PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway.

Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase ß1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.

miR171-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 regulate somatic embryogenesis in citrus.

Somatic embryogenesis (SE) is a key regeneration pathway in various biotechnology approaches to crop improvement, especially for economically important perennial woody crops like citrus. However, maintenance of SE capability has long been a challenge and becomes a bottleneck in biotechnology-facilitated plant improvement. In the embryogenic callus (EC) of citrus, we identified 2 csi-miR171c-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 (CsSCL2/3), which exert positive feedback regulation on csi-miR171c expression. Suppression of CsSCL2 expression by RNA interference (RNAi) enhanced SE in citrus callus. A thioredoxin superfamily protein CsClot was identified as an interactive protein of CsSCL2/3. Overexpression of CsClot disturbed reactive oxygen species (ROS) homeostasis in EC and enhanced SE. Chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-Seq identified 660 genes directly suppressed by CsSCL2 that were enriched in biological processes including development-related processes, auxin signaling pathway, and cell wall organization. CsSCL2/3 bound to the promoters of regeneration-related genes, such as WUSCHEL-RELATED HOMEOBOX 2 (CsWOX2), CsWOX13, and Lateral Organ Boundaries Domain 40 (LBD40), and repressed their expression. Overall, CsSCL2/3 modulate ROS homeostasis through the interactive protein CsClot and directly suppress the expression of regeneration-related genes, thus regulating SE in citrus. We uncovered a regulatory pathway of miR171c-targeted CsSCL2/3 in SE, which shed light on the mechanism of SE and regeneration capability maintenance in citrus.

Impact of baseline body composition on prognostic outcomes in urological malignancies treated with immunotherapy: a pooled analysis of 10 retrospective studies.

OBJECTIVE: Numerous epidemiological investigations have explored the impact of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in urological malignancies (UM) patients, yielding conflicting findings. As a result, our study aims to elucidate the influence of baseline body composition on the long-term prognosis of UM patients treated with ICIs. METHODS: We employed a rigorous systematic search across various databases, including PubMed, Embase, the Cochrane Library, and Google Scholar, to identify studies meeting our inclusion criteria. Our primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS). RESULTS: This analysis included a total of 10 articles with a combined patient cohort of 707 individuals. Our findings revealed a noteworthy association between several body composition parameters and unfavorable OS outcomes, including low psoas muscle index (PMI; HR: 3.88, p < 0.001), low skeletal muscle index (SMI; HR: 1.63, p < 0.001), sarcopenia (HR: 1.88, p < 0.001), low visceral adipose index (VAI; HR: 1.38, p = 0.018) and low subcutaneous adipose index (SAI; HR: 1.37, p = 0.018). Furthermore, our analysis demonstrated that low PMI (HR: 2.05, p = 0.006), low SMI (HR: 1.89, p = 0.002), sarcopenia (HR: 1.80, p < 0.001), and low VAI (HR:1.59, p = 0.005) were significantly correlated with inferior PFS. Conversely, SAI did not manifest a pronounced association with PFS in UM patients treated with ICIs. CONCLUSION: Collectively, our study findings underscore a substantial relationship between baseline body composition and reduced clinical efficacy in UM patients undergoing ICI therapy.

Expression characteristics and inhibitory activity of a leucine-rich repeat (LRR)-only protein in the Chinese mitten crab, Eriocheir sinensis.

