Morphology and multi-gene phylogeny reveal a novel Torula (Pleosporales, Torulaceae) species from the plateau lakes in Yunnan, China.

Background: During an investigation into lignicolous freshwater fungi from the plateau lakes in Yunnan Province, China, two fresh collections of Torula taxa were collected and examined morpholgically. New information: Torulaluguhuensis is characterised by: conidiophores which are semi-macronematous mononematous, erect, septate, smooth, slightly flexuous and pale brown; conidiogenous cells which are holoblastic, mono- to polyblastic, integrated, terminal, terminal or intercalary in conidial chains, doliiform and pale brown; conidia which are branched chains, acrogenous, straight or slightly curved, dark brown to blackish, pale brown or subhyaline at apex, 1-3 septate, strongly constricted at the septa, verruculose or finely echinulate and rounded at both ends. A new species was introduced, based on morphological and phylogenetic analysis of combined ITS, LSU, RPB2 and TEF sequence data. Detailed descriptions and illustrations are provided, with an updated phylogenetic tree depicting intergeneric relationships within the Torulaceae.

Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.

Preliminary evaluation of a small interfering RNA molecular probe targeting murine double minute 2 in breast cancer.

INTRODUCTION: Murine double minute 2 (MDM2) is an oncogene that is important in tumorigenesis, tumor metastasis and chemotherapy resistance. We aimed to synthesize a molecular imaging probe, 99m Tc-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [ 99m Tc]HYNIC-siRNA 1489 molecular probe provided an effective way of assessing MDM2 expression via single-photon emission computed tomography. METHOD: Three siRNAs were designed, and their inhibitory efficiencies were determined using western blots and qRT-PCR. The selected siRNA was labeled with the radionuclide technetium-99m ( 99m Tc) through the chelator HYNIC. The bioactivity and properties of [ 99m Tc]HYNIC-siRNA 1489 were evaluated prior to imaging in mice. Imaging and biodistribution of the probe were used to assess its targeting ability. RESULTS: SiRNA 1489, which was labeled with 99m Tc, displayed a strong inhibitory effect in Michigan Cancer Foundation-7 cell lines. The radiochemical purity of [ 99m Tc]HYNIC-siRNA 1489 was stable at various temperatures in phosphate-buffered serum and bovine serum. The tumor/muscle ratio in mice injected with [ 99m Tc]HYNIC-siRNA 1489 was higher than that in those injected with the negative control, [ 99m Tc]HYNIC-NC siRNA. The percentage injected dose per gram (%ID/g) of the tumors injected with 99m Tc-HYNIC-siRNA 1489 was greater than that of the control group. CONCLUSION: The [ 99m Tc]HYNIC-siRNA 1489 was taken up by the tumor, which had a high level of MDM2. The probe exhibited a sufficient retention time in the tumor. This probe may be an effective strategy for evaluating MDM2 expression and achieving early diagnosis in breast cancer.

Molecular imaging and treatment of PSMA-positive prostate cancer with 99mTc radiolabeled aptamer-siRNA chimeras.

INTRODUCTION: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PCa). The aptamer (Apt) A10-3.2 can be used as a specific ligand for the early diagnosis and targeted treatment of PCa. siRNA-Apt has been used to therapeutically target PSMA-positive PCa. We aimed to synthesize a new type of molecular probe to facilitate the integration of diagnosis and treatment for PSMA-positive PCa. METHODS: Chimeras were obtained by covalent linking PSMA Apt-A10-3.2 and the MDM2 siRNA. SHNH, a bifunctional chelating agent, was used to couple 99mTc with chimeras to synthesize a new molecular probe. Labeling efficiency, radiochemical purity, and stability were confirmed using a γ-well counter and Whatman paper No.1. SPECT imaging and biodistribution studies were performed on BALB/c mice bearing 22Rv1 or PC-3 xenografts. Tumor inhibition and cytotoxicity of Chimeras were evaluated. LNCaP, 22RV1, and PC-3 PCa cell lines were used for in vitro and in vivo experiments. RESULTS: [99mTc]Tc-chimeras showed high labeling efficiency (61.47% ± 2.85%, n = 3), radiochemical purity (>95%), and stability. Biodistribution studies and SPECT imaging with 99mTc-chimeras in mice bearing 22Rv1 xenografts demonstrated a high T/M ratio (4.63 ± 0.68, n = 3) and a high T/B ratio (3.61 ± 0.7, n = 3) at 2 h post-injection. 99mTc-chimeras showed rapid renal clearance. Compared with the PBS group, tumor growth in the chimera group was significantly inhibited (P < 0.01, n = 4), but there was no significant difference in body weight (p > 0.05, n = 4). H&E staining showed no obvious liver or kidney damage. CONCLUSIONS: Our study proved that [99mTc]Tc-Aptamer-siRNA chimeras could be used to diagnose and treat PSMA-positive PCa in vivo.

