Understanding soil microbial communities in agroecosystems has the potential to contribute to the improvement of agricultural productivity and sustainability. Effects of conversion from long-term wheat plantation to Jerusalem artichoke (JA) plantation on soil fungal communities were determined by amplicon sequencing of total fungal ITS regions. Quantitative PCR and PCR-denaturing gradient gel electrophoresis were also used to analyze total fungal and Trichoderma spp. ITS regions and Fusarium spp. Ef1α genes. Results showed that soil organic carbon was higher in the first cropping of JA and Olsen P was lower in the third cropping of JA. Plantation conversion changed soil total fungal and Fusarium but not Trichoderma spp. community structures and compositions. The third cropping of JA had the lowest total fungal community diversity and Fusarium spp. community abundance, but had the highest total fungal and Trichoderma spp. community abundances. The relative abundances of potential fungal pathogens of wheat were higher in the wheat field. Fungal taxa with plant growth promoting, plant pathogen or insect antagonistic potentials were enriched in the first and second cropping of JA. Overall, short-term conversion from wheat to JA plantation changed soil fungal communities, which is related to changes in soil organic carbon and Olsen P contents.

The purpose of this study was to analyze if there is a significant correlation between the results of diffusion-weighted imaging (DWI) and the expression of proliferating cell nuclear antigen (PCNA) in astrocytomas. The DWI scans of 19 different-grade astrocytomas were obtained on a 3 T magnetic resonance scanner. The average regional apparent diffusion coefficients (ADC) were measured. The positive expression of PCNA was determined immunohistochemically by using streptavidin-peroxidase complex staining, and was quantified by calculating its calibrated opacity density (COD) using an image analysis system. The average regional ADC and PCNA COD of low grade and high grade astrocytomas were compared. Correlations between regional ADC and PCNA COD were analyzed. The average regional ADC of high grade astrocytomas was significantly (t = 10.169, P = 0.000) less (0.687 ± 0.225 × 10-3 mm2/s) than that of low grade astrocytomas (1.572 ± 0.333 × 10-3 mm2/s). The PCNA COD (0.343 ± 0.052) of high grade astrocytomas was significantly (t=-7.858, P=0.000) greater than that (0.194 ± 0.012) of low grade astrocytomas. There were strong negative correlations between regional ADC and PCNA COD (r = -0.801, P = 0.000). The results demonstrated that DWI is helpful in evaluating cell proliferation and preoperatively grading astrocytomas by measuring regional ADC.

The objective of this systematic review was to conduct a more comprehensive literature search and meta-analysis of original studies to evaluate the efficacy and safety of the loop electrosurgical excision procedure (LEEP) versus cold-knife conization (CKC) in conservative surgical treatment of cervical adenocarcinoma in situ (ACIS) for women who have not completed childbearing.

The aim of this study was to investigate the potential role of PHRF1 in lung tumorigenesis. Western blot analysis was used to detect the expression of proteins. Quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, soft agar assay and tumor formation assay in nude mice were applied. Cell cycle distribution was analyzed by flow cytometry. The lower level of PHRF1 mRNA was observed in human lung cancer tissues than that in paracancerous tissues. The decreased expression of PHRF1 protein was observed in H1299 and H1650 cell lines than that in 16HBE and BEAS-2B cell lines. The decreased expression of PHRF1 protein was observed in malignant 16HBE cells compared to control cells. The reduced expression of PHRF1 protein was observed in mice lung tissues treated with BaP than that in control group. Overexpression of PHRF1 inhibited H1299 cell proliferation, colony formation in vitro and growth of tumor xenograft in vivo, and arrested cell cycle in G1 phase. The decreased expression of TGIF and c-Myc proteins and the increased expression of p21 protein were observed in H1299-PHRF1 cells compared with H1299-pvoid cells. In conclusion, our findings suggest that overexpression of PHRF1 attenuated the proliferation and tumorigenicity of non-small cell lung cancer cell line of H1299.

