagnetic materials, the magnetic guide for cell migration, have been applied to increase cell retention. However, additional targeting modifications are still needed to accelerate the low uptake efficiency and moving speed. Arg-Gly-Asp peptide (RGD)-functionalized magnetic nanoparticles showed cutting-edge competence in cell differentiation control and targeted drug delivery. However, more evidence was required to corroborate its role in osteoblast migration in bone repair. In the present study, RGD-modified γ-Fe2O3 nanoparticles (RGD-Fe2O3 NPs) were prefabricated with the grafting ratio of 33.3-37.4%. The RGD-Fe2O3 NPs unveiled excellent water dispersibility with uniform size distribution at 5-6 nm and negligibly low cytotoxicity. As a result, MC3T3-E1 osteoblasts treated with RGD-Fe2O3 NPs boosted its migration speed in a magnetic field compared with those incubated with unmodified Fe2O3 NPs. Furthermore, osteoblasts treated with RGD-Fe2O3 NPs exhibited more Fe uptake. The results exposed the fact that RGD-mediated specific cellular uptake presented higher efficiency than the non-RGD-mediated one, resulting from a stronger superparamagnetic force between the labeled cells and the magnetic field. These findings indicate that the RGD-functionalized Fe2O3 NPs can promote osteoblast migration in the magnetic field, providing a promising strategy in magnet-guided cell therapy for bone and cartilage regeneration.

PAQR6 Expression Enhancement Suggests a Worse Prognosis in Prostate Cancer Patients.

OBJECTIVE: This study aimed to evaluate the expression of progestin and adipoQ receptor family member VI (PAQR6, mPRδ) in prostate cancer and to explore its role in prostate cancer progression. METHODS: PAQR6 mRNA expression was evaluated based on the data obtained from the TCGA database and the GEO database. The prognostic value of PAQR6 was explored by Kaplan-Meier analysis. To investigate the role of PAQR6, it was depleted by siRNA in DU145 cells. The effects of depleting PAQR6 on DU145 cell viability and migration were determined by CCK8 assay, colony formation assay, and wound healing assay, respectively. The activation of MEK and ERK were analyzed by western blot. RESULTS: PAQR6 mRNA expression was significantly up-regulated in prostate cancer tissues and correlated with lower survival rates (p=0.014). Furthermore, qPCR revealed that PAQR6 expression was elevated in DU145 and LNCaP cells compared with RWPE-2 cells. Depleting PAQR6 obviously suppressed DU145 cell proliferation and migration (p<0.01). In addition, the ratio of p-MEK/MEK and p-ERK/ERK was significantly reduced after silencing PAQR6 (p<0.01). CONCLUSION: PAQR6 might play a facilitating role in prostate cancer development by regulating the MAPK signaling pathway. Moreover, it might serve as a potential predictor and therapeutic target in prostate cancer.

Two new phenolic glycosides isolated from the fruits of Citrus aurantium.

The present study was designed to investigate the chemical constituents of the fruit of Citrus aurantium L.. The compounds were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Two new phenolic glycosides (compounds 1 and 2) were obtained and identified as 1-O-3, 5-dihydroxyphenyl-(6-O-4-hydroxybenzoyl)-ß-D-glucopyranoside (1) and 1-O-3, 5-dihydroxyphenyl-(6-O-3-methoxy-4-hydroxy benzoyl)-ß-D-glucopyranoside (2), respectively.

[¹H-NMR-based metabonomics on chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet].

To study the chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet based on ¹H-NMR metabonomics. Twenty-four male Wistar rats were divided into four groups： control group, R group (treated with Realgar), RRSPG group (treated with Realgar, the root and rhizoma of Rheum palmatum, the root of Scutellaria baicalensis, the root of Platycodon grandiflorum and the root and rhizoma of Glycyrrhiza uralensis) and RC group (treated with total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis). Based on ¹H-NMR spectra of urine and serum from rats, PLS-DA was performed to identify different metabolic profiles.The metabolic profiles of R group were different from that of control group, while the metabolic profiles of RC group were almost similar to control group.Total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis regulated energy, choline and amino acid metabolism and gut flora disorder affected by realgar's toxicity.

Two new compounds from the metabolites of a marine-derived actinomycete Streptomyces cavourensis YY01-17.

