Genome comparison of long-circulating field CnmeGV isolates from the same region.

Cnaphalocrocis medinalis granulovirus (CnmeGV), belonging to Betabaculovirus cnamedinalis, can infect the rice pest, the rice leaf roller. In 1979, a CnmeGV isolate, CnmeGV-EP, was collected from Enping County, China. In 2014, we collected another CnmeGV isolate, CnmeGV-EPDH3, at the same location and obtained the complete virus genome sequence using Illumina and ONT sequencing technologies. By combining these two virus isolates, we updated the genome annotation of CnmeGV and conducted an in-depth analysis of its genome features. CnmeGV genome contains abundant tandem repeat sequences, and the repeating units in the homologous regions (hrs) exhibit overlapping and nested patterns. The genetic variations within EPDH3 population show the high stability of CnmeGV genome, and tandem repeats are the only region of high genetic variation in CnmeGV genome replication. Some defective viral genomes formed by recombination were found within the population. Comparison analysis of the two virus isolates collected from Enping showed that the proteins encoded by the CnmeGV-specific genes were less conserved relative to the baculovirus core genes. At the genomic level, there are a large number of SNPs and InDels between the two virus isolates, especially in and around the bro genes and hrs. Additionally, we discovered that CnmeGV acquired a segment of non-ORF sequence from its host, which does not provide any new proteins but rather serves as redundant genetic material integrated into the viral genome. Furthermore, we observed that the host's transposon piggyBac has inserted into some virus genes. Together, dsDNA viruses could acquire non-coding genetic material from their hosts to expand the size of their genomes. These findings provide new insights into the evolution of dsDNA viruses.

c-Jun targets miR-451a to regulate HQ-induced inhibition of erythroid differentiation via the BATF/SETD5/ARHGEF3 axis.

Benzene, a widely used industrial chemical, has been clarified to cause hematotoxicity. Our previous study suggested that miR-451a may play a role in benzene-induced impairment of erythroid differentiation. However, the mechanism underlying remains unclear. In this study, we explored the role of miR-451a and its underlying mechanisms in hydroquinone (HQ)-induced suppression of erythroid differentiation in K562 cells. 0, 1.0, 2.5, 5.0, 10.0, and 50 µM HQ treatment of K562 cells resulted in a dose-dependent inhibition of erythroid differentiation, as well as the expression of miR-451a. Bioinformatics analysis was conducted to predict potential target genes of miR-451a and dual-luciferase reporter assays confirmed that miR-451a can directly bind to the 3'-UTR regions of BATF, SETD5, and ARHGEF3 mRNAs. We further demonstrated that over-expression or down-regulation of miR-451a altered the expression of BATF, SETD5, and ARHGEF3, and also modified erythroid differentiation. In addition, BATF, SETD5, and ARHGEF3 were verified to play a role in HQ-induced inhibition of erythroid differentiation in this study. Knockdown of SETD5 and ARHGEF3 reversed HQ-induced suppression of erythroid differentiation while knockdown of BATF had the opposite effect. On the other hand, we also identified c-Jun as a potential transcriptional regulator of miR-451a. Forced expression of c-Jun increased miR-451a expression and reversed the inhibition of erythroid differentiation induced by HQ, whereas knockdown of c-Jun had the opposite effect. And the binding site of c-Jun and miR-451a was verified by dual-luciferase reporter assay. Collectively, our findings indicate that miR-451a and its downstream targets BATF, SETD5, and ARHGEF3 are involved in HQ-induced erythroid differentiation disorder, and c-Jun regulates miR-451a as a transcriptional regulator in this process.

8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults.

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI - 0.658 ~ - 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

Empirical analysis of lead neurotoxicity mode of action and its application in health risk assessment.

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.

Co-exposure of petrochemical workers to noise and mixture of benzene, toluene, ethylbenzene, xylene, and styrene: Impact on mild renal impairment and interaction.