The gene encoding endoplasmic reticulum (ER) lipid raft-associated protein 2 (ERLIN2) is amplified in human breast cancers. ERLIN2 gene mutations were also found to be associated with human childhood progressive motor neuron diseases. Yet, an understanding of the physiological function and mechanism for ERLIN2 remains elusive. In this study, we reveal that ERLIN2 is a spatially and temporally regulated ER-microtubule-binding protein that has an important role in cell cycle progression by interacting with and stabilizing the mitosis-promoting factors. Whereas ERLIN2 is highly expressed in aggressive human breast cancers, during normal development ERLIN2 is expressed at the postnatal stage and becomes undetectable in adulthood. ERLIN2 interacts with the microtubule component α-tubulin, and this interaction is maximal during the cell cycle G2/M phase where ERLIN2 simultaneously interacts with the mitosis-promoting complex Cyclin B1/Cdk1. ERLIN2 facilitates K63-linked ubiquitination and stabilization of Cyclin B1 protein in G2/M phase. Downregulation of ERLIN2 results in cell cycle arrest, represses breast cancer proliferation and malignancy and increases sensitivity of breast cancer cells to anticancer drugs. In summary, our study revealed a novel ER-microtubule-binding protein, ERLIN2, which interacts with and stabilizes mitosis-promoting factors to regulate cell cycle progression associated with human breast cancer malignancy.

Today, obesity and nonalcoholic steatohepatitis are a worldwide epidemic, although how these syndromes are regulated with respect to lncRNAs remains largely unknown. Our previous studies have revealed important pathological features and molecular characteristics of nonalcoholic steatohepatitis in the minipig model, and in this study, we analyze the features of lncRNAs and their potential target genes. Minipig samples only from liver were analyzed using next-generation deep sequencing. In total, we obtained 585 million raw reads approximately 70.4 Gb of high quality data. After a strict five-step filtering process, 1,179 lncRNAs were identified, including 89 differentially expressed lncRNAs (P < 0.05) in the experiment group relative to the control group. The cis and trans analysis identified target genes that were enriched for specific GO terms (P < 0.01), including immune processes, chemokine activity, cytokine activity, and G-protein coupled receptor binding, which are closely related to nonalcoholic steatohepatitis. The predicted protein-coding targets of the differentially expressed lncRNAs were further analyzed, such as PPAR, FADS2, DGAT2, ACAA2, CYP2E1, ADH4, and Fos. This study reveals a wealth of candidate lncRNAs involved in NASH and their regulated pathways, which should facilitate further research into the molecular mechanisms of this disorder.

Increasing evidence has shown that aldehyde dehydrogenase 1A1 (ALDH1A1), a detoxifying enzyme, is responsible for chemoresistance in a variety of tumors. Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), chemoresistance is a common cause of treatment failure. This study aims to investigate the significance of ALDH1A1 expression and the mechanism by which ALDH1A1 is involved in the chemoresistance of DLBCL cells. ALDH1A1 expression was assessed in 88 DLBCL tissues by immunohistochemistry. The association between ALDH1A1 expression and outcome was evaluated. We also investigated the effect of ALDH1A1 on CHOP resistance in DLBCL cells using functional analysis. ALDH1A1 expression levels were upregulated in patients with stable or progressive disease after CHOP and its expression positively correlated with expression of STAT3 and p-STAT3. In keeping with these observations, ALDH1A1 expression was significantly associated with short survival of DLBCL patients who received CHOP chemotherapy. In functional assays in Pfeiffer cells, overexpression of ALDH1A1 conferred resistance to CHOP, while silencing of ALDH1A1 using short hairpin RNA had the opposite effect. Furthermore, we also observed that ALDH1A1 could regulate the JAK2/STAT3 pathway, while inhibition of the JAK2/STAT3 pathway by WP1066 negated the effect of ALDH1A1 overexpression. These observations reveal that ALDH1A1 induces resistance to CHOP through activation of the JAK2/STAT3 pathway in DLBCL, and its targeting provides a potential strategic approach for reversing CHOP resistance.

Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.

Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China.

