Statistical optimization of culture medium for production of exopolysaccharide from endophytic fungus Bionectria ochroleuca and its antitumor effect in vitro

Endophytic fungi have been recognized as possible useful sources of bioactive metabolites. However, exopolysaccharide (EPS) production from endophytic fungi and its antitumor activity have been less explored. In the present study, endophtic fungus Bionectria ochroleuca M21 was exploited for the production of EPS in submerged culture. Among tested medium components, glucose, yeast extract, MgSO4 and Tween80 were found to be effective and significant on EPS production. Response surface methodology (RSM) was employed to optimize medium composition. The results showed that the significant factors were glucose, yeast extract and Tween80. The optimal medium was observed at the composition of glucose 55.7 g/L, yeast extract 6.04 g/L, MgSO4 0.25g/L and Tween80 0.1 % (v/v). Using the optimized medium, EPS production was achieve at 2.65 ± 0.16 g/L after 4 days fermentation in a 5L bioreactor. Examination of cytotoxicity showed that the EPS from B. ochroleuca M21 did not have cytotoxic activity on human liver HL-7702 cells at concentration 0.025–1.6 mg/mL. In contrast, the EPS exhibited antiproliferative activities against cell lines of liver cancer (HepG2), gastric cancer (SGC-7901) and colon cancer (HT29) in a dose- and time-dependent manner in the concentration ranges of 0.1-0.45 mg/mL

Clinical analysis of rituximab for adult refractory primary membranous nephropathy

Objective·To evaluate clinical efficacy and safety of rituximab (RTX) in the patients with refractory primary membranous nephropathy (PMN).Methods·A retrospective analysis was carried out on the patients with refractory PMN, who had recurred or had not achieved clinical remission after more than 1 year of treatment with glucocorticoid and cyclosporine, cyclophosphamide or tacrolimus, admitted to the Department of Nephrology, Qingpu Branch of Zhongshan Hospital, Fudan University from July 2018 to April 2022. They received 2 doses of RTX. The single dose of RTX was 1 000 mg, and the interval between the two doses was 2 weeks. After 6 months, the numbers of peripheral blood B cells of the patients were detected. If the count of peripheral blood B cells were greater than 5 cell/µL, another 1 000 mg RTX would be added. The main indicators were serum albumin, serum creatinine, urinary protein/creatinine ratio (UPCR), blood antibody against phospholipase A2 receptor (PLA2R) antibody, peripheral blood B cell count, and serum total IgG level. The clinical efficacy and safety of the treatment regimen were evaluated by observing the change of the main indicators of patients and adverse reactions.Results·A total of 18 patients were included, with an average age of (58.17±16.73) years, including 11 males. The total dose of RTX was (2 222.22±485.07) mg, and the follow-up time after RTX treatment was (14.9±4.9) months. At the last follow-up, the serum albumin level was significantly higher than that before RTX treatment [(36.50±5.33) g/L vs (27.61±8.59) g/L, P=0.009]; the serum creatinine level was stable (P>0.05); the value of UPCR decreased significantly [863.30 (203.20, 2 291.75) mg/g vs 2 954.00 (1 458.00, 7 260.75) mg/g, P=0.047]; the PLA2R antibody decreased significantly [(44.32±33.71) RU/mL vs (168.40±88.40) RU/mL, P=0.015]; the peripheral blood B cell count decreased significantly [(37.89±12.43) cell/µL vs (246.40±239.98) cell/µL, P=0.009]; the total blood IgG level was stable (P>0.05). After RTX treatment, 8 patients achieved complete remission (44.4%), 7 patients achieved partial remission (38.9%), and the overall effective rate was 83.3%; only 3 patients were unrelieved (16.7%). In terms of adverse reactions, 1 patient had transfusion allergy reaction, and 1 patient had pulmonary infection.Conclusion·For the patients with refractory PMN who have relapse or do not relieve after traditional immunosuppressive therapy, RTX treatment can effectively induce clinically complete remission or partial remission with good safety

Optoelectronic properties of atomically thin ReSSe with weak interlayer coupling

Rhenium dichalcogenides, such as ReS2 and ReSe2, have attracted a lot of interests due to the weak interlayered coupling in these materials. Studies of rhenium based dichalcogenide alloys will help us understand the differences between binary rhenium dichalcogenides. They will also extend the applications of two-dimensional (2D) materials through alloying. In this work, we studied the optoelectronic properties of ReSSe with a S and Se ratio of 1 : 1. The band gap of the ReSSe alloy is investigated by optical absorption spectra as well as theoretical calculations. The alloy shows weak interlayered coupling, as evidenced by the Raman spectrum. A field-effect transistor based on ReSSe shows typical n-type behavior with a mobility of about 3 cm2 V-1 s-1 and an on/off ratio of 105, together with the in-plane anisotropic conductivity. The device also shows good photoresponse properties, with a photoresponsivity of 8 A W-1. The results demonstrated here will provide new avenues for the study of 2D materials with weak interlayer interactions and in-plane anisotropy