Our current marine natural product program investigated the second metabolites of an actinomycete Streptomyces cavourensis YY01-17 originating from the Antarctic ecological niche to discover potential antitumor chemical entities. Two new compounds, along with a known compound, were isolated from the ethyl acetate extract of the fermentation broth of the marine-derived actinomycete, and their structures were elucidated, respectively, as 2(S)-3'-hydroxybutan-2'-yl 2-hydroxypropanoate (1), (E)-3-hydroxy-2,4-dimethylhept-4-enamide (2), and 2-hydroxy-3-methylbutanoic acid (3) on the basis of spectroscopic data interpretation.

[Transrectal high-intensity focused ultrasound for treatment of benign prostatic hyperplasia: report of 262 cases].

OBJECTIVE: To explore the application of transrectal high-intensity focused ultrasound (HIFU) for treatment of benign prostatic hyperplasia (BPH). METHODS: From Dec. 2002 to Dec. 2006, 262 BPH patients underwent transrectal HIFU ablative therapy. After the treatment, IPSS, QOL score, peak uroflow rate and prostatic volume measured by TRUS were used for evaluation. RESULTS: After 1 to 3 years' follow-up, IPSS, QOL score, and prostatic volume all decreased, while the peak uroflow rate increased obviously (P<0.01). Mild hematuria was noted in all the cases after the treatment, and epididymitis was found in 7 cases (2.7%), short-term hematospermia in 66 cases (25.2%), retrograde ejaculation in 35 cases (13.4%), and urethro-rectal fistula in 1 case (0.3%). No urinary incontinence was found in these cases. TURP was performed in 18 cases (6.8%) in 3 years after the treatment due to an excessively large volume of the prostates or bladder neck contracture. CONCLUSION: HIFU is effective and safe in the treatment of BPH which causes minimal invasion, absence of intraoperative bleeding, good tolerance and few complications, and is especially suitable in elderly patients.

Does a smaller tract in percutaneous nephrolithotomy contribute to less invasiveness? A prospective comparative study.

OBJECTIVES: To determine the systemic response to percutaneous nephrolithotomy (PCNL) and mini-PCNL (MPCNL) and evaluate whether MPCNL is less invasive than PCNL, as experimental studies suggest that the acute-phase reaction is proportional to surgery-induced tissue damage. METHODS: In all, 165 consecutive patients who had undergone MPCNL (93) or PCNL (72) were prospectively assessed. Blood samples were collected 24 hours before; during surgery; at the end of anesthesia; and 12, 24, and 36 hours after surgery. The extent of the systemic response to surgery-induced tissue trauma was measured, by assessing the levels of acute-phase markers tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and serum amyloid A (SAA), at all sampling times in all patients. RESULTS: No significant differences were observed between the 2 groups in preoperative variables. Baseline levels of TNF-alpha, IL-6, IL-10, CRP, and SAA were comparable in both groups. An increase was noted in TNF-alpha, IL-6, CRP, and SAA after surgery but no significant differences were assessed between MPCNL and PCNL during the entire period. IL-10 did not change at the different sampling times. CONCLUSIONS: Our data fail to demonstrate significant advantages of MPCNL in terms of reduced surgical trauma and associated invasiveness compared with standard PCNL based on the variables objectively measured in this study.

Prospective comparison of five mediators of the systemic response after high-intensity focused ultrasound and targeted cryoablation for localized prostate cancer.

OBJECTIVE: To evaluate whether high-intensity focused ultrasound (HIFU) is less invasive than targeted cryoablation of the prostate (TCAP), as experimental studies suggest that the acute-phase reaction is proportional to surgery-induced tissue damage. PATIENTS AND METHODS: Between May 2004 and December 2007, 127 consecutive patients undergoing HIFU (71) or TCAP (56) in our departments were assessed prospectively. Blood samples were collected 24 h before (T0), during surgery (T1), at the end of anaesthesia (T2), and at 12 (T3), 24 (T4) and 36 h after surgery (T5). The extent of the systemic response to surgery-induced tissue trauma was measured by assessing the levels of acute-phase markers tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, C-reactive protein (CRP) and serum amyloid A (SAA), at all sampling times in all patients. RESULTS: The median (interquartile range) age in the HIFU and TCAP groups was 70 (62-77) and 68 (59-75) years, respectively (P = 0.4). Baseline levels (T0) of TNF-alpha, IL-6, IL-10, CRP and SAA were comparable in both groups. The levels of all four markers increased during both procedures; the median values were higher for TCAP at T2 (P = 0.02, 0.001, <0.001 and 0.06), T3 (P < 0.001, 0.009, 0.003 and 0.001), T4 (P = 0.007, <0.001, 0.005 and <0.001) and T5 (P < 0.001, 0.004, <0.001 and 0.02), respectively. IL-6 was also higher for TCAP at T1 (P = 0.03). IL-10 did not change at the different sampling times. CONCLUSION: The tissue trauma and associated invasiveness of HIFU is less than that of TCAP, based on the variables objectively measured in this study.