This study aimed to address the potential role of STIM1 (stromal interaction molecule 1) in lung tumorigenesis. Colony formation in soft agar assay and tumorigenicity in nude mice assay were conducted. Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction were used to measure the STIM1 expression. The distribution of cell cycle was detected by flow cytometry assay. Our results showed that the expression of STIM1 mRNA was significantly higher in human lung tumors than that in adjacent non-neoplastic lung tissues. Significantly increased expression of STIM1 mRNA and protein was observed in 16HBE-benzo(a)pyrene (BaP) cells and in BaP-treated mice lung tissues compared with 16HBE-control cells and the control group, respectively. Silencing STIM1 inhibited the proliferation and colony formation of A549 cells in in vitro experiments, attenuated the growth of tumor xenografts of A549 cells in in vivo experiments and induced the arrest of cell cycle in the G1 phase. The markedly decreased expression of cyclin D1 protein was observed in A549-shRNA-STIM1 cells as compared to A549-shRNA-control cells. The markedly increased expression of p21 protein was observed in A549-shRNA-STIM1 cells as compared to A549-shRNA-control cells. The expression levels of β-catenin and TGIF proteins were lower in A549-shRNA-STIM1 cells than those in A549-shRNA-control cells. In conclusion, this study indicated that the elevated expression of STIM1 might be involved in lung tumorigenesis.

Atrichia and sparse hair phenotype cause distress to many patients. Ectodermal dysplasia-9 (ED-9) is a congenital condition characterized by hypotrichosis and nail dystrophy without other disorders, and Hoxc13 is a pathogenic gene for ED-9. However, mice carrying Hoxc13 mutation present several other serious disorders, such as skeletal defects, progressive weight loss and low viability. Mouse models cannot faithfully mimic human ED-9. In this study, we generated an ED-9 pig model via Hoxc13 gene knockout through single-stranded oligonucleotides (c.396C > A) combined with CRISPR/Cas9 and somatic cell nuclear transfer. Eight cloned piglets with three types of biallelic mutations (five piglets with Hoxc13c.396C > A/c.396C > A, two piglets with Hoxc13c.396C > A/c.396C > A + 1 and one piglet with Hoxc13Δ40/Δ40) were obtained. Hoxc13 was not expressed in pigs with all three mutation types, and the expression levels of Hoxc13-regulated genes, namely, Foxn1, Krt85 and Krt35, were decreased. The hair follicles displayed various abnormal phenotypes, such as reduced number of follicles and disarrayed hair follicle cable without normal hair all over the body. By contrast, the skin structure, skeleton phenotype, body weight gain and growth of Hoxc13 knockout pigs were apparently normal. The phenotypes of Hoxc13 mutation in pigs were similar to those in ED-9 patients. Therefore, Hoxc13 knockout pigs could be utilized as a model for ED-9 pathogenesis and as a hairless model for hair regeneration research. Moreover, the hairless pigs without other major abnormal phenotypes generated in this study could be effective models for other dermatological research because of the similarity between pig and human skins.

Obesity and type 2 diabetes mellitus (T2D) are known risk factors for colon cancer. Recent reports from a number of genome wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with obesity and T2D. Here we tested the hypothesis that these SNPs may also be associated with risk of colon cancer.

The ubiquitin-ligase Fbw7 acts as a tumor suppressor, targeting lots of proto-oncogenes for proteolysis. However, the exact role of Fbw7 in diffuse large B-cell lymphoma (DLBCL) development remains unclear.

Intervertebral disc (IVD) degeneration is considered a common cause of low back pain. In the degenerating IVD, the production of pro-inflammatory cytokines, including IL-1 and TNF-α, progressively increases, contributing to the degenerative process. Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 enzymes, act as autocrine and paracrine effectors in regulating inflammation, cardiovascular functions, and angiogenesis. EETs were shown to be especially potent promoters of tissue regeneration. Considering their anti-inflammatory and anti-catabolic potential, we investigated whether EETs can influence IVD degeneration. We found that 14,15-EET protected rat nucleus pulposus (NP) cells against death induced by treatment with H2O2and TNF-α in vitro. At the molecular level, 14,15-EET significantly inhibited the NF-κB pathway, which plays essential roles in the degeneration and survival of NP cells. As a result, 14,15-EET efficiently prevented the matrix remodeling response of NP cells to TNF-α. Using a needle-punctured rat tail model, the influence of 14,15-EET on IVD degeneration in vivo was evaluated using radiographs, magnetic resonance images (MRI), and histological analysis. We observed that 14,15-EET prevented IVD degeneration. Our findings demonstrated that 14,15-EET can enhance the survival of NP cells and inhibit IVD degeneration. The EET pathway may be a novel therapeutic target against IVD degeneration.