Systematic identification and characterization of chicken (Gallus gallus) ncRNAs

Recent studies have demonstrated that non-coding RNAs (ncRNAs) play important roles during development and evolution. Chicken, the first genome-sequenced non-mammalian amniote, possesses unique features for developmental and evolutionary studies. However, apart from microRNAs, information on chicken ncRNAs has mainly been obtained from computational predictions without experimental validation. In the present study, we performed a systematic identification of intermediate size ncRNAs (50–500 nt) by ncRNA library construction and identified 125 chicken ncRNAs. Importantly, through the bioinformatics and expression analysis, we found the chicken ncRNAs has several novel features: (i) comparative genomic analysis against 18 sequenced vertebrate genomes revealed that the majority of the newly identified ncRNA candidates is not conserved and most are potentially bird/chicken specific, suggesting that ncRNAs play roles in lineage/species specification during evolution. (ii) The expression pattern analysis of intronic snoRNAs and their host genes suggested the coordinated expression between snoRNAs and their host genes. (iii) Several spatio-temporal specific expression patterns suggest involvement of ncRNAs in tissue development. Together, these findings provide new clues for future functional study of ncRNAs during development and evolution

Optimization of 4-( N -Cycloamino)phenylquinazolines as a Novel Class of Tubulin-Polymerization Inhibitors Targeting the Colchicine Site

The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a–c and 5a–m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI50 1.9–3.2 nM), significant potency against tubulin assembly (IC50 0.77 μM), and substantial inhibition of colchicine binding (99% at 5 μM). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose

Effect of EVA and DCP addition on injection moldability and tensile properties of recycled PE from disposable drip tapes

The effects of ethylene-vinyl acetate copolymer (EVA) and dicumyl peroxide (DCP) addition on injection moldability and tensile properties of recycled polyethylene (PE) from disposable drip tapes were studied. DCP showed an adverse impact on the injection moldability of recycled PE materials, while EVA had positive effects on it. Tensile properties of the reproduced PE increased with the increasing amount of EVA up to 10 wt.% and decreased beyond it. The DCP addition reduced the elastic properties of the reproduced PE, while it enhanced the tensile strength. Overall, the co-addition of 6 wt.% EVA + 0.4 wt.% DCP could improve the tensile strength of the reproduced PE materials

NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury

Abstract The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia–reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia–reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases. Graphical Abstrac

CircRNA Expression Profiles in Canine Mammary Tumours

Numerous studies have shown that the occurrence and development of tumours are associated with the expression of circular RNAs (circRNAs). However, the expression profile and clinical significance of circRNAs in canine mammary tumours remain unclear. In this paper, we collected tissue samples from three dogs with canine mammary tumours and analysed the expression profiles of circRNAs in these samples using high-throughput sequencing technology. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses revealed 14 biological processes associated with these genes, and 11 of these genes were selected for qRT-PCR to verify their authenticity. CircRNAs have sponge adsorption to miRNAs, so we constructed a circRNA-miRNA network map using Cytoscape software. As a result, we identified a total of 14,851 circRNAs in canine mammary tumours and its adjacent normal tissues. Of these, 106 were differentially expressed (fold change ≥ 2, p ≤ 0.05), and 64 were upregulated and 42 were downregulated. The GO analysis revealed that the biological processes involved were mainly in the regulation of the secretory pathway, the regulation of neurotransmitter secretion and the positive regulation of phagocytosis. Most of these biological pathways were associated with the cGMP-PKG (cyclic guanosine monophosphate) signalling pathway, the cAMP (cyclic adenosine monophosphate) signalling pathway and the oxytocin signalling pathway. After screening, source genes closely associated with canine mammary tumours were found to include RYR2, PDE4D, ROCK2, CREB3L2 and UBA3, and associated circRNAs included chr27:26618544-26687235-, chr26:8194880-8201833+ and chr17:7960861-7967766-. In conclusion, we reveals the expression profile of circRNAs in canine mammary tumours. In addition, some circRNAs might be used as potential biomarkers for molecular diagnosis