Asp-tRNAAsn/Glu-tRNAGln amidotransferase A subunit-like amidase mediates the degradation of insecticide flonicamid by Variovorax boronicumulans CGMCC 4969.

The main metabolic product of the pyridinecarboxamide insecticide flonicamid, N-(4-trifluoromethylnicotinyl)glycinamide (TFNG-AM), has been shown to have very high mobility in soil, leading to its accumulation in the environment. Catabolic pathways of flonicamid have been widely reported, but few studies have focused on the metabolism of TFNG-AM. Here, the rapid transformation of TFNG-AM and production of the corresponding acid product N-(4-trifluoromethylnicotinoyl) glycine (TFNG) by the plant growth-promoting bacterium Variovorax boronicumulans CGMCC 4969 were investigated. With TFNG-AM at an initial concentration of 0.86 mmol/L, 90.70 % was transformed by V. boronicumulans CGMCC 4969 resting cells within 20 d, with a degradation half-life of 4.82 d. A novel amidase that potentially mediated this transformation process, called AmiD, was identified by bioinformatic analyses. The gene encoding amiD was cloned and expressed recombinantly in Escherichia coli, and the enzyme AmiD was characterized. Key amino acid residue Val154, which is associated with the catalytic activity and substrate specificity of signature family amidases, was identified for the first time by homology modeling, structural alignment, and site-directed mutagenesis analyses. When compared to wild-type recombinant AmiD, the mutant AmiD V154G demonstrated a 3.08-fold increase in activity toward TFNG-AM. The activity of AmiD V154G was greatly increased toward aromatic L-phenylalanine amides, heterocyclic TFNG-AM and IAM, and aliphatic asparagine, whereas it was dramatically lowered toward benzamide, phenylacetamide, nicotinamide, acetamide, acrylamide, and hexanamid. Quantitative PCR analysis revealed that AmiD may be a substrate-inducible enzyme in V. boronicumulans CGMCC 4969. The mechanism of transcriptional regulation of AmiD by a member of the AraC family of regulators encoded upstream of the amiD gene was preliminarily investigated. This study deepens our understanding of the mechanisms of metabolism of toxic amides in the environment, providing new ideas for microbial bioremediation.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Long-term fasting induced basal thermogenesis flexibility in female Japanese quails.

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.

Research Progress of Electroplated Nanotwinned Copper in Microelectronic Packaging.

Copper is the most common interconnecting material in the field of microelectronic packaging, which is widely used in advanced electronic packaging technologies. However, with the trend of the miniaturization of electronic devices, the dimensions of interconnectors have decreased from hundreds of microns to tens of or even several microns, which has brought serious reliability issues. As a result, nanotwinned copper (nt-Cu) has been proposed as a potential candidate material and is being certified progressively. Firstly, the physical properties of nt-Cu have been widely studied. Notably, the higher thermal stability and oxidation resistance of the (111) texture causes nt-Cu to maintain excellent physical properties under high-temperature serving conditions. Secondly, recent works on the electrolyte and electroplating processes of nt-Cu on wafer substrates are summarized, focusing on how to reduce the thickness of the transition layer, improve the twin density, and achieve complicated pattern filling. Thirdly, nt-Cu can effectively eliminate Kirkendall voids when it serves as UBM or a CuP. Additionally, the high (111) texture can control the preferred orientation of interfacial intermetallic compounds (IMCs) at the Cu-Sn interface, which should be helpful to improve the reliability of solder joints. nt-Cu has superior electromigration resistance and antithermal cycling ability compared to ordinary copper RDLs and TSVs. Above all, nt-Cu has attracted much attention in the field of microelectronic packaging in recent years. The preparation-performance-reliability interrelationship of nt-Cu is summarized and displayed in this paper, which provides a solid theoretical basis for its practical applications.

Biodegradation of sulfoxaflor and photolysis of sulfoxaflor by ultraviolet radiation.

Sulfoxaflor (SUL, [N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl] ethyl]-λ4-sulfanylidene] cyanamide]) is a widely used systemic insecticide, and its residue has frequently been detected in the environment, posing a potential threat to the environment. In this study, Pseudaminobacter salicylatoxidans CGMCC 1.17248 rapidly converted SUL into X11719474 via a hydration pathway mediated by two nitrile hydratases (AnhA and AnhB). Extensive (96.4%) degradation of 0.83 mmol/L SUL was achieved by P. salicylatoxidans CGMCC 1.17248 resting cells within 30 min (half-life of SUL 6.4 min). Cell immobilization by entrapment into calcium alginate remediated 82.8% of the SUL in 90 min, and almost no SUL was observed in surface water after incubation for 3 h. P. salicylatoxidans NHases AnhA and AnhB both hydrolyzed SUL to X11719474, although AnhA exhibited much better catalytic performance. The genome sequence of P. salicylatoxidans CGMCC 1.17248 revealed that this strain could efficiently eliminate nitrile-containing insecticides and adapt to harsh environments. We firstly found that UV irradiation transforms SUL to the derivatives X11719474 and X11721061, and the potential reaction pathways were proposed. These results further deepen our understanding of the mechanisms of SUL degradation as well as the environmental fate of SUL.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.

