Hybridization chain reaction cascaded amplification platform for sensitive detection of pathogen.

Rapid, sensitive, and accurate identification of pathogens is vital for preventing and controlling fish disease, reducing economic losses in aquaculture, and interrupting the spread of food-borne diseases in human populations. Herein, we proposed a hybridization chain reaction (HCR) cascaded dual-signal amplification platform for the ultrasensitive and specific detection of pathogenic microorganisms. A couple of specific primers for target bacterial 16S rRNAs were used to obtain amplified target single-stranded DNAs (AT-ssDNA). Then, AT-ssDNA initiated HCR amplification along with the opening of fluorophore (FAM) and a quencher (BHQ1) labeled hairpin reporter probe (H1), and the FAM fluorescence signal recovered. The proposed strategy could achieve a detection limit down to 0.31 CFU/mL for Staphylococcus aureus (S. aureus), 0.49 CFU/mL for Escherichia coli (E. coli) in buffer, and a linear range from 1 to 1 × 106 CFU/mL for S. aureus, 1 to 1 × 107 CFU/mL for E. coli. Furthermore, this platform enabled sensitive and precise detection of pathogenic microorganisms in complex samples such as fish blood and different organ tissues (large intestine, gallbladder, heart, liver, ren, gill, skin), which shows great potential in disease prevention and control in aquatic products.

Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1.

Chemical investigation of the fermentation extract of the coral-associated fungus Aspergillus sp. ITBBc1 led to the discovery of five unreported p-terphenyl derivatives, sanshamycins A-E (1-5), together with five previously described analogues, terphenyllin (6), 3-hydroxyterphenyllin (7), candidusin A (8), 4,5-dimethoxycandidusin A (9), and candidusin C (10). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound 1 represents the first example of p-terphenyls with an aldehyde substitution on the benzene ring. Compounds 2-4 feature varying methoxyl and isopentenyl substitutions, while compound 5 features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of p-terphenyl natural products. Compounds 1-6 and 9 were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound 3 was the most potent and exhibited PDE4D inhibitory activity with an IC50 value of 5.543 µM.

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI.

BACKGROUND: Osteosarcoma (OS) is an aggressive bone cancer that most commonly affects adolescents and children. Emerging studies have shown that long noncoding RNA (lncRNA) performs essential roles in the occurrence and development of many tumors. Prostate androgen-regulated transcript 1 (PART 1) has been reported as a tumor oncogene; despite this, the mechanisms underlying its involvement in OS are unclear. METHODS: OS and paired normal tissue samples were obtained, and gene expressions were detected by real time-quantitative polymerase chain reaction (RT-qPCR). The functions of PART 1 in OS cell proliferation, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8) and Transwell assays. Furthermore, the binding sites of PART 1 and miR-20b-5p as well as those between miR-20b-5p and bone morphogenic protein and activin membrane-bound inhibitor homolog (BAMBI) were verified by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: Our study found obvious overexpression of PART 1 in OS tissues and cells. Furthermore, PART 1 overexpression facilitated OS cell proliferation, invasion, and migration. Further mechanistic investigations revealed that PART 1 could sponge to miR-20b-5p, which was expressed at a low level in OS tissues and cells. Importantly, miR-20b-5p overexpression inhibited OS cell proliferation, invasion, and migration. Additionally, BAMBI was confirmed as a downstream gene of miR-20b-5p, and its expression was reversely modulated by miR-20b-5p and positively modulated by PART 1. Rescue experiments suggested that BAMBI was involved in PART 1-mediated promotion of OS progression. CONCLUSIONS: PART 1 serves as a competing endogenous RNA to promote OS tumorigenesis via its regulation of the miR-20b-5p/BAMBI axis, which may provide a promising therapeutic biomarkers for OS patients.

A new flavonoid derivative and a new 5-hydroxyanthranilic acid derivative from the sea urchin-derived Streptomyces sp. HDa1.

One new flavonoid derivative flavoside A (1), one new 5-hydroxyanthranilic acid derivative crassilin (2), along with the known angucyclinone PD116740 (3) and oxachelin (4), was isolated from the EtOAc extract of the fermentation broth of the sea urchin (Anthocidaris crassispina)-derived actinobacterium, Streptomyces sp. HD01. The structures of these compounds were established on the basis of their HR-ESI-MS and NMR spectroscopic data. All of these compounds were assessed for their antibacterial activity.

Anthocidins A⁻D, New 5-Hydroxyanthranilic Acid Related Metabolites from the Sea Urchin-Associated Actinobacterium, Streptomyces sp. HDa1.

Four new 5-hydroxyanthranilic acid related compounds, named anthocidins A⁻D (1⁻4), two known analogues n-lauryl 5-hydroxyanthranilate (5) and isolauryl 5-hydroxyanthranilate (6), together with benzamide (7), 3-hydroxy-4-methoxycinnamamide (8), and (3S-cis)-hexahydro-3-[(3,4-dihydroxyphenyl)methyl]pyrrolo[1,2-a]pyrazine-1,4-dione (9), were isolated from the fermentation broth of the marine-derived actinomycete, Streptomyces sp. HDa1, which was isolated from the gut of a sea urchin, Anthocidaris crassispina, collected from Hainan Island, China. The structures of these secondary metabolites were elucidated on the basis of their 1D and 2D-NMR and mass spectroscopic data, and anthocidin A was confirmed by single-crystal X-ray diffraction with Cu Kα radiation. Anthocidins A⁻D (1⁻4) feature an acetyl group substitution at the amino group and varying alkyl side chains at the carboxyl group of 5-hydroxyanthranilic acid, and compound 5 was isolated as a natural product for the first time. The cytotoxic and antibacterial activity of compounds 1⁻9 were evaluated.

Long noncoding RNA PCAT-1 acts as an oncogene in osteosarcoma by reducing p21 levels.

Long non-coding RNA (lncRNA) is emerging as a critical regulator in multiple cancers. Recently, lncRNA PCAT-1 was found to be up-regulated in prostate cancer and hepatocellular carcinoma, exerting oncogenic effects. However, the biological function and regulatory mechanism of PCAT-1 remain unclear in osteosarcoma (OS). In this study, we reported that PCAT-1 expression was also upregulated in OS tissues, and its overexpression was remarkably associated with tumor size, Enneking stage, tumor node metastasis (TNM) stage and metastasis in patients with OS. Knockdown of PCAT-1 suppressed OS cells proliferation, migration and invasion in vitro, and inhibited the tumorigenicity of OS cells in vivo. Mechanistic investigations revealed that PCAT-1 could interact with EZH2, thereby repressing p21 expression. Additionally, rescue experiments indicated that PCAT-1 functioned as an oncogene partly via suppressing p21 in OS cells. Collectively, our findings demonstrate that PCAT-1 is a new candidate for use in OS diagnosis, prognosis and therapy.

Spiculisporic acids B­D, three new γ-butenolide derivatives from a sea urchin-derived fungus Aspergillus sp. HDf2.

Three new γ-butenolide derivatives 1–3, named spiculisporic acids B–D, were isolated from the culture of Aspergillus sp. HDf2, a marine-derived fungus that resides in the sea urchin, Anthocidaris crassispina. The structures of 1–3 were elucidated on the basis of spectroscopic methods, including MS and 2D NMR techniques. Their in vitro cytotoxic activities against two cell lines (SGC-7901, human gastric adenocarcinoma and SPC-A-1, human lung adenocarcinoma) and inhibitory activities against Staphylococcus aureus ATCC 51650 were investigated.