The leucine-rich repeat (LRR) domain is a crucial structure in a variety of immune related proteins and displays multiple immune functions. In this study, the open reading frame (ORF) of an LRR-only protein was cloned from the Chinese mitten crab, Eriocheir sinensis (EsLRRop1). The protein sequence of EsLRRop1 contained seven LRR motifs, three LRR-TYP motifs and an LRRCT motif. Tissue distribution exhibited that EsLRRop1 mainly expressed in nervous tissues including thoracic ganglion, eyestalk and brain while showed relatively lower transcriptional level in hemocyte. Based on the above expression characteristics, the responses of EsLRRop1 to the challenge of Vibrio parahaemolyticus and Staphylococcus aureus were tested. The result showed that the transcript of EsLRRop1 in thoracic ganglion and eyestalk up-regulated after being challenged with S. aureus, while it decreased post injection with V. parahaemolyticus. The transcript of EsLRRop1 in hemocytes up-regulated sharply at 3 h and decreased at 12 h and 24 h after being challenged with V. parahaemolyticus, while it decreased at 12 h and 24 h post injection with S. aureus. The recombinant protein of EsLRRop1 (His-EsLRRop1) displayed binding activities to V. alginolyticus, V. harveyi, V. parahaemolyticus, S. aureus, Corynebacterium glutamicum and Micrococcus lysodeikticus as well as lipopolysaccharide (LPS) and peptidoglycan (PGN). Moreover, the His-EsLRRop1 exhibited inhibitory activity against V. parahaemolyticus and V. harveyi with minimum inhibitory concentration (MIC) of 3.57-7.14 µM and 7.14-14.28 µM, respectively. These results provide theoretical basis for the application of EsLRRop1 in inhibiting bacteria in aquaculture practice.

Nomogram prediction for periodontitis in Chinese pregnant women with different sociodemographic and oral health behavior characteristics: a community-based study.

BACKGROUND: Periodontitis is associated with poor pregnancy outcomes, indicating periodontal health as an important health concern for pregnant women. Herein, this study identified risk indicators for periodontitis and developed a nomogram for predicting the risk of periodontitis in pregnancy by analyzing periodontitis and associated factors in pregnant women. MATERIALS AND METHODS: A community-based cross-sectional study was conducted by including 438 pregnant women at 10-36 gestational weeks from Langfang, China. Pregnant women were examined for periodontal status, and their demographic, socioeconomic, and oral health behavior data were collected. Potential influencing factors of periodontitis were analyzed with univariate and multivariate logistic regression analyses. A nomogram was developed, followed by the assessment of its validation and discriminatory abilities. RESULTS: The prevalence of periodontitis was 59.8% in pregnant women. Periodontitis-associated variables in pregnant women were gestational age, non-first pregnancy, daily tooth brushing frequency of ≤ 1 before pregnancy, and annual frequency of periodontal treatment < 1 (including no periodontal treatment). The risk of periodontitis was positively associated with gestational age (OR = 1.28, 95% CI = 1.17-1.39, p < 0.001). Pregnancy history showed a strong positive association (OR = 6.57, 95% CI = 1.22-35.43, p = 0.03). Daily tooth brushing frequency before pregnancy was also positively associated with periodontitis (OR = 1.54, 95% CI = 1.03-2.79, p = 0.05). Additionally, the annual frequency of periodontal treatment exhibited a positive association, with higher odds observed for those with less frequent treatment (OR = 2.28, 95% CI = 1.25-4.14, p = 0.05; OR = 7.37, 95% CI = 3.04-22.06, p < 0.001). These four factors were used to develop a nomogram for predicting periodontitis in pregnant women. The area under the receiver operating characteristic curve of the nomogram was 0.855 and 0.831 in the training and testing cohorts, respectively, reflecting the superior prediction accuracy of the nomogram. The calibration curve and decision curve analysis demonstrated the good performance and net benefit of the nomogram. CONCLUSION: Risk factors for periodontitis in pregnant Chinese women include gestational age, non-first pregnancy, lower frequency of daily tooth brushing before pregnancy, and lower frequency of periodontal treatment. An easy-to-use nomogram with acceptable accuracy can allow for the prediction of periodontitis risk in pregnant Chinese women. CLINICAL RELEVANCE: With the assistance of this nomogram, clinicians can evaluate the risk of periodontitis in pregnancy, thereby offering more tailored oral health education to women of reproductive age.

Genome-wide characterization of long terminal repeat retrotransposons provides insights into trait evolution of four cucurbit species.