Epidemiological evidence concerning effects of simultaneous exposure to noise and benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) on renal function remains uncertain. In 2020, a cross-sectional study was conducted among 1160 petrochemical workers in southern China to investigate effects of their co-exposure on estimated glomerular filtration rate (eGFR) and mild renal impairment (MRI). Noise levels were assessed using cumulative noise exposure (CNE). Urinary biomarkers for BTEXS were quantified. We found the majority of workers had exposure levels to noise and BTEXS below China's occupational exposure limits. CNE, trans, trans-muconic acid (tt-MA), and the sum of mandelic acid and phenylglyoxylic acid (PGMA) were linearly associated with decreased eGFR and increased MRI risk. We observed U-shaped associations for both N-acetyl-S-phenyl-L-cysteine (SPMA) and o-methylhippuric acid (2-MHA) with MRI. In further assessing the joint effect of BTEXS (ß, -0.164 [95% CI, -0.296 to -0.033]) per quartile increase in all BTEXS metabolites on eGFR using quantile g-computation models, we found SPMA, tt-MA, 2-MHA, and PGMA played pivotal roles. Additionally, the risk of MRI associated with tt-MA was more pronounced in workers with lower CNE levels (P = 0.004). Multiplicative interaction analysis revealed antagonisms of CNE and PGMA on MRI risk (P = 0.034). Thus, our findings reveal negative dose-effect associations between noise and BTEXS mixture exposure and renal function in petrochemical workers. With the exception of toluene, benzene, xylene, ethylbenzene, and styrene are all concerning pollutants for renal dysfunction. Effects of benzene, ethylbenzene, and styrene exposure on renal dysfunction were more pronounced in workers with lower CNE.

Alterations of the gut microbiota in type 2 diabetics with or without subclinical hypothyroidism.

Background: Diabetes and thyroid dysfunction are two closely related endocrine diseases. Increasing evidences show that gut microbiota plays an important role in both glucose metabolism and thyroid homeostasis. Meanwhile, copy number variation (CNV) of host salivary α-amylase gene (AMY1) has been shown to correlate with glucose homeostasis. Hence, we aim to characterize the gut microbiota and CNV of AMY1 in type 2 diabetes (T2D) patients with or without subclinical hypothyroidism (SCH). Methods: High-throughput sequencing was used to analyze the gut microbiota of euthyroid T2D patients, T2D patients with SCH and healthy controls. Highly sensitive droplet digital PCR was used to measure AMY1 CN. Results: Our results revealed that T2D patients have lower gut microbial diversity, no matter with or without SCH. The characteristic taxa of T2D patients were Coriobacteriales, Coriobacteriaceae, Peptostreptococcaceae, Pseudomonadaceae, Collinsella, Pseudomonas and Romboutsia. Meanwhile, Escherichia/Shigella, Lactobacillus_Oris, Parabacteroides Distasonis_ATCC_8503, Acetanaerobacterium, Lactonifactor, uncultured bacterium of Acetanaerobacterium were enriched in T2D patients with SCH. Moreover, serum levels of free triiodothyronine (FT3) and free thyroxine (FT4) in T2D patients were both negatively correlated with richness of gut microbiota. A number of specific taxa were also associated with clinical parameters at the phylum and genus level. In contrast, no correlation was found between AMY1 CN and T2D or T2D_SCH. Conclusion: This study identified characteristic bacterial taxa in gut microbiota of T2D patients with or without SCH, as well as the taxa associated with clinical indices in T2D patients. These results might be exploited in the prevention, diagnosis and treatment of endocrine disorders in the future.

Long-read genome assemblies reveal a cis-regulatory landscape associated with phenotypic divergence in two sister Siniperca fish species.