Breast cancer-related lymphoedema and resistance exercise: An evidence-based review of guidelines, consensus statements and systematic reviews.

AIMS AND OBJECTIVES: Breast cancer-related lymphoedema (BCRL) is a side effect of cancer treatment and can be alleviated by resistance exercise. This systematic, evidence-based review examined the existing best evidence on resistance exercise for BCRL to accurately describe the current status of the field and offer recommendations for clinicians. METHODS: This review adheres to the PRISMA guidelines. Clinical practice guidelines, consensus documents, systematic reviews and other related evidence-based resources about resistance exercise for BCRL were retrieved through the English databases and guideline websites. The publication data limit was set to December 2020. The following search terms were used: 'breast cancer/breast neoplasm/breast carcinoma/breast tumor/breast malignancy, lymphedema/swelling/edema/lymphoedema, resistance/weight/strength training, best practice/clinical practice/guideline/consensus documents'. The quality of the included studies was evaluated by two authors independently using AGREE II and AMSTAR II tools. Evidence-based recommendations on resistance exercise relevant for BCRL were synthesised and categorised. RESULTS: Twenty two articles (seven guidelines, four consensus documents and eleven systematic reviews) were included. The overall quality of the eleven eligible guidelines and consensus documents was moderate to high according to the AGREE II criteria. The quality of the eleven systematic reviews was critically low to high according to the AMSTAR criteria. Six clinical topics involving 43 recommendations were identified. Recommendations were categorised by safety of resistance training, effectiveness of resistance training, evaluation prior to resistance exercise, resistance exercise prescription, resistance training outcome index and points for attention. CONCLUSIONS: This study summarises 43 recommendations for resistance training for BCRL and provides guidance for clinicians. Based on randomised trials and systematic reviews published in recent years, there is an urgent need to update the guidelines and consensus documents in terms of topics, for example effectiveness of resistance training and resistance training outcome index.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Nitroreduction of imidacloprid by the actinomycete Gordonia alkanivorans and the stability and acute toxicity of the nitroso metabolite.

The insecticide imidacloprid (IMI), which is used worldwide, pollutes environments and has significant ecotoxicological effects. Microbial metabolism and photolysis are the major pathways of IMI degradation in natural environments. Several studies have reported that the metabolites of IMI nitroreduction are more toxic to some insects and mammals than IMI itself. Thus, environmental degradation of IMI may enhance the ecotoxicity of IMI and have adverse effects on non-target organisms. Here, we report that an actinomycete-Gordonia alkanivorans CGMCC 21704-transforms IMI to a nitroreduction metabolite, nitroso IMI. Resting cells of G. alkanivorans at OD600 nm = 10 transformed 95.7% of 200 mg L-1 IMI to nitroso IMI in 4 d. Nitroso IMI was stable at pH 4-9. However, it rapidly degraded under sunlight via multiple oxidation, dehalogenation, and oxidative cleavage reactions to form 10 derivatives; the half-life of nitroso IMI in photolysis was 0.41 h, compared with 6.19 h for IMI. Acute toxicity studies showed that the half maximal effective concentration (EC50) values of IMI, nitroso IMI, and its photolytic metabolites toward the planktonic crustacean Daphnia magna for immobilization (exposed to the test compounds for 48 h) were 17.70, 9.38, 8.44 mg L-1, respectively. The half-life of nitroso IMI in various soils was also examined. The present study reveals that microbial nitroreduction accelerates IMI degradation and the nitroso IMI is easily decomposed by sunlight and in soil. However, nitroso IMI and its photolytic products have higher toxicity toward D. magna than the parent compound IMI, and therefore increase the ecotoxicity of IMI.

A fecal-based test for the detection of advanced adenoma and colorectal cancer: a case-control and screening cohort study.