Cucurbits are a diverse plant family that includes economically important crops, such as cucumber, watermelon, melon, and pumpkin. Knowledge of the roles that long terminal repeat retrotransposons (LTR-RTs) have played in diversification of cucurbit species is limited; to add to understanding of the roles of LTR-RTs, we assessed their distributions in four cucurbit species. We identified 381, 578, 1086, and 623 intact LTR-RTs in cucumber (Cucumis sativus L. var. sativus cv. Chinese Long), watermelon (Citrullus lanatus subsp. vulgaris cv. 97103), melon (Cucumis melo cv. DHL92), and Cucurbita (Cucurbita moschata var. Rifu), respectively. Among these LTR-RTs, the Ale clade of the Copia superfamily was the most abundant in all the four cucurbit species. Insertion time and copy number analysis revealed that an LTR-RT burst occurred approximately 2 million years ago in cucumber, watermelon, melon, and Cucurbita, and may have contributed to their genome size variation. Phylogenetic and nucleotide polymorphism analyses suggested that most LTR-RTs were formed after species diversification. Analysis of gene insertions by LTR-RTs revealed that the most frequent insertions were of Ale and Tekay and that genes related to dietary fiber synthesis were the most commonly affected by LTR-RTs in Cucurbita. These results increase our understanding of LTR-RTs and their roles in genome evolution and trait characterization in cucurbits.

Topological Wannier cycles induced by sub-unit-cell artificial gauge flux in a sonic crystal.

Gauge fields play a major role in understanding quantum effects. For example, gauge flux insertion into single unit cells is crucial towards detecting quantum phases and controlling quantum dynamics and classical waves. However, the potential of gauge fields in topological materials studies has not been fully exploited. Here, we experimentally demonstrate artificial gauge flux insertion into a single plaquette of a sonic crystal with a gauge phase ranging from 0 to 2π. We insert the gauge flux through a three-step process of dimensional extension, engineering a screw dislocation and dimensional reduction. Additionally, the single-plaquette gauge flux leads to cyclic spectral flows across multiple bandgaps that manifest as topological boundary states on the plaquette and emerge only when the flux-carrying plaquette encloses the Wannier centres. We termed this phenomenon as the topological Wannier cycle. This work paves the way towards sub-unit-cell gauge flux, enabling future studies on synthetic gauge fields and topological materials.

The effects of sodium sulfite on Helicobacter pylori by establishing a hypoxic environment.

Helicobacter pylori (H. pylori) is an obligate microaerobion and does not survive in low oxygen. Sodium sulfite (SS) reacts and consume oxygen in solutions. The present study aimed to investigate the effects of SS on H. pylori. The effects of SS on oxygen concentrations in solutions and on H. pylori in vivo and in vitro were examined, and the mechanisms involved were explored. The results showed that SS decreased the oxygen concentration in water and artificial gastric juice. In Columbia blood agar and special peptone broth, SS concentration-dependently inhibited the proliferation of H. pylori ATCC43504 and Sydney strain-1 in Columbia blood agar or special peptone broth, and dose-dependently decreased the number of H. pylori in Mongolian gerbils and Kunming mouse infection models. The H. pylori was relapsed in 2 weeks withdrawal and the recurrence in the SS group was lower than that in the positive triple drug group. These effects were superior to positive triple drugs. After SS treatments, the cell membrane and cytoplasm structure of H. pylori were disrupted. SS-induced oxygen-free environment initially blocked aerobic respiration, triggered oxidative stress, disturbed energy production. In conclusion, SS consumes oxygen and creates an oxygen-free environment in which H. pylori does not survive. The present study provides a new strategy and perspective for the clinical treatment of H. pylori infectious disease.

Incidence and risk factors of fasting hyperglycaemia following first-attack acute pancreatitis before discharge: a retrospective study.