Noninvasive evaluation of HABP1 expression with 99mTc-labeled small-interference RNA in ovarian cancer.

PURPOSE: Ovarian cancer is one of the most common gynecological cancers in women with a low 5-year survival rate. Evaluation of hyaluronic acid-binding protein 1 (HABP1) level can provide important information for the diagnosis and treatment of ovarian cancer. In this study, we designed a novel HABP1 probe based on 99mTc-radiolabeled small-interference RNA (siRNA) for detecting HABP1 expression noninvasively in vivo, thereby providing a new method for its diagnosis and treatment. METHODS: A specific siHABP1 was selected because of its targetability and silencing effect. A negative control siRNA (NCsiRNA) with no homology with the human genome was used. SiHABP1 and NCsiRNA were radiolabeled with 99mTc using the bifunctional chelating agent hydrazinonicotinamide (HYNIC). The radiochemical purity and in vitro stability of the probe were determined by HPLC. The binding activity was measured by western blotting (WB) and RT-PCR. The HABP1-overexpressing human ovarian cancer cell line HO-8910 was used for cell uptake experiments, which were performed with or without transfection and measured with a gamma counter. HO8910-bearing mice were imaged at 1, 4, and 10 h, and biodistribution analysis was performed at 1, 4, 6, and 10 h after injection of 99mTc-HYNIC-siRNA. RESULTS: 99mTc-HYNIC-siHABP1 had high radiochemical purity and good in vitro stability, and showed the same binding capacity and silencing effect as siHABP1. SPECT imaging showed that tumors were clearly visualized at 10 h after injection of 99mTc-HYNIC-siHABP1 but not after 99mTc-HYNIC-NCsiRNA, implying specific binding. The biodistribution results were consistent with those of SPECT imaging. CONCLUSIONS: We showed that 99mTc-HYNIC-siHABP1 is a feasible probe for the noninvasive visualization of HABP1 expression in ovarian cancer.

Circular RNA circ-NCOR2 accelerates papillary thyroid cancer progression by sponging miR-516a-5p to upregulate metastasis-associated protein 2 expression.

OBJECTIVE: Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and the fifth most common cancer in women. Circular RNAs (circRNAs) have been shown to play vital functions in cancers, but few studies have focused on the functions and mechanism of dysregulated circRNAs in PTC. METHODS: Quantitative reverse transcription PCR was used to measure circ-NCOR2 levels in PTC tissues and cell lines. The functions of circ-NCOR2 in PTC were examined by analysis using the cell counting kit-8, clone forming, flow cytometry, and Transwell experiments. Bioinformatic analysis and dual luciferase reporter gene testing were used to identify the mechanisms of circ-NCOR2. RESULTS: Circ-NCOR2 overexpression was observed in PTC tissues and cells. Silenced or overexpressed expression of circ-NCOR2 strikingly attenuated or facilitated, respectively, the growth, migration, and invasion of PTC cells. Mechanistically, miR-615a-5p was identified as the target of circ-NCOR2. Moreover, circ-NCOR2 enhanced the expression of metastasis-associated protein 2 (MTA2) by sponging miR-615a-5p, thereby facilitating PTC cell progression. CONCLUSIONS: Taken together, our findings reveal a novel circ-NCOR2/miR-615a-5p/MTA2 axis in PTC, which could become a potential therapeutic target for this disease.

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism.