Due to the difficulty in accurately identifying structural variants (SVs) across genomes, their impact on cis-regulatory divergence of closely related species, especially fish, remains to be explored. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remains poorly understood. Siniperca chuatsi and S. scherzeri are closely related but divergent in several phenotypic traits, making them an ideal model to study cis-regulatory evolution in sister species. Here, we generated chromosome-level genomes of S. chuatsi and S. scherzeri, with assembled genome sizes of 716.35 and 740.54 Mb, respectively. The evolutionary histories of S. chuatsi and S. scherzeri were studied by inferring dynamic changes in ancestral population sizes. To explore the genetic basis of adaptation in S. chuatsi and S. scherzeri, we performed gene family expansion and contraction analysis and identified positively selected genes (PSGs). To investigate the role of SVs in cis-regulatory divergence of closely related fish species, we identified high-quality SVs as well as divergent H3K27ac and H3K4me3 domains in the genomes of S. chuatsi and S. scherzeri. Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in phenotypic divergence between S. chuatsi and S. scherzeri. Additionally, divergent broad H3K4me3 domains were mostly associated with cancer-related genes in S. chuatsi and S. scherzeri and contributed to their phenotypic divergence.

Assessment of health risk and dose-effect of DNA oxidative damage for the thirty chemicals mixture of parabens, triclosan, benzophenones, and phthalate esters.

Humans are constantly exposed to parabens (PBs), triclosan (TCS), benzophenones (BPs), and phthalate esters (PAEs) due to the widespread existence of these chemicals in personal care products (PCPs), and the high frequency of usage for humans. Previous studies indicated each class of the above-mentioned chemicals can exhibit potential adverse effects on humans, in particular DNA oxidative damage. However, the health risk assessment of combined exposures to multiple PCPs is limited, especially the overall dose-effect of mixtures of these chemicals on DNA oxidative damage. In this study, we measured the urinary levels of 6 PBs, TCS, 8 BPs, 15 metabolites of PAEs (mono-PAEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from 299 adults simultaneously. PBs, TCS, BPs, and mono-PAEs were frequently detected in urinary samples with median concentrations of 52.888, 0.737, 1.305, and 141.381 ng/ml, suggesting a broad, low-level exposure among participants. Risk assessments indicated approximately 22% and 15% of participants suffered health risks (Hazard index >1) from exposure to TCS and PAEs. The relationship between 8-OHdG levels and chemical exposure was estimated by Bayesian kernel machine regression (BKMR) models. It indicated an overall positive correlation between the mixture of these chemicals and 8-OHdG, with methylparaben and mono-benzyl phthalate contributing the most to this association. Of note, sex-related differences were observed, in which exposure to PCPs led to higher health risks and more pronounced dose-effect on DNA damage in the female population. Our novel findings reveal the health risks of exposure to low-level PCPs mixtures and further point out the overall dose-response relationship between DNA oxidative damage and PCP mixtures.

Synergistic Catalysis of SnO2/Reduced Graphene Oxide for VO2+/VO2+ and V2+/V3+ Redox Reactions.

In spite of their low cost, high activity, and diversity, metal oxide catalysts have not been widely applied in vanadium redox reactions due to their poor conductivity and low surface area. Herein, SnO2/reduced graphene oxide (SnO2/rGO) composite was prepared by a sol-gel method followed by high-temperature carbonization. SnO2/rGO shows better electrochemical catalysis for both redox reactions of VO2+/VO2+ and V2+/V3+ couples as compared to SnO2 and graphene oxide. This is attributed to the fact that reduced graphene oxide is employed as carbon support featuring excellent conductivity and a large surface area, which offers fast electron transfer and a large reaction place towards vanadium redox reaction. Moreover, SnO2 has excellent electrochemical activity and wettability, which also boost the electrochemical kinetics of redox reaction. In brief, the electrochemical properties for vanadium redox reactions are boosted in terms of diffusion, charge transfer, and electron transport processes systematically. Next, SnO2/rGO can increase the energy storage performance of cells, including higher discharge electrolyte utilization and lower electrochemical polarization. At 150 mA cm-2, the energy efficiency of a modified cell is 69.8%, which is increased by 5.7% compared with a pristine one. This work provides a promising method to develop composite catalysts of carbon materials and metal oxide for vanadium redox reactions.