BACKGROUND: Pancreatic endocrine insufficiency is more likely to occur after acute pancreatitis (AP), but the risk factors affecting pancreatic endocrine function remain controversial. Therefore, exploring the incidence and risk factors of fasting hyperglycaemia following first-attack AP is important. METHODS: Data were collected from 311 individuals with first-attack AP without previous diabetes mellitus (DM) or impaired fasting glucose (IFG) history treated in the Renmin Hospital of Wuhan University. Relevant statistical tests were performed. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: The incidence of fasting hyperglycaemia in individuals with first-attack AP was 45.3%. Univariate analysis showed that age (χ2 = 6.27, P = 0.012), aetiology (χ2 = 11.184, P = 0.004), serum total cholesterol (TC) (χ2 = 14.622, P < 0.001), and serum triglyceride (TG) (χ2 = 15.006, P < 0.001) were significantly different between the hyperglycaemia and non-hyperglycaemia groups (P < 0.05). The serum calcium concentration (Z=-2.480, P = 0.013) was significantly different between the two groups (P < 0.05). Multiple logistic regression analysis showed that age- ≥60 years (P < 0.001, OR = 2.631, 95%Cl = 1.529-4.527) and TG ≥ 5.65 mmol/L (P < 0.001, OR = 3.964, 95%Cl = 1.990-7.895) were independent risk factors for fasting hyperglycaemia in individuals with first-attack AP (P < 0.05). CONCLUSIONS: Old age, serum triglycerides, serum total cholesterol, hypocalcaemia, and aetiology are associated with fasting hyperglycaemia following first-attack AP. Age ≥ 60 years and TG ≥ 5.65 mmol/L are independent risk factors for fasting hyperglycaemia following first-attack AP.

Thermal conductivity of fivefold twinned silicon-germanium heteronanowires.

The thermal transport properties of five-fold twinned (5FT) germanium-silicon (Ge-Si) heteronanowires (h-NWs) with varying cross-sectional areas, germanium (Ge) domain ratios and heterostructural patterns are investigated using homogeneous nonequilibrium molecular dynamics (HNEMD) simulations. The results demonstrate a distinctive behavior in the thermal conductivity (κ) of 5FT-NWs, characterized by a "flipped" trend at a critical cross-sectional area. This behavior is attributed to the hydrodynamic phonon flow, arising from the normal three-phonon scattering process in the low-frequency region. In addition, the composition ratio of 5FT-NWs has a significant impact on reducing the κ of 5FT-NWs and suppressing the hydrodynamic effect. Intriguingly, as the homogeneous element domains are separated, stronger phonon hydrodynamic flows are observed in comparison to the adjacent homogeneous element domains. By analyzing various phonon properties, including phonon dispersion, three-phonon scattering rate, and phonon mean free path, critical insights into the origin of the differential κ in different 5FT-NW structures are provided. The findings deepen the understanding of the thermal transport properties of nanomaterials and hold implications for the design and development of nanoelectronics and thermoelectric devices.

Association between copy number variation of SERPINA3-1 gene and growth traits in Chinese cattle.

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3) belongs to the serine protease inhibitor family A subtype, and contains 8 genes from SERPINA3-1 to SERPINA3-8. Although the regulatory effects of these 8 genes have been revealed one by one in recent years, the related effects of SERPINA3-1 gene on cattle growth is still unclear. This study used quantitative Real time PCR (qPCR) to detect the type of copy number variation (CNV) of SERPINA3-1 gene in a total of 542 Chinese cattle, and expression of SERPINA3-1 gene in different tissues of Qinchuan cattles (adult) on mRNA level. Then association analysis was conducted between the detection results and cattle growth traits. The results showed that the Duplication type in SERPINA3-1 gene performed better on the growth traits and the CNV was significantly correlated with multiple growth traits (p < 0.05). In addition, SERPINA3-1 gene has different expression conditions in different tissues, results showed that SERPINA3-1 gene has a low expression in muscle. In conclusion, we speculate that the SERPINA3-1 gene can be used as a molecular marker and the result of this study could be a basic material for candidate functional genes for beef cattle growth and development.

In order to detect the gene expression diversification of the SERPINA3-1 gene, blood samples were collected from five Chinese cattle breeds, we detected related signal and made an associated analyze with cattle growth traits. We determined the copy number variation distribution of the SERPINA3-1 gene in cattle populations and found that the SERPINA3-1 gene has a certain promoting effect on the growth and development of Chinese cattle. For example, Pinan cattle with Duplication type copy number have a better performance on growth traits. This study has enriched the candidate genes of Chinese cattle molecular breeding and provided basic data for Chinese cattle breeding.