The current study observed the percentage of peripheral blood (PB) CD4+CD25+ regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the proliferation of naïve CD4 T cells in patients with hyperthyroidism. Furthermore, preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs on hyperthyroidism attacks. The present study identified that compared with the percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs exhibited significantly reduced inhibition of the proliferation of naïve CD4 T cells and decreased secretion capacity on the cytokines of CD4 T cells, compared with those of healthy control subjects (P<0.05). In addition, it was demonstrated that thyroid function of patients with hyperthyroidism was significantly improved (P<0.05) subsequent to receiving medication. Compared with the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism patients following treatment (P>0.05). In the patients with hyperthyroidism, following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition of the proliferation of naïve CD4 T cells and increased secretion capacity of CD4 T cell cytokines, compared with those of the patients with hyperthyroidism prior to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with hyperthyroidism, and its non­proportional decrease may be closely associated with the occurrence and progression of hyperthyroidism.

Effects of dietary fresh fermented soybean meal on growth performance, ammonia and particulate matter emissions, and nitrogen excretion in nursery piglets.

This study was conducted to investigate the effects of fresh fermented soybean meal (FSM) on the growth performance of nursery piglets, nitrogen excretion in feces, and the concentrations of ammonia (NH3) and particulate matter (PM) in the piggery. A total of 472 nursery piglets (Landrace×Yorkshire, (16.3±0.36) kg body weight) were randomly allocated into two treatments with 236 pigs in each treatment. The pigs were fed the basal diet without fresh FSM (control) or diet containing 10% (100 g/kg) fresh FSM (FSM group), and the crude protein content of the two groups was consistent. The feeding trial lasted for 28 d. The results showed that the pigs fed fresh FSM had increased (P<0.05) average daily gain (ADG) compared with the control. There was no significant difference (P>0.05) in feed to gain ratio (F:G) between the two groups. During the whole experiment, the concentration of NH3 in the piggery decreased (P<0.05) by 19.0%, and the concentrations of PM (PM10 and PM2.5) in the piggery decreased (P<0.05) by 19.9% and 11.6%, respectively, in the FSM group, compared with the control. The ammonia nitrogen and nitrite content in feces increased (P<0.05) by 32.9% and 28.4%, respectively, in the FSM group. The fecal pH declined (P<0.05) significantly in the FSM group compared with the control. At the end of experiment, total protein (TP) concentration was increased (P<0.05) significantly and blood urea nitrogen (BUN) concentration was decreased (P<0.05) for pigs fed the diet with fresh FSM. The results indicated that dietary fresh FSM not only improved the growth performance of nursery piglets, but also reduced the NH3 concentration in the piggery due to nitrogen conversion, and decreased the concentrations of PM10 and PM2.5 in the piggery.

Treatment of Graves' ophthalmopathy with an in-house Phosphorus-32 source: Initial clinical observations.

The objective of the present study was to observe the therapeutic effect of radiation delivered via a 32P source on Graves' ophthalmopathy. A32P solution was injected into a 10-ml vacuum flask held inside a lead container. A window was cut in the lead, generating a treatment beam. Radiation was given to four areas: The upper and lower orbit (covering ~1/3 of the eyelid) and the inner and outer canthus. Each site received 10 daily doses of 20 cGy. Proptosis was measured by an exophthalmometer and the palpebral aperture was determined with a ruler. Measurements were taken before and after the treatment. After 5 days of treatment, the patient displayed a significant improvement, and by 10 days, the average reduction of proptosis in Graves' ophthalmopathy was 3.36±1.73 mm for the left and 3.05±2.04 mm for the right eyes. The treatment was effective in all patients, who uniformly reported rapid pain relief. Conjunctival congestion and eyelid edema also improved significantly. However, only 50% of patients showed improved diplopia after treatment, which was poor compared with other symptoms. No obvious side effects were found in the subsequent follow-up. In conclusion, 32P brachytherapy for Graves' ophthalmopathy was simple and effective, with few side effects, and should be considered as a promising therapy.

WITHDRAWN: Correlations of CTLA-4 exon-1 rs231775A>G and promoter region rs5742909C>T polymorphisms with the therapeutic efficacy of 131I radionuclide in Graves' disease.

The Accepted Manuscript version of this article (published on 6 June 2017) was withdrawn on 16 November 2017 at the request of the authors.