Urinary fibronectin as a predictor of a residual tumour load after transurethral resection of bladder transitional cell carcinoma.

OBJECTIVE: To determine whether the level of urinary fibronectin predicts the residual tumour load after transurethral resection (TUR) of bladder transitional cell carcinoma (TCC). PATIENTS AND METHODS: Urine samples were collected from 167 consecutive patients with suspected bladder cancer admitted for TUR. Samples were taken both before and after surgery. Bladder tumour fibronectin (BTF) was analysed using a solid-phase chemiluminescent immunometric test. Creatinine in urine was also determined and the BTF/creatinine ratio calculated. RESULTS: Patients were divided into a control group of 41 whose previous diagnosis was negative for BT and another of 126 with a positive diagnosis for BT, which was further subdivided into those with and without residual tumour, according to findings from specimens obtained during the second procedure (repeat TUR or cystectomy). After the second procedure, 68 patients (56%) had no residual tumour, whereas 54 (44%) did. Four patients with BT who did not have the second procedure were excluded from the study. The median BTF and BTF/creatinine value in the control group was 33.2 microg/L and 51.4 microg/g, respectively, before the first TUR, and 29.6 microg/L and 46.7 microg/g, respectively, after the first TUR. There were no statistically significant changes in BTF and BTF/creatinine ratio (P = 0.61 and 0.79, respectively). In the group with TCC, the BTF decreased from 211.9 to 97.3 microg/L (P = 0.02) and the BTF/creatinine ratio from 281.6 to 146.5 microg/g (P = 0.009) for those with residual tumour, while it decreased from 195.1 to 34.0 microg/L (P = 0.007) and the BTF/creatinine ratio decreased from 249.1 to 53.7 microg/g (P = 0.003) for those with no residual tumour. After initial TUR, the patients with residual tumour had significantly greater levels of BTF and BTF/creatinine than did those with no residual tumour (P = 0.004 and 0.006, respectively). The receiver operating characteristic curves showed an optimum threshold of 67.8 microg/L and 81.3 microg/g for BTF and the BTF/creatinine in detecting residual tumour, respectively, with a sensitivity of 91.4% and 89.0%, respectively, and a specificity of 87.8% and 85.6%, respectively. CONCLUSION: Urinary fibronectin, in addition to being one of the best markers for diagnosing bladder carcinoma, can be used to determine the presence of residual tumour load after TUR of bladder TCC.

[Transrectal high-intensity focused ultrasound with the Sonablate 500 for the treatment of prostate cancer].

OBJECTIVE: To evaluate the clinical effect of transrectal high-intensity focused ultrasound (HIFU) in the treatment of prostate cancer (PCa). METHODS: A total of 57 PCa patients, 27 localized and 30 advanced, underwent transrectal HIFU with the Sonab- late 500, the localized group treated by transrectal HIFU only, while the advanced group by transrectal HIFU combined with androgen ablation. RESULTS: For the HIFU treatment, the mean operating time, hospital stay and follow-up were 111 mm (ranging from 86 to 153 mm), 3.2 days (ranging from 2 to 18 days) and 18 months (ranging from 6 to 30 months), respectively. The biochemical disease-free rates at 1, 2 and 3 years in the localized group were 86%, 81% and 79%, respectively. While in the advanced group, the serum prostate specific antigen (PSA) was < 4.0 microg/L in 26 cases ( < 0.51 microg/L in 20) and the prostate volume decreased more than 50% in 21 cases after treated for an average of 8 months (ranging from 3 to 24 months). After transrectal HIFU prostate ablation, the prostate volume reduced, serum PSA lowered, Qmax raised and IPSS improved significantly (P < 0.05). No serious complications occurred including severe urethrorectal fistula and incontinence. CONCLUSION: Transrectal HIFU is a safe, effective and minimally invasive therapy for patients with prostate cancer.