Correlation between microbial communities and key odourants in fermented capsicum inoculated with Pediococcus pentosaceus and Cyberlindnera rhodanensis.

BACKGROUND: Fermented capsicum (i.e. pickled pepper) is one of the most popular fermented vegetables. However, the effect of inoculated microbial fermentation on pickled pepper is not yet fully understood. RESULTS: Cyberlindnera rhodanensis J52 with a rich ester flavour and Pediococcus pentosaceus AL with a strong inhibitory effect on foodborne pathogenic bacteria were selected to prepare single- and double-strain fermented capsicum under low salt (< 10 g L-1 sodium chloride) conditions. The inhibition zone of P. pentosaceus AL against Escherichia coli was up to 44 mm in diameter. Biochemical indicator analyses found that co-fermentation of P. pentosaceus AL and C. rhodanensis J52 changed the contents of vitamin C and short-chain fatty acids. Analysis of microbial diversity and volatile metabolome showed that 125 microbial species and 72 volatile compounds were detected, and P. pentosaceus was the dominant bacterium that inhibited the growth of other bacteria, while C. rhodanensis was the fungus that contributed the most to flavour. Correlation analysis between microorganisms and flavour compounds showed 725 correlations, and 124 microbial species may have participated in the formation of 69 compounds. Furthermore, 10 and 29 correlations were detected between P. pentosaceus AL or C. rhodanensis J52 and flavour compounds, respectively. Among them, 3-methyl-1-butanol acetate is speculated to be the main substance affecting the flavour of fermented capsicum by inoculation with C. rhodanensis J52. CONCLUSION: The inoculation of P. pentosaceus and C. rhodanensis had a significant impact on the microbial community and volatile compounds of fermented capsicum and helped to improve its organoleptic qualities. © 2022 Society of Chemical Industry.

Inhibition of Notch activity suppresses hyperglycemia-augmented polarization of macrophages to the M1 phenotype and alleviates acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory disorder characterized by acinar cell death and inflammation. Multiple factors cause hyperglycemia after AP. Macrophage polarization is involved in tissue injury and repair, and is regulated by Notch signaling during certain inflammatory diseases. The present study explores the relationship among hyperglycemia, macrophage polarization, and Notch signaling during AP and the related mechanisms. A cerulein-induced AP model was established in FVB/N mice, and AP with hyperglycemia was initiated by injection of 50% concentration glucose. Tissue damage, Notch activity, and macrophage polarization were assessed in pancreatic tissues. The role of Notch signaling in macrophage polarization during AP was also assessed in vitro by co-culturing primary macrophages and pancreatic acinar cells, and establishing a lipopolysaccharide (LPS)-induced inflammatory model in RAW264.7 cells. Pancreatic acinar cells were damaged and proinflammatory factor levels were increased in pancreatic tissues during AP. The hyperglycemic conditions aggravated pancreatic injury, increased macrophage infiltration, promoted macrophage polarization towards an M1 phenotype, and led to excessive up-regulation of Notch activity. Inhibition of Notch signaling by DAPT or Notch1 knockdown decreased the proportion of M1 macrophages and reduced the production of proinflammatory factors, thus mitigating pancreatic injury. These findings suggest that hyperglycemia induces excessive Notch signaling after AP and further aggravates AP by promoting pancreatic macrophage polarization towards the M1 phenotype. The Notch signaling pathway is a potential target for the prevention and treatment of AP.

A formal [4 + 2] annulation of diamines and prop-2-ynyl sulfonium salts for the synthesis of tetrahydroquinoxalines.

A formal [4 + 2] annulation of diamines and prop-2-ynyl sulfonium salts was developed. This strategy enables efficient access to tetrahydroquinoxalines in excellent yields.

Role of mechanical deformation in the thermal transport of sI-type methane hydrate.