Long non-coding RNA TDRG1 facilitates cell proliferation, migration and invasion in breast cancer via targeting miR-214-5p/CLIC4 axis.

Accumulated studies have revealed the critical role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of various cancers. LncRNA TDRG1 has been reported to exhibit oncogenic potential in some cancers. However, its underlying mechanism regulating breast cancer (BC) remains obscure. QRT-PCR was used to measure the relative expression of mRNAs, and western blot was used to detect protein expression levels. CCK8 and CFSE assays were utilized to testify cell proliferation ability. Flow cytometry assay was used for cell apoptosis ability investigation. Transwell and tube formation assays were implemented to test cell migrating and invasive abilities. Relevant mechanism experiments were implemented to determine the molecular mechanism. TDRG1 was remarkably overexpressed in BC cell lines. TDRG1 knockdown suppressed cell proliferation, migration and invasion, but enhanced BC cell apoptosis. Mechanistically, TDRG1 acted as a miR-214-5p sponge to up-regulate CLIC4 expression. MiR-214-5p inhibition or CLIC4 overexpression could revive the tumor-suppressing effects induced by TDRG1 knockdown. TDRG1 promoted cell proliferation, migration, and invasion in BC, suggesting that TDRG1 could promisingly be a therapeutic target for BC.

miR-520h Stimulates Drug Resistance to Paclitaxel by Targeting the OTUD3-PTEN Axis in Breast Cancer.

MicroRNAs (miRNAs) have been identified as negative posttranscriptional regulators of target genes and are involved directly in the pathological processes of tumors, including drug resistance. However, the exact function of miR-520h in breast cancer remains poorly understood. The aim of this study was to investigate the molecular mechanisms of miR-520h in paclitaxel resistance in the MCF-7 breast cancer cell line. Ectopic expression of miR-520h could promote the proliferation of breast cancer cells and inhibit paclitaxel-induced cell apoptosis. Inhibiting the expression of miR-520h could enhance the sensitivity to paclitaxel in paclitaxel-resistant MCF-7/Taxol cells. Furthermore, luciferase reporter assays showed that OTUD3 was a direct target of miR-520h. OTUD3 plays a necessary role in the paclitaxel resistance effect of miR-520h, and cotreatment with a miR-520h inhibitor and OTUD3 overexpression significantly enhanced MCF-7 cell sensitivity to paclitaxel. Moreover, miR-520h substantially inhibited the protein expression of PTEN via OTUD3 and subsequently affected downstream p-AKT pathway activity. In a clinical study, we also found that high miR-520h expression was associated with more aggressive pathological characteristic and poor prognosis. Therefore, our findings showed that miR-520h targeted the OTUD3-PTEN axis to drive paclitaxel resistance, and this miR might be an important potential target for breast cancer treatment.

Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells.

BACKGROUND: P53 pathway inactivation plays an important role in the process of breast cancer tumorigenesis. Post-translational protein modification abnormalities have been confirmed to be an important mechanism underlying inactivation of p53. Numerous deubiquitinating enzymes are aberrantly expressed in breast cancer, and a few deubiquitination enzymes can deubiquitinate and stabilize p53. Here, we report that ovarian tumor (OTU) deubiquitinase 3 (OTUD3) is a deubiquitylase of p53 in breast carcinoma (BC). METHODS: Correlations between the mRNA expression levels of OTUD3, TP53 and PTEN and the prognosis of BC were assessed with the Kaplan-Meier Plotter tool. OTUD3 protein expression in 80 pairs of specimens in our cohort was examined by immunohistochemistry and western blotting. The relationship among OTUD3, p53, and p21 proteins was analyzed. Half-life analysis and ubiquitylation assay were performed to elucidate the molecular mechanism by which OTUD3 stabilizes p53. The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments. MTS assay for proliferation detection, detection of apoptosis induced by cisplatin and colony formation assay were employed to investigate the functional effects of OTUD3 on breast cancer cells. RESULTS: OTUD3 downregulation is correlated with a poor prognosis in BC patients. OTUD3 expression is decreased in breast cancer tissues and not associated with the histological grade. OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs. Reduced OTUD3 expression accompanied by decreased p53 abundance is correlated with human breast cancer progression. Ectopic expression of wild-type OTUD3, but not its catalytically inactive mutant, stabilizes and activates p53. Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region. Finally, OTUD3 protects p53 from murine double minute 2 (Mdm2)-mediated ubiquitination and degradation, enabling the deubiquitination of p53 in BC cells. CONCLUSIONS: In summary, we found that OTUD3 may be a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signaling axis may play a critical role in tumor suppression.

