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This study aims to establish an ELISA method with high specificity for the detection of antibodies against Mycoplasma hyopneumoniae. Firstly, we constructed a recombinant strain Escherichia coli BL21(DE3)-pET-32a(+)-mhp336 to express the recombinant protein Mhp336 and used the purified Mhp336 as the coating antigen. Then, we optimized the ELISA parameters, including antigen concentration, blocking buffer, blocking time, dilution of serum, incubation time with serum, secondary antibody dilution, secondary antibody incubation time, colorimetric reaction time, and cut-off value. Afterwards, reproducibility experiments were conducted, and the cross reactivity of Mhp366 with other antisera of porcine major pathogens and the maximum dilution ratios of the sera were determined. Finally, 226 porcine serum samples were detected using the method established in this study, a commercial ELISA kit for M. hyopneumoniae antibody detection, and a convalescent serum ELISA kit for M. hyopneumoniae antibody detection. The detection results of the three methods were compared to evaluate the sensitivity and specificity of the ELISA method established in this study. For this method, the optimal antigen concentration, blocking buffer, blocking time, dilution of serum, incubation time with serum, secondary antibody dilution, secondary antibody incubation time, and colorimetric reaction time were 0.05 µg/mL, PBS containing 2.5% skim milk, 1 h, 1:500, 0.5 h, 1:10 000, 1 h, and 5 min, respectively. Validation of the ELISA method based on Mhp336 showed a cut-off value of 0.332. The coefficients of variation of both intra-batch and inter-batch kits were below 7%. The detection results of porcine serum samples indicated that the method established in this study outperformed the commercial ELISA kit and the convalescent serum ELISA kit for M. hyopneumoniae antibody detection in terms of sensitivity and specificity. We successfully established an ELISA method for detecting the antibodies against M. hyopneumoniae based on Mhp336 protein. This method demonstrated high sensitivity and specificity, serving as a tool for the prevention of mycoplasmal pneumonia of swine in pig farms.
Subject(s)
Antibodies, Bacterial , Enzyme-Linked Immunosorbent Assay , Mycoplasma hyopneumoniae , Recombinant Proteins , Enzyme-Linked Immunosorbent Assay/methods , Mycoplasma hyopneumoniae/immunology , Animals , Swine , Recombinant Proteins/immunology , Recombinant Proteins/genetics , Antibodies, Bacterial/immunology , Antibodies, Bacterial/blood , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli/immunology , Pneumonia of Swine, Mycoplasmal/immunology , Pneumonia of Swine, Mycoplasmal/diagnosis , Pneumonia of Swine, Mycoplasmal/microbiology , Sensitivity and Specificity , Bacterial Proteins/immunology , Bacterial Proteins/geneticsABSTRACT
KEY MESSAGE: A major and stable QTL, QFn.sau-1B.2, which can explain 13.6% of the PVE in FN and has a positive effect on resistance in SGR, was mapped and validated. The falling number (FN) is considered one of the most important quality traits of wheat grain and is the most important quality evaluation index for wheat trade worldwide. The quantitative trait loci (QTLs) for FN were mapped in three years of experiments. 23, 30, and 58 QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. Among them, seven QTLs were considered stable. QFn.sau-1B.2, which was mapped to the 1BL chromosome, can explain 13.6% of the phenotypic variation on average and is considered a major and stable QTL for FN. This QTL was mapped in a 1 cM interval and is flanked by the markers AX-110409346 and AX-108743901. Epistatic analysis indicated that QFN.sau-1B.2 has a strong influence on FN through both additive and epistatic effects. The Kompetitive Allele-Specific PCR marker KASP-AX-108743901, which is closely linked to QFn.sau-1B.2, was designed. The genetic effect of QFn.sau-1B.2 on FN was successfully confirmed in Chuannong18 × T1208 and CN17 × CN11 populations. Moreover, the results of the additive effects of favorable alleles for FN showed that the QTLs for FN had significant effects not only on FN but also on the resistance to spike germination. Within the interval of QFn.sau-1B.2, 147 high-confidence genes were found. According to the gene annotation and the transcriptome data, four genes might be associated with FN. QFn.sau-1B.2 may provide a new resource for the high-quality breeding of wheat in the future.
Subject(s)
Quantitative Trait Loci , Triticum , Triticum/genetics , Chromosome Mapping , Plant Breeding , PhenotypeABSTRACT
Introduction: The mulberry industry has thrived in China for millennia, offering significant ecological and economic benefits. However, the prevalence of mulberry ring rot disease poses a serious threat to the quality and yield of mulberry leaves. Methods: In this study, we employed a combination of transcriptomic and metabolomic analyses to elucidate the changes occurring at the transcriptional and metabolic levels in Morus notabilis in response to this disease infestation. Key metabolites identified were further validated through in vitro inhibition experiments. Results: The findings revealed significant enrichment in Kyoto Encyclopedia of Genes and Genomes pathways, particularly those related to flavonoid biosynthesis. Notably, naringenin, kaempferol, and quercetin emerged as pivotal players in M. notabilis' defense mechanism against this disease pathogen. The upregulation of synthase genes, including chalcone synthase, flavanone-3-hydroxylase, and flavonol synthase, suggested their crucial roles as structural genes in this process. In vitro inhibition experiments demonstrated that kaempferol and quercetin exhibited broad inhibitory properties, while salicylic acid and methyl jasmonate demonstrated efficient inhibitory effects. Discussion: This study underscores the significance of the flavonoid biosynthesis pathway in M. notabilis' defense response against mulberry ring rot disease, offering a theoretical foundation for disease control measures.
