Heterozygous Spink1 c.194+2T>C mutation promotes chronic pancreatitis after acute attack in mice.

BACKGROUND & AIMS: Mutations in genes, including serine protease inhibitor Kazal-type 1 (SPINK1), influence disease progression following sentinel acute pancreatitis event (SAPE) attacks. SPINK1 c.194+2T > C intron mutation is one of the main mutants of SPINK1，which leads to the impairment of SPINK1 function by causing skipping of exon 3. Research on the pathogenesis of SAPE attacks would contribute to the understanding of the outcomes of acute pancreatitis. Therefore, the aim of the study was to clarify the role of SPINK1 c.194+2T > C mutation in the CP progression after an AP attack. METHODS: SAPE attacks were induced in wildtype and SPINK mutant (Spink1 c.194+2T > C) mice by cerulein injection. The mice were sacrificed at 24 h, 14 d, 28 d, and 42 d post-SAPE. Data-independent acquisition (DIA) proteomic analysis was performed for the identification of differentially expressed protein in the pancreatic tissues. Functional analyses were performed using THP-1 and HPSCs. RESULTS: Following SAPE attack, the Spink1 c.194+2T > C mutant mice exhibited a more severe acute pancreatitis phenotype within 24 h. In the chronic phase, the chronic pancreatitis phenotype was more severe in the Spink1 c.194+2T > C mutant mice after SAPE. Proteomic analysis revealed elevated IL-33 level in Spink1 c.194+2T > C mutant mice. Further in vitro analyses revealed that IL-33 induced M2 polarization of macrophages and activation of pancreatic stellate cells. CONCLUSION: Spink1 c.194+2T > C mutation plays an important role in the prognosis of patients following SAPE. Heterozygous Spink1 c.194+2T > C mutation promotes the development of chronic pancreatitis after an acute attack in mice through elevated IL-33 level and the induction of M2 polarization in coordination with pancreatic stellate cell activation.

A double methylene blue labeled single-stranded DNA and hairpin DNA coupling biosensor for the detection of Fusarium oxysporum f. sp. cubense race 4.

The DCL gene in Fusarium oxysporum f. sp. cubense Race 4 (Foc4) is a pivotal pathogenic factor causing banana fusarium wilt. Precise DCL detection is crucial for Foc4 containment. Here, we present a novel ssDNA-hDNA coupling electrochemical biosensor for highly specific DCL detection. The sensing interface was formed via electrodeposition of a composite containing reduced graphene oxide (rGO) and gold nanoparticles (AuNPs) onto a carbon screen-printed electrode (SPE), followed by thiol-modified ssDNA functionalization. Additionally, the incorporation of hDNA, with methylene blue (MB) at both ends, binds to ssDNA through base complementarity, forming an ssDNA-hDNA coupling probe with bismethylene blue. This sensing strategy relies on DCL recognition by the hDNA probe, leading to DNA hairpin unfolding and detachment of hDNA bearing two MBs from ssDNA, generating a robust "on-off" signal. Empirical results demonstrate the sensor's amplified electrical signals, reduced background currents, and an extended detection range (6.02 × 106-3.01 × 1010 copies/µL) with a limit of detection (3.01 × 106 copies/µL) for DCL identification. We applied this sensor to analyze soil, banana leaves, and fruit samples, confirming its high specificity and stability. Moreover, post-sample detection, the sensor exhibits reusability, offering a cost-effective and rapid approach for banana wilt detection.

Identification of novel factors that affect the onset of idiopathic chronic pancreatitis: The role for microRNA-323b-5p.

BACKGROUND: The c.194+2 T>C variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear. METHODS: Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively. RESULTS: Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3. CONCLUSIONS: The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.

Immobilized Ag3PO4/GO on 3D nickel foam and its photocatalytic degradation of norfloxacin antibiotic under visible light.

In this study, a series of Ag3PO4/graphene oxide (GO) films were dip-coated on a metal nickel foam. The immobilized catalysts were characterized by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, Raman spectroscopy, high-resolution transmission electron microscopy and photoluminescence spectroscopy. The results show that Ag3PO4/GO was successfully supported on a nickel foam. The photocatalytic activity of the film catalyst under visible light was investigated by the degradation of norfloxacin, an antibiotic. Photocatalytic stability of this catalyst was also investigated. An optimized film exhibited superior activity and stability, the degradation rate of norfloxacin was about 83.68% in 100 min and the reaction rate constant k was 1.9 times that of pristine Ag3PO4. Further investigation found that photo-generated holes (h+) and superoxide anion radicals (·O2 -) are the main active species in the photodegradation process. The result indicates that the addition of GO inhibits the recombination of photogenerated electron-hole pairs, and thus has improved the photocatalytic activity and cyclic stability under visible light. The photocatalytic mechanism of the film catalyst was proposed. The prepared Ag3PO4/GO film catalyst is a promising candidate for treatment of wastewater containing antibiotics.

WO3/p-Type-GR Layered Materials for Promoted Photocatalytic Antibiotic Degradation and Device for Mechanism Insight.

Graphene enhanced WO3 has recently become a promising material for various applications. The understanding of the transfer of charge carriers during the photocatalytic processes remains unclear because of their complexity. In this study, the characteristics of the deposited WO3/graphene layered materials were investigated by Raman spectroscopy, UV-vis spectroscopy, and SEM. According to the results, p-graphene exhibits and enhances the characteristics of the WO3/graphene film. The photocatalytic activities of WO3/graphene layered materials were assessed by the photocatalytic degradation of oxytetracycline antibiotics as irradiated by UV light. Here, a higher current of cyclic voltammetry and a higher resistance of impedance spectra were obtained with the as-grown WO3/graphene directly synthesized on Cu foils under UV light using an electrochemical method, which was different from traditional WO3 catalysts. Thus, it is urgent to explore the underlying mechanism in depth. In this study, a large layered material WO3/graphene was fabricated on a Si substrate using a modified CVD method, and a WO3/graphene device was developed by depositing a gold electrode material and compared with a WO3 device. Due to photo-induced doping effects, the current-voltage test suggested that the photo-resistance is larger than dark-resistance, and the photo-current is less than the dark current based on WO3/graphene layered materials, which are significantly different from the characteristics of the WO3 layered material. A new pathway was developed here to analyze the transfer properties of carriers in the photocatalytic process.