Prognostic Significance of Metastatic Lymph Nodes Ratio (MLNR) Combined with Protein-Tyrosine Phosphatase H1 (PTPH1) Expression in Operable Breast Invasive Ductal Carcinoma.

PURPOSE: The metastatic lymph node ratio (MLNR) is one of the most important factors in prognostic analysis of breast cancer. The objective of this study was to determine if MLNR combined with protein-tyrosine phosphatase H1 (PTPH1) pathological expression can be used to predict the prognosis of patients with breast invasive ductal carcinoma (IDC) better than one factor only. PATIENTS AND METHODS: A total of 136 patients with invasive ductal carcinoma (IDC) of breast who underwent modified radical mastectomy and were treated with chemotherapy after operation at Qilu Hospital of Shandong University from December 2008 to October 2011 were included. PTPH1 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PTPH1 expression. A prognostic factor for disease-free survival (DFS) was identified by univariate and multivariate analyses. ROC analysis was used to evaluate the performance of single factors and combined feature. RESULTS: One hundred and thirty-six patients were included in the analysis. By cut-point survival analysis, MLNR cut-off was designed as 0.2. On multivariate analysis, a MLNR>0.2 was associated with a worse DFS (HR=2.581, 95% CI=1.303-5.113, P=0.007). PTPH1 overexpression is correlated with a better DFS (HR=0.391, 95% CI=0.162-0.945, P=0.037). In addition, MLNR and PTPH1 combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve=0.795 [95% CI=0.694-0.896], P<0.001). CONCLUSION: These findings indicate that both PTPH1 and MLNR are accurate independent prognostic parameters in patients with IDC of the breast. Better information on IDC prognosis could be obtained from the combined feature.

The Novel Transcription Factor CREB3L4 Contributes to the Progression of Human Breast Carcinoma.

Breast carcinoma(BC)is the most common cancer type among females globally. Understanding the molecular pathways that trigger the development of BC is crucial for both prevention and treatment. As such, the role of transcription factors (TFs) in the development of BC is a focal point in this field. CREB3s play a critical role in initiating the unfolded protein response (UPR); however, the role of CREB3 family members in breast cancer development remains largely unknown. Here, we mined the ONCOMINE database for the transcriptional data of CREB3s in patients with BC. Then, the regulatory functions of a novel TF, CREB3L4, were investigated. CREB3L4 knockdown in MDA-MB-231 and MCF-7 cells suppressed proliferation and promoted apoptosis and cell cycle arrest. ChIP assays confirmed that CREB3L4 can directly bind to the PCNA promoter region, suggesting that the PCNA protein may be functionally downstream of CREB3L4. Additionally, the expression level of CREB3L4 was assessed using our cohort. CREB3L4 is upregulated in breast cancer tissues and is significantly associated with histological grade and tumour size (P = 0.001 and P < 0.001, respectively). Furthermore, PCNA expression was upregulated in breast cancer tissues and positively correlated with CREB3L4. In summary, CREB3L4 may play an important role in the progression of human BC and may serve as a therapeutic target.

Application of porous biomass carbon materials in vanadium redox flow battery.

