Batf-Dependent Th17 cells act through IL23R pathway to promote prostate adenocarcinoma initiation and progression.

BACKGROUND: The role of Th17 cells in prostate cancer (PCa) is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells. METHODS: In this study, we aimed to characterize the role of Batf-dependent Th17 cells in PCa by crossbreeding Batf knockout (Batf-/-) mice with mice conditionally mutant for Pten. We found that Batf-/- mice had changes in the morphology of prostate epithelial cells compared to normal mice, and Batf-/- mice deficient in Pten (named Batf-) had smaller prostate size and developed fewer invasive prostate adenocarcinomas than Pten-deficient mice with Batf expression (named Batf+). The prostate tumors in Batf- mice showed reduced proliferation, increased apoptosis, decreased angiogenesis and inflammatory cell infiltration, and activation of NF-κB signaling. Moreover, Batf- mice showed significantly reduced IL-23/IL-23R signaling. In the prostate stroma of Batf- mice, IL-23R-positive cells were decreased considerably compared to Batf+ mice. Splenocytes and prostate tissues from Batf- mice cultured under Th17 differentiation conditions expressed reduced IL-23/IL-23R than cultured cells from Batf+ mice. Anti-IL23p19 antibody treatment of Pten-deficient mice reduced prostate tumors and angiogenesis compared to control IgG-treated mice. In human prostate tumors, BATF mRNA level was positively correlated with IL23A and IL-23R but not RORC. CONCLUSION: Our novel findings underscore the crucial role of IL-23/IL23R signaling in mediating the function of Batf-dependent Th17 cells, thereby promoting PCa initiation and progression. This highlights the Batf-IL-23R axis as a promising target for the development of innovative strategies for PCa prevention and treatment.

A novel sensitive fluorescent probe with double channels for highly effective recognition of biothiols.

Biothiols play a crucial role in maintaining redox balance in organisms, and anomalous levels of biothiols in human organs can lead to various sicknesses and biological disorders. This work developed a novel sensitive fluorescent probe TZ-NBD with double channels for highly efficient recognition of biothiols. TZ-NBD adopts 4-Chloro-7-nitrobenzofurazan (NBD-Cl) as the recognition moiety with simultaneous fluorescence output. By incorporating NBD-Cl with the other fluorophore, benzothiazole dihydrocyclopentachromene derivative (TZ-OH), the dual-channel sensitive fluorescence probe TZ-NBD was built. The existence of Cys/ Hcy could significantly trigger both the green and red fluorescent emissions, which were derived from fluorophores amine-substituted NBD and TZ-OH, respectively. While exposing to GSH, only the red-channel fluorescence signal could be detected, indicating the release of TZ-OH. The phenomena was mainly attributed to the fact that sulfur-substituted NBD has nearly no fluorescence, while amine-substituted NBD shows obvious green fluorescence. In our study, TZ-NBD exhibited dual-channel sensitivity, fast response, and excellent selectivity to biothiols in vitro. Moreover, TZ-NBD was favorably utilized for recognition of biothiols in vivo. We believe that the sensitive fluorescence probe with double channels can afford an alternate approach for monitoring biothiols in organisms and would be useful for studying diseases associated with biothiols.

Hydrogen Bond Organic Frameworks as Radical Reactors for Enhancement in ECL Efficiency and Their Ultrasensitive Biosensing.

Nowadays, electrochemiluminescence (ECL) efficiency of an organic emitter is closely related with its potential applications in food safety and environmental monitoring fields. In this work, 2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine (TATB) was self-assembled to form hydrogen bond organic frameworks (HOFs), which worked as ideal reactors to generate highly active oxygen-containing radicals, followed by linking with isoluminol (ILu) via amide bond (termed ILu-HOFs). After covalent assembly with aminated indium-tin oxide electrode (labeled NH2-ITO), the ECL efficiency of the ILu-HOFs NH2-ITO showed about a 23.4-time increase over that of ILu itself in the presence of H2O2. Meanwhile, the enhanced ECL mechanism was mainly studied by electron paramagnetic resonance, theoretical calculation, and electrochemistry. On the above foundation, an aptamer "sandwich" ECL biosensor was constructed for detecting isocarbophos (ICP) via in situ elimination of H2O2 with catalase-linked palladium nanocubes (CAT-Pd NCs). The as-built sensor showed a broad linear range (1 pM to 100 nM) and a low limit of detection (LOD) down to 0.4 pM, coupled with efficient assays of ICP in lake water and cucumber juice samples. This strategy provides an effective way for the synthesis of advanced ECL emitter, coupled by showing promising applications in environmental and food analysis.

Simultaneous determination of the four key fluoroquinolones and two antipsychotics in fish and shrimp by LC-MS/MS.

In this study, we developed and validated a liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) method used to simultaneously determine levels of four fluoroquinolones (ofloxacin, norfloxacin, lomefloxacin, and pefloxacin) and two antipsychotics (diazepam and methaqualone) in fish and shrimp. The samples were extracted with a mixture of anhydrous sodium sulfate and acetonitrile, and purified by C18 cartridge solid-phase extraction with an optimized eluent. The MS2 method was applied to recognize the molecular structure of these compounds according to a main fragmentation scheme. The key ions of identification and quantification were deduced from chemical structures. Multiple reaction monitoring was used to quantitatively analyse the compounds of interest. Satisfactory linearities were obtained (R2 ≥0.99) with the limits of quantitation (LOQs) ranging between 0.03 and 1.96 µg kg-1. The recoveries were 74-122%, with a relative standard deviation (RSD) below 4.9% for these compounds at the spiking level of three, five, and ten times the LODs, respectively. The LC-MS/MS method allows precise and sensitive determination of residues of six important banned veterinary drugs in fish and shrimp tissue. This methodological approach solved the problem imposed by the need for two or more analysis methods to analyse the compounds of interest described in this study.