Rapid Discovery of Substances with Anticancer Potential from Marine Fungi Based on a One Strain-Many Compounds Strategy and UPLC-QTOF-MS.

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.

[Contamination and Probabilistic Health Risk Assessment of Heavy Metals in Agricultural Soils Around a Lead-Zinc Smelter].

In order to identify the contamination and health risks of heavy metals in agricultural soils, a total of 56 surface soil samples (0-20 cm) were collected around a Pb-Zn smelter in Yunnan Province, and six heavy metals (Pb, Cd, Zn, As, Cu, and Hg) and pH were analyzed to assess heavy metal status, ecological risk, and probabilistic health risk. The results revealed that the average contents of six heavy metals (Pb:4413.93 mg·kg-1, Cd:6.89 mg·kg-1, Zn:1672.76 mg·kg-1, As:44.45 mg·kg-1, Cu:47.61 mg·kg-1, and Hg:0.21 mg·kg-1) were higher than their background values in Yunnan Province. Cd had the highest mean geo-accumulation index (Igeo) of 0.24, the highest mean pollution index (Pi) of 30.42, and the greatest average ecological risk index (Er) of 1312.60, indicating that Cd was the primary enriched and highest-ecological risk pollutant. The mean hazard index (HI) through exposure to six HMs was 2.42E-01 and 9.36E-01 for adults and children, respectively, with 36.63% of HI values for children exceeding the risk threshold of 1. Moreover, the mean total cancer risks (TCR) were 6.98E-05 and 5.93E-04 for adults and children, respectively, with 86.85% of TCR values for children exceeding the guideline value of 1E-04. The probabilistic health risk assessment suggested that Cd and As were the main contributors for the non-carcinogenic risks and carcinogenic risks. This work will provide scientific reference for the precise risk management and effective remediation strategy of soil heavy metal pollution in this study area.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

A New Technique: Laparoscopic Resection of Fibrous Ring and Placing Extravascular Stent in Patients With Nutcracker Syndrome: A Report of 5 Cases.

OBJECTIVE: To evaluate the feasibility and safety of a new laparoscopic technique for resection of a fibrous ring and extravascular stent implantation in patients with nutcracker syndrome (NCS). MATERIAL AND METHODS: We retrospectively reviewed data of 5 patients diagnosed with NCS between March 2010 and February 2016. The mean age of the patients (4 male and 1 female) was 34 years (range, 28-40 years). All 5 patients underwent laparoscopic resection of the narrow fibrous ring around the left renal venous (LRV) and for extravascular stent implantation in the LRV for management of NCS. RESULTS: The average operating time was104 minutes and the average blood loss during surgery was 59 mL. The average length of the postoperative hospital stay was 6 days (range, 4-8 days). In all 5 patients, the symptoms of macroscopic hematuria started decreasing gradually and resolved after surgery. Postoperative computed tomography showed that the blood outflow from the LRV was smooth. The ratio of the dilated segment's inner diameter to the diameter of the strictured segment decreased from 3.4 to 9.5, preoperatively to 1.1-2.0, postoperatively. The mean follow-up period was 17.6 months (range, 8-24 months).One patient's varicocele was cured and symptoms in all 5 patients resolved after surgery. None of the patients showed symptom recurrence. CONCLUSION: Laparoscopic surgery, for the placement of an extravascular stent and resection of the fibrous ring around the end of the LRV outflow to the inferior vena cava appears feasible and safe and offers an alternative minimally invasive for the management of NCS.

Novel conductive polypyrrole/silk fibroin scaffold for neural tissue repair.

Three dimensional (3D) bioprinting, which involves depositing bioinks (mixed biomaterials) layer by layer to form computer-aided designs, is an ideal method for fabricating complex 3D biological structures. However, it remains challenging to prepare biomaterials with micro-nanostructures that accurately mimic the nanostructural features of natural tissues. A novel nanotechnological tool, electrospinning, permits the processing and modification of proper nanoscale biomaterials to enhance neural cell adhesion, migration, proliferation, differentiation, and subsequent nerve regeneration. The composite scaffold was prepared by combining 3D bioprinting with subsequent electrochemical deposition of polypyrrole and electrospinning of silk fibroin to form a composite polypyrrole/silk fibroin scaffold. Fourier transform infrared spectroscopy was used to analyze scaffold composition. The surface morphology of the scaffold was observed by light microscopy and scanning electron microscopy. A digital multimeter was used to measure the resistivity of prepared scaffolds. Light microscopy was applied to observe the surface morphology of scaffolds immersed in water or Dulbecco's Modified Eagle's Medium at 37°C for 30 days to assess stability. Results showed characteristic peaks of polypyrrole and silk fibroin in the synthesized conductive polypyrrole/silk fibroin scaffold, as well as the structure of the electrospun nanofiber layer on the surface. The electrical conductivity was 1 × 10-5-1 × 10-3 S/cm, while stability was 66.67%. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was employed to measure scaffold cytotoxicity in vitro. Fluorescence microscopy was used to observe EdU-labeled Schwann cells to quantify cell proliferation. Immunohistochemistry was utilized to detect S100ß immunoreactivity, while scanning electron microscopy was applied to observe the morphology of adherent Schwann cells. Results demonstrated that the polypyrrole/silk fibroin scaffold was not cytotoxic and did not affect Schwann cell proliferation. Moreover, filopodia formed on the scaffold and Schwann cells were regularly arranged. Our findings verified that the composite polypyrrole/silk fibroin scaffold has good biocompatibility and may be a suitable material for neural tissue engineering.

[Influence and distribution of CD133 and CD34 antigen expression in proximal tubule epithelial cells during ischemia/reperfusion injury in rats].

OBJECTIVE: To study the influence and distribution in proximal tubule epithelial cells with the expressions of CD133 and CD34 in a rat model so as to provide a study basis for renal adult stem cell. METHODS: The kidney ischemia/reperfusion model was established by blocking the bilateral renal arteries for about 50 min and recovering the renal perfusion of blood. Then the rat kidneys were extracted at Days 3, 5 and 7 post-modeling. After a series of special treatment, immunohistochemical staining was used to show the distribution and expression intensity of KIM-1, Brdu antigen, CD34 and CD133 antigens in cells with the elapsing of time. RESULTS: As compared with control group, the KIM-1 and CD133 antigens were present in cortex renis while the CD34 and Brdu antigens were distributed in parts of medulla renis and juncture of cortex-medulla renis. The expression density value of KIM-1 and CD133 antigens rose for the first 3 days then declined afterward (40.3% ± 3.2%, 57.5% ± 3.8%, 24.3% ± 1.4%). Otherwise the expression density value of CD 34 antigen declined (56.0% ± 4.8%, 44.2% ± 2.2%, 28.8% ± 1.0%) and Brdu antigen showed an upward trend at post-operation (10.0% ± 1.1%, 36.0% ± 4.2%, 48.8% ± 5.0%). CONCLUSION: After ischemia/reperfusion injury in kidney, the expression rates of CD133 and KIM-1 antigen rise obviously in cortex renis. And the D34 and Brdu antigens show a similar trend in medulla renis. The result indicates that the phenomenon of proliferation and differentiation may appears in kidney proximal tubule and migrate from the region of medulla renis to cortex renis. The participating cells not only possess the strong proliferation and repairing ability of stem/progenitor cells, but also can expresses the CD34 and CD133 antigens. Thus it is may provide a study basis for the tissue reconstruction of nephron and research in the field of kidney adult stem cell.