Research progress of immunotherapy for advanced head and neck cancer.

Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted. This review summarizes the mechanism, clinical application and safety of immunotherapy for advanced head and neck cancer.

Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation.

Circular RNAs (circRNAs) can regulate the progression of neuroblastoma (NB) via miRNA/mRNA axis. This study aimed to investigate the functional mechanism of hsa_circ_0001361 in NB. Hsa_circ_0001361, miR-490-5p and tripartite motif 2 (TRIM2) were detected through reverse transcription-quantitative polymerase chain reaction. The proliferation ability was examined using cell counting kit-8 assay, colony formation assay and ethynyl-2'-deoxyuridine assay. Cell migration and invasion were assessed via transwell assay and wound healing assay. The protein levels were measured by western blot. Glycolysis was analyzed via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed for target analysis. Hsa_circ_0001361 research in vivo was performed using xenograft tumor assay. Hsa_circ_0001361 was overexpressed in NB tissues and cells. Hsa_circ_0001361 downregulation suppressed cell proliferation, metastasis and glycolysis. Hsa_circ_0001361 served as a miR-490-5p sponge. The functions of hsa_circ_0001361 in NB cells were associated with miR-490-5p sponging effect. Hsa_circ_0001361 resulted in TRIM2 expression change via targeting miR-490-5p. MiR-490-5p acted as a tumor inhibitor in NB by downregulating TRIM2. Hsa_circ_0001361 knockdown reduced tumor growth in vivo through mediating miR-490-5p/TRIM2 axis. Our results suggested that hsa_circ_0001361 upregulated TRIM2 by absorbing miR-490-5p, thereby promoting cell malignant behaviors and glycolytic metabolism in NB.

Increasing production and bio-accessibility of natural astaxanthin in Haematococcus pluvialis by screening and culturing red motile cells under high light condition.

The thick cell wall and low astaxanthin productivity were two important bottlenecks limiting industrial production of astaxanthin via Haematococcus pluvialis. This study reports a strategy for increasing production and bio-accessibility of astaxanthin in H. pluvialis by screening and culturing red motile cells under high light condition. Compared with the original strain NBU489, the biomass of the novel isolated strain RMS10 increased by 31.9% under low light condition, and the astaxanthin content (44.6 mg/g) increased by 53.3% after 9-day high light induction, which were readily extracted and digested without cell disruption. Subsequent transcriptomic analysis confirmed the accumulation of astaxanthin and lipids in RMS10 cells as expression of genes associated with biosynthesis of fatty acid and astaxanthin were up-regulated, while those involved in thick cell wall biosynthesis and reactive oxygen species scavenging were down-regulated in RMS10. Collectively, this study provides a simple and effective method for economical production of natural astaxanthin.

Buffering culture solution significantly improves astaxanthin production efficiency of mixotrophic Haematococcus pluvialis.

Sodium acetate (NaAc) supplementation, often used to increase the growth of H. pluvialis under low light, but promotes cell death under high light; its underlying reasons and solutions are rarely reported. Here, NaAc supplementation was found to rapidly increase pondus hydrogenii (pH) of culture solution, elevate reactive oxygen species (ROS), and cause cell death immediately under higher light. Adjusting pH of NaAc supplemented culture solution with 10 mM Tris-HCl once before high light significantly reduced cell mortality and increased astaxanthin yield. When verified in a 5-litre photobioreactor, this novel method produced over 4.0% of dry weight (DW) astaxanthin within only 8-10 days. In summary, this study explained reasons underlying NaAc supplementation-induced cell death and provided an rapid, easy and effective method to produce high amount of astaxanthin in H. pluvialis.

Exposure to MPA-capped CdTe quantum dots causes reproductive toxicity effects by affecting oogenesis in nematode Caenorhabditis elegans.

Quantum dots (QDs), considered as a type of excellent semiconductor nanomaterial, are widely employed and have a number of important applications. However, QDs have the potential to produce adverse effects and toxicity with the underlying molecular mechanisms not well understood. Herein, Caenorhabditis elegans was used for in vivo toxicity assessment to detect the reproductive toxicity of CdTe QDs. We found that exposure to CdTe QDs particles (≥ 50 mg/L) resulted in a defect in reproductive capacity, dysfunctional proliferation and differentiation, as well as an imbalance in oogenesis by reducing the number of cells in pachytene and diakinesis. Further, we identified a SPO-11 and PCH-2 mediated toxic mechanism and a GLP-1/Notch mediated protective mechanism in response to CdTe QDs particles (≥ 50 mg/L). Taken together, these results demonstrate the potential adverse impact of CdTe QDs (≥ 50 mg/L) exposure on oogenesis and provide valuable data and guidelines for evaluation of QD biocompatibility.

Cobalt/Copper-Cocatalyzed Synthesis of Imidazo[1,2-a:3,4-a']dipyridiniums from 2H-[1,2'-Bipyridin]-2-ones and 2-Bromoacetophenones.

A cobalt/copper-cocatalyzed facile synthesis of imidazo[1,2-a:3,4-a']dipyridiniums from 2H-[1,2'-bipyridin]-2-ones and 2-bromoacetophenones is presented. This strategy provides an alternative to the imidazo[1,2-a:3,4-a']dipyridinium synthesis by employing readily available substrates and a simple procedure, which would render this method potentially useful in organic synthesis.

Cp*CoIII-Catalyzed Synthesis of Pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums via Tandem C-H Activation and Subsequent Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes.

A Cp*CoIII-catalyzed C2-selective C-H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2',1':2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-ium by NaBH4.

The Use of the Nematode Caenorhabditis elegans to Evaluate the Adverse Effects of Epoxiconazole Exposure on Spermatogenesis.

There is increasing evidence that epoxiconazole exposure can affect reproductive function, but few studies have investigated adverse effects on spermatogenesis. The nematode Caenorhabditis elegans (C. elegans) was used in our study to assess effects of epoxiconazole on spermatogenesis in male nematodes after 48 h of exposure to concentrations of 0.1, 1.0, or 10.0 µg/L. The results demonstrated that epoxiconazole exposure affected spermatogenesis, decreasing the number of total germ cells, mitotic cells, meiotic cells and spermatids, spermatid diameter, and cross-sectional area, and inducing mitotic germ cell proliferation arrest, premature entry into meiosis, and sperm activation inhibition; however, sperm transfer showed no abnormal changes. In addition, the results showed that epoxiconazole activated the transforming growth factor-ß (TGFß) signaling pathway and increased the expression levels of gene daf-1, daf-3, daf-4, daf-5 and daf-7 in nematodes. We therefore propose that epoxiconazole acts by activating the TGFß signaling pathway, leading to the impairment of spermatogenesis and the consequent decline in male fertility.