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Screening is a confirmed way to reduce the incidence and mortality rates of CRC. This study aimed to identify a fecal-based, noninvasive, and accurate method for detection of colorectal cancer (CRC) and advanced adenoma (AA). METHODS: Through detection in tissue (n = 96) and fecal samples (n = 88) and tested in an independent group of fecal samples (n = 294), the methylated DNA marker ITGA4 and bacterial markers Fusobacterium nucleatum (Fn) and Pepetostreptococcusanaerobius (Pa) were identified from the candidate biomarkers for CRC and AA detection. A prediction score (pd-score) was constructed using the selected markers and fecal immunochemical test (FIT) for distinguishing AA and CRC from healthy subjects by logistic regression method. The diagnostic performance of the pd-score was compared with FIT and validated in the external validation cohort (n = 117) and in a large CRC screening cohort. RESULTS: The pd-score accurately identified AA and CRC from healthy subjects with an area under the curve (AUC) of 0.958, at a specificity of 91.37%; the pd-score showed sensitivities of 95.38% for CRC and 70.83% for AA, respectively. In the external validation cohort, the sensitivities of the pd-score for CRC and AA detection were 94.03% and 80.00%, respectively. When applied in screening, the pd-score identified 100% (11/11) of CRC and 70.83% (17/24) of AA in participants with both colonoscopy results and qualified fecal samples, showing an improvement by 41.19% compared to FIT. CONCLUSIONS: The current study developed a noninvasive and well-validated approach for AA and CRC detection, which could be applied widely as a diagnostic and screening test.

Biodegradation of flonicamid by Ensifer adhaerens CGMCC 6315 and enzymatic characterization of the nitrile hydratases involved.

BACKGROUND: Flonicamid (N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a new type of pyridinamide insecticide that regulates insect growth. Because of its wide application in agricultural production and high solubility in water, it poses potential risks to aquatic environments and food chain. RESULTS: In the present study, Ensifer adhaerens CGMCC 6315 was shown to efficiently transform FLO into N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) via a hydration pathway mediated by two nitrile hydratases, PnhA and CnhA. In pure culture, resting cells of E. adhaerens CGMCC 6315 degraded 92% of 0.87 mmol/L FLO within 24 h at 30 °C (half-life 7.4 h). Both free and immobilized (by gel beads, using calcium alginate as a carrier) E. adhaerens CGMCC 6315 cells effectively degraded FLO in surface water. PnhA has, to our knowledge, the highest reported degradation activity toward FLO, Vmax = 88.7 U/mg (Km = 2.96 mmol/L). Addition of copper ions could increase the enzyme activity of CnhA toward FLO by 4.2-fold. Structural homology modeling indicated that residue ß-Glu56 may be important for the observed significant difference in enzyme activity between PnhA and CnhA. CONCLUSIONS: Application of E. adhaerens may be a good strategy for bioremediation of FLO in surface water. This work furthers our understanding of the enzymatic mechanisms of biodegradation of nitrile-containing insecticides and provides effective transformation strategies for microbial remediation of FLO contamination.

Biodegradation of the pyridinecarboxamide insecticide flonicamid by Microvirga flocculans and characterization of two novel amidases involved.

Flonicamid (N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a new type of pyridinecarboxamide insecticide that exhibits particularly good efficacy in pest control. However, the extensive use of FLO in agricultural production poses environmental risks. Hence, its environmental behavior and degradation mechanism have received increasing attention. Microvirga flocculans CGMCC 1.16731 rapidly degrades FLO to produce the intermediate N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) and the end acid metabolite 4-(trifluoromethyl) nicotinol glycine (TFNG). This bioconversion is mediated by the nitrile hydratase/amidase system; however, the amidase that is responsible for the conversion of TFNG-AM to TFNG has not yet been reported. Here, gene cloning, overexpression in Escherichia coli and characterization of pure enzymes showed that two amidases-AmiA and AmiB-hydrolyzed TFNG-AM to TFNG. AmiA and AmiB showed only 20-30% identity to experimentally characterized amidase signature family members, and represent novel amidases. Compared with AmiA, AmiB was more sensitive to silver and copper ions but more resistant to organic solvents. Both enzymes demonstrated good pH tolerance and exhibited broad amide substrate specificity. Homology modeling suggested that residues Asp191 and Ser195 may strongly affect the catalytic activity of AmiA and AmiB, respectively. The present study furthers our understanding of the enzymatic mechanisms of biodegradation of nitrile-containing insecticides and may aid in the development of a bioremediation agent for FLO.

Chromium (VI) promotes EMT by regulating FLNA in BLCA.

Hexavalent chromium (Cr (VI)), which is a recognized human carcinogen, is widely used in industrial production of raw materials. Evidence verifies that environmental contaminants in the urine can induce malignant transformation in the urinary bladder tract, and our data indicate that Cr (VI) could promote the proliferation and migration and inhibit the apoptosis of bladder cancer (BLCA) cells. However, the molecular mechanism remains ambiguous. We find that Filamin A (FLNA) is overexpressed in BLCA, and Cr (VI) promotes epithelial-to-mesenchymal transition by regulating FLNA in BLCA. Thus, inhibiting the expression of FLNA may be a prospective method for limiting the BLCA progression caused by Cr (VI) exposure.

CD47 Deficiency in Mice Exacerbates Chronic Fatty Diet-Induced Steatohepatitis Through Its Role in Regulating Hepatic Inflammation and Lipid Metabolism.