Natural gas hydrates (NGHs) are rising as an unconventional energy resource. The fundamental thermal characteristics of NGHs are of importance for natural gas exploitation from permafrost and oceanic sediments that are geomechanically deformed. Here, utilizing classic molecular dynamics simulations with all-atom (AA) and coarse-grained (CG) models of the methane guest molecule, the effects of mechanical strain on the thermal conductivity of sI-type methane hydrate are for the first time examined. Upon triaxial tension and compression, methane hydrate exhibits strong asymmetry in the stress responses. As the triaxial loads go from compression to tension, a reduction trend in the thermal conductivity is revealed for methane hydrate with both AA and CG models of methane, within a maximum reduction of over 44%. This reduction is because triaxial strain from compression to tension softens the phonon modes. Interestingly, there is a sudden rise in thermal conductivity at critical triaxial strain of 0.06, originating from that, at which, the phonon modes are hardened and the peaks of radial distribution functions are shifted back. This study provides important information on the thermal conductivity of methane hydrate, which is helpful for the practical production of natural gas from geo-deformed NGH-bearing sediments via a heating technique as well as evaluating their stability.

miR171 modulates induction of somatic embryogenesis in citrus callus.

KEY MESSAGE: Overexpression of miR171 restored SE competence in the recalcitrant citrus callus, and inhibition of miR171 function weakened SE competence in the strongly embryogenic citrus callus. Somatic embryogenesis (SE) is an important way of in vitro regeneration for plants. For perennial woody crops such as citrus, embryogenic callus is usually induced from unfertilized aborted ovules and widely used in biotechnology aided breeding. However, SE capacity always declines in callus during subculture, which makes regeneration difficult and hinders the application of biotechnology. We previously found that miR171 may be a regulator of SE in citrus, based on the abundant expression of csi-miR171c in the embryogenic callus and during SE of citrus. Here, we report that miR171 promotes SE and is required for SE in citrus. Overexpression of miR171 restored SE competence in the recalcitrant callus of 'Guoqing No.1' Satsuma mandarin (G1), whereas inhibition of miR171 function by Short Tandem Target Mimic (STTM) weakened SE competence in the strongly embryogenic callus of 'Valencia' sweet orange (V). The comparative transcriptomic analysis in miR171 overexpressed callus line (OE) and the wild type callus (WT) indicated that overexpression of miR171 decreased the expression level of its SCARECROW-LIKE (CsSCL) targets, and activated stress response related biological processes and metabolic processes that are required for cell differentiation. However, CsSCLs were up-regulated in the OE callus during SE induction process, which activated the cell division and developmental processes that are required for embryogenesis progress. Our results validate the function of miR171 in regulation of SE and reveal the biological responses provoked by miR171 in citrus that may promote SE.

Circular RNA CDR1as promotes tumor progression by regulating miR-432-5p/E2F3 axis in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC), characterized with high growth rate and metastatic rate. It's urgently necessary to explore new mechanism of PC. Circular RNA/miRNA/mRNA network was widely reported to participate in the cancer progression. METHODS: In this research, circular RNA CDR1as (circCDR1as) was identified by microarray analysis and detected in pancreatic cancer (PC) tissues and cells. Transwell, colony-forming assay, nude mouse tumorigenicity assay were used to determine the function of circCDR1as in PC. Western blot, dual luciferase reporting test were applied to investigate the mechanism. RESULTS: We found that circCDR1as was highly expressed in PC tissues. The levels of circCDR1as in PC tissues and cells were higher than those in controls. CircCDR1as promoted the migration, invasion and proliferation of PC cells in vitro and tumor growth in vivo via mediating E2F3 expression by sponging miR-432-5p. CONCLUSIONS: In conclusion, circCDR1as could promote the development of PC and might be a novel diagnostic target for PC.

Long non-coding RNAs HERH-1 and HERH-4 facilitate cyclin A2 expression and accelerate cell cycle progression in advanced hepatocellular carcinoma.