One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of α7 nAChR in up-regulation of Aβ induced by gp120, METH and NT. Aβ release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of α7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of Aβ, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and Aβ in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that α7 nAChR may play an important role in neuropathology caused by gp120, METH and NT, which are the major pathogenic factors contributing to the pathogenesis of HAND.

Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model.

Previous studies at 21 °C and 5 °C suggest that in Swiss mice sustained energy intake (SusEI) and reproductive performance are constrained by the mammary capacity to produce milk. We aimed to establish if this constraint also applied at higher ambient temperature (30 °C). Female Swiss mice lactating at 30 °C had lower asymptotic food intake and weaned lighter litters than those at 21 °C. Resting metabolic rate, daily energy expenditure, milk energy output and suckling time were all lower at 30 °C. In a second experiment we gave mice at 30 °C either 6 or 9 pups to raise. Female performance was independent of litter size, indicating that it is probably not controlled by pup demands. In a third experiment we exposed only the mother, or only the offspring to the elevated temperature. In this case the performance of the mother was only reduced when she was exposed, and not when her pups were exposed, showing that the high temperature directly constrains female performance. These data suggest that at 30 °C SusEI and reproductive performance are likely constrained by the capacity of females to dissipate body heat, and not indirectly via pup demands. Constraints seem to change with ambient temperature in this strain of mouse.

DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1-) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.

The serine protease inhibitor clade E member 1 (SERPINE1) gene has been suggested to exert great influence on the development of sepsis. But there is little overlap in the results of association between SERPINE1 -675 4G/5G polymorphism and sepsis.To get a more precise estimation of this association, we conducted a meta-analysis with a relatively larger sample size including 1806 cases and 2239 controls. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between -675 4G/5G polymorphism and sepsis susceptibility. Subgroup analyses were conducted based on ethnicity and source of controls.The results showed that there was no association of the SERPINE1 polymorphism and sepsis susceptibility (5G5G vs 4G4G: OR = 0.87, CI = 0.75-1.03; 5G5G+4G5G vs 4G4G: OR = 0.93, CI = 0.84-1.02; 5G5G vs 4G4G+4G5G: OR = 0.96, CI = 0.83-1.11; 5G vs 4G: OR = 0.94, CI = 0.86-1.01; 4G5G vs 4G4G: OR = 0.90, CI = 0.80-1.01). Nor did any subgroup analysis indicate a significant association.In conclusion, -675 4G/5G polymorphism in the SERPINE1 gene may not be associated with the risk of sepsis.

Psoriasis is recently characterized by a specific microRNAs (miRNAs) expression profile, which guides the researchers' efforts to explore the therapeutic targets and objective biomarkers that reflect the diagnosis and disease activity in clinical use for psoriasis.The paper presents a state-of-the-art review of expression and function of miRNAs in psoriasis along with its clinical implications.We analyzed all literature searched by keywords "microRNA" and "psoriasis" in PubMed (Medline) from inception up to July 2015, and the references in the literature searched were also considered.Relevant literature was chosen according to the objective of this review. Relevant literature was searched by 3 independent investigators, and experts in the field of miRNAs and psoriasis were involved in analyzing process.We included any study in which role of miRNAs in psoriasis was examined in relation to disease pathogenesis, diagnosis, and treatment.The specific miRNAs profile has been identified from human psoriatic skin, blood, and hair samples. It is found that genetic polymorphisms related to some of specific miRNAs, miR-146a for example, are associated with psoriasis susceptibility. Key roles of several unique miRNAs, such as miR-203 and miR-125b, in inflammatory responses and immune dysfunction, as well as hyperproliferative disorders of psoriatic lesions have been revealed. Moreover, circulating miRNAs detected from blood samples have a potential of clinic application to be the biomarkers of diagnosis, prognosis, and treatment responses. Additionally, a new layer of regulatory mechanisms mediated by miRNAs is to some extent revealed in pathogenesis of psoriasis.The dramatically altered mRNA expression profiles are displayed in psoriasis, and some of these may become disease markers and therapeutic targets. Herein, this work underscores the potential importance of miRNAs to diagnosis, prognosis, and treatment of psoriasis. However, further study in this field is worth doing in the future, as the exact roles of miRNAs in psoriasis have not been fully elucidated.Systematic review registration number is not registered.