Porous nano biomass carbon was synthesized by one-step method using scaphium scaphigerum as carbon source and was employed as negative catalyst for vanadium redox flow battery. Potassium ferrate was used to realize synchronous etching, introducing oxygen-containing groups and graphitization of scaphium scaphigerum to obtain porous, oxygen-rich, high-graphization carbon materials (SS-K/Fe). Compared with traditional two-step method, one-step method has advantages of low-time requirement, high efficiency and no pollution. The prepared SS-K/Fe sample has abundant microporous structure, high degree of graphitization and many oxygen-containing groups. The electrochemical test results show that the prepared carbon-based materials exhibit superior electrocatalytic capability for V2+/V3+ redox reaction. The electrode process can be accelerated from three steps including ion diffusion, electrochemical reaction and electron transfer processes, which are due to the enhancement of wetting performance and electrical conductivity, and an increase of effective catalytic area. Compared with pristine cell, the SS-K/Fe modified cell can improve the energy efficiency by 6.2% at the current density of 50 mA cm-2. This method is expected to realize low cost, green and renewable porous carbon materials for future energy storage systems.

SHOC2 is associated with the survival of breast cancer cells and has prognostic value for patients with breast cancer.

SHOC2 leucine rich repeat scaffold protein (SHOC2) has been identified as a positive regulator of the Ras pathway; however, the function of SHOC2 in breast cancer has rarely been explored. The current study investigated the effects of SHOC2 on breast cancer cell growth and evaluated its prognostic value in patients with breast cancer. The effects of SHOC2 on MCF­7 and MDA­MB­231 breast cancer cells were studied using short hairpin RNA. In total, 120 pairs of formalin­fixed, paraffin­embedded breast cancer tissue specimens were compared to normal tissue using immunohistochemical staining. SHOC2 knockdown significantly inhibited MCF­7 and MDA­MB­231 breast cancer cell proliferation, and induced cell apoptosis and cell cycle arrest. Additionally, the RAS­MAPK/PI3K pathway was inhibited by SHOC2 knockdown. In a clinical study, the results revealed that high SHOC2 expression was associated with more aggressive clinical characteristics of breast cancer. Moreover, Kaplan­Meier and Cox regression analyses indicated that SHOC2 expression was an independent prognostic factor for survival, suggesting that increased SHOC2 expression predicted a worse overall survival. This indicated that SHOC2 knockdown could affect breast cancer cell survival, and SHOC2 upregulation may be associated with a poor prognosis in patients with breast cancer.

The association between gut microbiota composition and BMI in Chinese male college students, as analysed by next-generation sequencing.

Altered gut microbial ecology contributes to the development of metabolic diseases including obesity. However, studies based on different populations have generated conflicting results due to diet, environment, methodologies, etc. The aim of our study was to explore the association between gut microbiota and BMI in Chinese college students. The 16S next-generation sequencing (NGS) was used to test the gut microbiota of nine lean, nine overweight/obesity and ten normal-weight male college students. The differences in gut microbiota distribution among three groups were compared, and the relationship between the richness, diversity, composition of gut microbiota and BMI were analysed. The predominant phyla Bacteroidetes and Firmicutes were further confirmed by real-time PCR. Metagenomic biomarker discovery was conducted by linear discriminant analysis (LDA) effect size (LEfSe). NGS revealed that gut microbiota composition was different among three groups, but there was no difference in the abundance ratio of Firmicutes:Bacteroidetes. Several bacterial taxa were in linear relationship with BMI (positive relationship: uncultured bacterium (Bacteroides genus); negative relationship: Porphyromonadaceae, Acidaminococcaceae, Rikenellaceae, Desulfovibrionaceae, Blautia, Anaerotruncus, Parabacteroides, Alistipes). Moreover, gut microbiota diversity decreased with the increase in BMI. And LEfSe analysis indicated that Blautia, Anaerotruncus and its uncultured species were significantly enriched in the lean group (LDA score ≥ 3), Parasuterella and its uncultured species were significantly enriched in the overweight/obese groups (LDA score ≥ 3). In general, gut microbiota composition and microbial diversity were associated with BMI in Chinese male college students. Our results might enrich the understanding between gut microbiota and obesity.