BACKGROUND: The advanced hepatocellular carcinoma (HCC), such as the recurrent tumor after liver transplantation (LT), is an obstacle of HCC treatment. The aim of this study was to discover the underlying mechanism of HCC progression caused by non-coding RNAs (ncRNAs). METHODS: To this end, we investigated the selected patient cohort of matching primary and recurrent HCC after receiving LT. The recurrent tumors after LT were regarded as clinical models of the advanced HCC. Microarrays were used to profile lncRNA and mRNA expression in HCC recurrent and primary tissue samples. The mRNA profile characteristics were analyzed by bioinformatics. Two cell lines, HepG2 and QGY-7703, were used as HCC cell models. The protein-coding potential, length, and subcellular location of the interested lncRNAs were examined by bioinformatics, Northern blot, fluorescent in situ hybridization (FISH), and quantitative RT-PCR (qRT-PCR) assays. HCC cell proliferation was detected by CCK-8, doubling time and proliferation marker gene quantitation assays. DNA replication during the cell cycle was measured by EdU/PI staining and flow cytometry analyses. Promoter activity was measured using a luciferase reporter assay. Interactions between DNA, RNA, and protein were examined by immunoprecipitation and pull-down assays. The miRNA-target regulation was validated by a fluorescent reporter assay. RESULTS: Both lncRNA and mRNA profiles exhibited characteristic alterations in the recurrent tumor cells compared with the primary HCC. The mRNA profile in the HCC recurrent tissues, which served as model of advanced HCC, showed an aberrant cell cycle regulation. Two lncRNAs, the highly expressed lncRNA in recurrent HCC (HERH)-1 and HERH-4, were upregulated in the advanced HCC cells. HERH-1/4 enhanced proliferation and promoted DNA replication and G1-S transition during the cell cycle in HCC cells. HERH-1 interacted with the transcription factor CREB1. CREB1 enhanced cyclin A2 (CCNA2) transcription, depending on HERH-1-CREB1 interaction. HERH-4 acted as an miR-29b/c sponge to facilitate CCNA2 protein translation through a competing endogenous RNA (ceRNA) pathway. CONCLUSIONS: The oncogenic lncRNA HERH-1/4 promoted CCNA2 expression at the transcriptional and post-transcriptional levels and accelerated cell cycle progression in HCC cells. The HERH-1-CREB1-CCNA2 and HERH-4-miR-29b/c-CCNA2 axes served as molecular stimuli for HCC advance.

Evaluation of the Relationship among Biogenic Amines, Nitrite and Microbial Diversity in Fermented Mustard.

Biogenic amines (BAs) and nitrites are both considered harmful compounds for customer health, and are closely correlated with the microorganisms in fermented mustard (FM). In this study, BAs and nitrite contents in fifteen FM samples from different brands were analyzed. The concentrations of cadaverine in one sample and of histamine in one sample were above the toxic level. Moreover, five FM samples contained a high level of nitrite, exceeding the maximum residue limit (20 mg/kg) suggested by the National Food Safety Standard. Then, this study investigated bacterial and fungal communities by high-throughput sequencing analysis. Firmicutes and Basidiomycota were identified as the major bacteria and fungi phylum, respectively. The correlations among microorganisms, BAs and nitrite were analyzed. Typtamine showed a positive correlation with Lactobacillus and Pseudomonas. Cadaverine and nitrite is positively correlated with Leuconostoc. Furthermore, thirteen strains were selected from the samples to evaluate the accumulation and degradation properties of their BAs and nitrite. The results indicated that the Lactobacillus isolates, including L. plantarum GZ-2 and L. brevis SC-2, can significantly reduce BAs and nitrite in FM model experiments. This study not only assessed the contents of BAs and nitrite in FM samples, but also provided potential starter cultures for BAs and nitrite control in the FM products industry.

[Supergenes:Generalists in Gene Expression].

In eukaryote cells,transcription from genome DNA is a key process of gene expression.The transcription products contain not only messenger RNAs that code proteins,but also various types of non-coding RNAs.During transcription,some of the gene loci produce more than one kind of RNA molecule,including coding RNAs and more often non-coding RNAs.These gene loci that generate several kinds of RNA molecules are named supergenes.According to the transcription pattern,supergenes are divided into three types,known as types Ⅰ,Ⅱ and Ⅲ.In this review,we summarize the transcription pattern of each type of supergene,and exposit the role of these genes in cells.