Inflammation is one of the hallmarks of non-alcoholic steatohepatitis. CD47 is a widely expressed transmembrane protein that signals through inhibitory receptor signal regulatory protein α (SIRPα) to inhibit macrophage activation and phagocytosis. In this study, we sought to investigate the role of CD47 in hepatosteatosis and fibrosis induced by a chronic high-fat diet (HFD), by comparing disease development in wild-type (WT) and CD47KO mice fed HFD for 40 weeks. The HFD induced remarkably more severe hepatic steatosis and fibrosis but less body weight gain and less subcutaneous fat accumulation in CD47KO mice compared to WT mice. Liver tissues from HFD-fed CD47KO mice exhibited enhanced inflammation characterized by increased proinflammatory cytokine production and increased nuclear factor-κB (NF-κB) activation compared to similarly fed WT mice. Although higher expression of apolipoproteins was observed in CD47KO mice compared to WT mice under a low-fat diet (LFD), HFD-fed WT and CD47KO mice showed comparably prominent downregulation of these apolipoprotein genes, suggesting that the marked difference observed in lipid accumulation and hepatosteatosis between these mice cannot be explained by changes in apolipoproteins. Like apolipoproteins, sirtuin 1 (SIRT1) and peroxisome proliferator activated receptor alpha (PPARα), which are involved in regulation of both lipid metabolism and inflammation, were more highly expressed in CD47KO than WT mice under LFD but more severely suppressed in CD47KO than in WT mice under HFD. Taken together, our results indicate that CD47 plays a significant role in the pathogenesis of HFD-induced hepatosteatosis and fibrosis through its role in regulation of inflammation and lipid metabolism.

Long-term exposure to urban air pollution and lung cancer mortality: A 12-year cohort study in Northern China.

Cohort evidence that links long-term exposures to air pollution and mortality comes largely from the United States and European countries. We investigated the relationship between long-term exposures to particulate matter <10µm in diameter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) and mortality of lung cancer in Northern China. A cohort of 39,054 participants were followed during 1998-2009. Annual average concentrations for PM10, NO2, and SO2 were determined based on data collected from central monitoring stations. Lung cancer deaths (n=140) were obtained from death certificates, and hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusting for age, gender, BMI, education, marital status, smoking status, passive smoking, occupation, alcohol consumption, etc. Each 10mg/m(3) increase in PM10 concentrations was associated with a 3.4%-6.0% increase in lung cancer mortality in the time-varying exposure model and a 4.0%-13.6% increase in the baseline exposure model. In multi-pollutant models, the magnitude of associations was attenuated, most strongly for PM10. The association was different in men and women, also varying across age categories and different smoking status. Substantial differences exist in the risk estimates for participants based on assignment method for air pollution exposure.

Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer.

Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

Novel anti-melanoma treatment: focus on immunotherapy.

Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

Pouch size influences clinical outcome of pouch construction after total gastrectomy: a meta-analysis.

AIM: To assess the clinical significance of pouch size in total gastrectomy for gastric malignancies. METHODS: We manually searched the English-language literature in PubMed, Cochrane Library, Web of Science and BIOSIS Previews up to October 31, 2013. Only randomized control trials comparing small pouch with large pouch in gastric reconstruction after total gastrectomy were eligible for inclusion. Two reviewers independently carried out the literature search, study selection, data extraction and quality assessment of included publications. Standard mean difference (SMD) or relative risk (RR) and corresponding 95%CI were calculated as summary measures of effects. RESULTS: Five RCTs published between 1996 and 2011 comparing small pouch formation with large pouch formation after total gastrectomy were included. Eating capacity per meal in patients with a small pouch was significantly higher than that in patients with a large pouch (SMD = 0.85, 95%CI: 0.25-1.44, I(2) = 0, P = 0.792), and the operative time spent in the small pouch group was significantly longer than that in the large pouch group [SMD = -3.87, 95%CI: -7.68-(-0.09), I (2) = 95.6%, P = 0]. There were no significant differences in body weight at 3 mo (SMD = 1.45, 95%CI: -4.24-7.15, I(2) = 97.7%, P = 0) or 12 mo (SMD = -1.34, 95%CI: -3.67-0.99, I(2) = 94.2%, P = 0) after gastrectomy, and no significant improvement of post-gastrectomy symptoms (heartburn, RR = 0.39, 95%CI: 0.12-1.29, I(2) = 0, P = 0.386; dysphagia, RR = 0.86, 95%CI: 0.58-1.27, I(2) = 0, P = 0.435; and vomiting, RR = 0.5, 95%CI: 0.15-1.62, I(2) = 0, P = 0.981) between the two groups. CONCLUSION: Small pouch can significantly improve the eating capacity per meal after surgery, and may improve the post-gastrectomy symptoms, including heartburn, dysphagia and vomiting.