Exogenous γ-Aminobutyric Acid Treatment That Contributes to Regulation of Malate Metabolism and Ethylene Synthesis in Apple Fruit during Storage.

Organic acid is an important indicator of fruit quality, and malate is the predominant organic acid in apple fruit. However, the regulation of malate metabolism in postharvest fruit is rarely reported. Here, we found that, compared with a control treatment, a 10 mM γ-aminobutyric acid (GABA) treatment remarkably delayed the loss of tiftratable acidity and malate and increased the succinate and oxalate contents in "Cripps Pink" fruit stored in polyethylene bags at room temperature. The higher malate levels in GABA-treated fruit were accompanied by higher activities of cytosolic nicotinamide adenine dinucleotide-dependent malate dehydrogenase (cyNAD-MDH) and phosphoenolpyruvate carboxylase (PEPC) but lower cytosolic NAD phosphate-dependent malic enzyme (cyNADP-ME) and phosphoenolpyruvate carboxykinase (PEPCK) activities than those seen in control fruit. Notably, ethylene production was significantly reduced by GABA treatment, paralleling the downregulation of MdACS, MdACO, and MdERF expression. Meanwhile, GABA treatment also enhanced the activity of the GABA shunt and promoted the accumulation of GABA. This study provides new insights into the regulation of malate metabolism and reports for the first time the possible interplay between GABA and ethylene signaling pathways in apple fruit during postharvest storage.

Correlation of expression of WWOX and JNK with clinicopathologic features in human breast carcinoma.

The aim of our study was to compare the expression levels of c-Jun N-terminal kinase (JNK) and WW domain-containing oxidoreductase (WWOX) in human breast carcinoma, to analyze the correlation between the expression of WWOX and JNK with the clinicopathologic features of human breast carcinoma, and to explore the potential mechanism of their antitumor effects. The mRNA and protein levels of WWOX and JNK in forty paired breast carcinoma tissues and the adjacent normal tissues were detected by real-time quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Protein expression was further confirmed by immunohistochemistry (IHC). The mRNA expression levels of both JNK and WWOX were downregulated in carcinoma tissues relative to those in the adjacent normal tissues, as determined by Western blot analysis and IHC (P<0.01). JNK expression was positively correlated with WWOX expression (r=0.47, P=0.002). Both WWOX and JNK play important roles in breast cancer. Therefore, the antitumor ability of WWOX and JNK could supply significant information for therapeutic strategy.

HPV Status and Its Correlation with BCL2, p21, p53, Rb, and Survivin Expression in Breast Cancer in a Chinese Population.

Despite recent evidence, the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. The correlations of HPV infection with the clinicopathological features of breast cancer and the expression of cell cycle/apoptosis-associated proteins have not been well elucidated. In this study, we sought to determine the prevalence of high-risk HPVs (HR-HPVs) infection and BCL2, p21, p53, Rb, and survivin expression in breast cancer patients and to investigate the relationship of HPV with these cancer-related proteins, in an attempt to clarify the potential mechanism of HPV in breast cancer pathogenesis. HPV presence in 81 fresh breast cancer tissues was determined by hybrid capture 2 (HC2) assay, and expression of BCL2, p21, p53, Rb, and survivin was detected by immunohistochemistry. Here we showed that fourteen (17.3%) patients were HR-HPV positive. HPV infection demonstrated no significant correlation with the clinicopathological characteristics of breast cancer. HPV-positive tumors showed significantly higher BCL2 and lower p53 expression than HPV-negative tumors. Expression of p21, Rb, and survivin was not associated with HPV status. Our results suggest a possible role of HR-HPV in breast cancer carcinogenesis, in which BCL2 and p53 may be involved.