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.

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.

Phytochrome-interacting factor (PIF) in rapeseed (Brassica napus L.): Genome-wide identification, evolution and expression analyses during abiotic stress, light quality and vernalization.

Phytochrome-interacting factors (PIFs) are members of basic helix-loop-helix (bHLH) transcription factors and the primary partners of phytochromes (PHY) in light signaling. PIFs interact with the Pfr forms of phytochrome to play an important role in the pathways of response to light and temperature in plants. In this study, 30, 12, and 16 potential PIF genes were identified in Brassica napus, Brassica rapa, Brassica oleracea, respectively, which could be divided into three subgroups. The Br/Bo/BnaPIF genes are intron-rich and similar to the PIF genes in Arabidopsis. However, unlike the AtPIFs that exist in multiple alternative-splicing forms, the majority of Br/Bo/BnaPIF genes have no alternative-splicing forms. A total of 52 Br/Bo/BnaPIF proteins have both the conserved active PHYB binding (APB) and bHLH domains. The Ka/Ks ratio revealed that most BnaPIFs underwent purifying selection. A promoter analysis found that light-related, abscisic acid-related and MYB-binding sites were the most abundant in the promoters of BnaPIFs. BnaPIF genes displayed different spatiotemporal patterns of expression and were regulated by light quality, circadian rhythms, cold, heat, and vernalization. Our results are useful for understanding the biological functions of PIF proteins in rapeseed.

Controllable synthesis of Fe3O4-based magneto-dielectric ternary nanocomposites and their enhanced microwave absorption properties.

In order to overcome the drawbacks of Fe3O4 composite samples and greatly increase their performance in microwave absorption, magnetic Fe3O4 spindles coated with dielectric SnO2 nanorods and MnO2 nanoflakes have been successfully synthesized by a four-step simple hydrothermal route. This rationally designed magneto-dielectric ternary nanocomposite will introduce multiple reflection and conductive losses caused by its special multilayer structure and the effective complementarity of dielectric loss and magnetic loss. Therefore, its absorbing performance can be greatly improved. It is notable that the as-prepared Fe3O4@SnO2@MnO2 nanocomposites show a minimum reflection loss value of -50.40 dB at 17.92 GHz at a thickness of 3.9 mm and the absorption bandwidth ranges from 3.62 to 12.08 GHz. The as-prepared Fe3O4@SnO2@MnO2 ternary nanocomposite is expected to be a potential candidate for high-performance microwave-absorbing materials with intensive electromagnetic wave absorption and wide effective absorbing bandwidth.

Maternal genetic structure in ancient Shandong between 9500 and 1800 years ago.

Archaeological and ancient DNA studies revealed that Shandong, a multi-culture center in northern coastal China, was home to ancient populations having ancestry related to both northern and southern East Asian populations. However, the limited temporal and geographical range of previous studies have been insufficient to describe the population history of this region in greater detail. Here, we report the analysis of 86 complete mitochondrial genomes from the remains of 9500 to 1800-year-old humans from 12 archaeological sites across Shandong. For samples older than 4600 years before present (BP), we found haplogroups D4, D5, B4c1, and B5b2, which are observed in present-day northern and southern East Asians. For samples younger than 4600 BP, haplogroups C (C7a1 and C7b), M9 (M9a1), and F (F1a1, F2a, and F4a1) begin to appear, indicating changes in the Shandong maternal genetic structure starting from the beginning of the Longshan cultural period. Within Shandong, the genetic exchange is possible between the coastal and inland regions after 3100 BP. We also discovered the B5b2 lineage in Shandong populations, with the oldest Bianbian individual likely related to the ancestors of some East Asians and North Asians. By reconstructing a maternal genetic structure of Shandong populations, we provide greater resolution of the population dynamics of the northern coastal East Asia over the past nine thousand years.

Extended Working Frequency of Ferrites by Synergistic Attenuation through a Controllable Carbothermal Route Based on Prussian Blue Shell.

One of the major hurdles of ferrite-based microwave absorbing materials is the limited working frequency that urgently calls for an effective modification technique. Herein, a controllable carbothermal route has been developed to ameliorate the microwave absorption performance of Fe3O4 nanospheres by using metal-organic frameworks (MOFs) shell as a carbon source with changing ramping rates. An enhanced synergistic attenuation induced by varied composition and tailored morphology is of great importance, which can be regarded as the superiority of the comprehensive (magnetic and dielectric), rather than unilateral (dielectric), modification technique. The drawbacks of dielectric modification can be concluded as the separated attenuation mechanisms at discrete frequencies, proven by the construction of the core-shell structured Fe3O4@Prussian blue composite. The advantages of magnetic modification can also be confirmed by a series of Fe-based composites with unique composition and tailored structure derived from the Fe3O4@Prussian blue composite at a distinct heating rate. Further, the superiority can be summarized as the rearrangement of magnetic loss by exceeding the Snoek limit and the reinforcement of dielectric loss by enhancing the electrical conductivity and introducing multiple polarization processes. Consequently, the sample obtained at 10 °C min-1, which contains Fe and Fe3O4, shows an extended working frequency of 14.05 GHz, with a thickness less than 5 mm and a high reflection loss value of -48.04 dB at 1.55 mm. This work not only offers a novel carbothermal route based on MOFs coating to prepare desired magnetic composites, but also acquires deeper insights of the comprehensive modification technique, which may pave the way for designing high-performance electromagnetic devices.

Preliminary study of urine metabolism in type two diabetic patients based on GC-MS.

OBJECTIVE: Comparative study of type 2 diabetes and healthy controls by metabolomics methods to explore the pathogenesis of Type II diabetes. METHODS: Gas chromatography - mass spectrometry (GC-MS) with a variety of multivariate statistical analysis methods to the healthy control group 58 cases, 68 cases of Type II diabetes group were analyzed. Chromatographic conditions: DB-5MS column; the carrier gas He; flow rate of 1 mL·min(-1), the injection volume 1 uL; split ratio is 100: 1. MS conditions: electron impact (EI) ion source, an auxiliary temperature of 280°C, the ion source 230°C, quadrupole 150°C; mass scan range 30~600 mAu. RESULTS: Established analytical method based on urine metabolomics GC-MS of Type II diabetes, determine the urine succinic acid, L-leucine, L-isoleucine, tyrosine, slanine, acetoace acid, mannose, L-isoleucine, L-threonine, Phenylalanine, fructose, D-glucose, palmi acid, oleic acid and arachidonic acid were significantly were significantly changed. CONCLUSION: Based on metabolomics of GC-MS detection and analysis metabolites can be found differences between type 2 diabetes and healthy control group, PCA diagram can effectively distinguish Type II diabetes and healthy control group, with load diagrams and PLS-DA VIP value metabolite screening, the resulting differences in metabolic pathways involved metabolites, including amino acid metabolism, lipid metabolism, glucose metabolism and energy metabolism.