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BACKGROUND: Lung cancer is cancer with the highest morbidity and mortality in the world and poses a serious threat to human health. Therefore, discovering new treatments is urgently needed to improve lung cancer prognosis. Small molecule inhibitors targeting the ubiquitin-proteasome system have achieved great success, in which deubiquitinase inhibitors have broad clinical applications. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. RESULTS: In this study, we identified a small molecule inhibitor of OTUD3, Rolapitant, by computer-aided virtual screening and biological experimental verification from FDA-approved drugs library. Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3. Quantitative proteomic profiling indicated that Rolapitant significantly upregulated the expression of death receptor 5 (DR5). Rolapitant also promoted lung cancer cell apoptosis through upregulating cell surface expression of DR5 and enhanced TRAIL-induced apoptosis. Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis. In the vivo assays, Rolapitant suppressed the growth of lung cancer xenografts in immunocompromised mice at suitable dosages without apparent toxicity. CONCLUSION: In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer.
Subject(s)
Endoplasmic Reticulum Chaperone BiP , Lung Neoplasms , Spiro Compounds , Humans , Mice , Animals , Cell Line, Tumor , Lung Neoplasms/drug therapy , Proteomics , Ubiquitin-Specific Proteases/metabolism , Apoptosis , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/pharmacologyABSTRACT
BACKGROUND: Compared to traditional fetal heart rate monitoring (FHR) for the outpatients in clinic, remote FHR monitoring shows real-time assessment of fetal wellbeing at home. The clinical function of remote FHR monitoring in pregnant wome in outpatient is still unclear. OBJECTIVE: To explore the feasibility of remote FHR self-monitoring in singleton pregnant women from southern China. STUDY DESIGN: This prospective cohort study was conducted at one tertiary center in southern China. Pregnant women used a mobile cardiotocogram device to measure the FHR at least once a week until delivery in the remote group. For the control group, pregnant women underwent traditional FHR monitoring once a week in the outpatient clinic. The rate of cesarean section, risk of postpartum hemorrhage and adverse neonatal outcomes were compared between the two groups. All the pregnant women completed a questionnaire survey to evaluate their acquisition of remote FHR self-monitoring. RESULTS: Approximately 500 women were recruited in the remote FHR self-monitoring group (remote group), and 567 women were recruited in the traditional FHR monitoring group (control group). The women in the remote FHR monitoring group were more likely to be nulliparous (P < 0.001), more likely to have a higher education level (P < 0.001) and more likely to be at high risk (P = 0.003). There was no significant difference in the risk of cesarean section (P = 0.068) or postpartum hemorrhage (P = 0.836) between the two groups. No difference in fetal complications was observed across groups, with the exception of the incidence of NICU stays, which was higher in the remote group (12.0% vs. 8.3%, P = 0.044). The questionnaire survey showed that the interval time (P = 0.001) and cost (P = 0.010) of fetal heart rate monitoring were lower in the remote group. Regarding age, prepregnancy BMI, risk factors, education level, maternal risk and household income, senior high school (OR 2.86, 95% CI 1.67-4.90, P < 0.001), undergraduate (OR 2.96, 95% CI 1.73-5.06, P < 0.001), advanced maternal age (OR 1.42, 95% CI 1.07-1.89, P = 0.015) and high-risk pregnancy (OR 1.61, 95% CI 1.11-2.35, P = 0.013) were independent factors for pregnant women to choose remote fetal monitoring. Multiparty (OR 0.33, 95% CI 0.21-0.51, P < 0.001), full-time motherhood (OR 0.47, 95% CI 0.33-0.678, P < 0.001) and high household income (OR 0.67, 95% CI 0.50-0.88, P = 0.004) were negatively correlated with the choice of remote FHR self-monitoring. CONCLUSION: Remote FHR self-monitoring technology has a lower cost and shows potential clinical efficacy for the outpatient setting in southern China. This approach does not increase the risk of cesarean section or adverse neonatal outcomes. It is acceptable among nulliparous pregnant women with a high education level, high household income or high risk. Further research is needed to assess the impact of this technology on obstetric outcomes in different health settings.
Subject(s)
Cesarean Section , Postpartum Hemorrhage , Female , Humans , Infant, Newborn , Pregnancy , Heart Rate, Fetal/physiology , Prospective Studies , Treatment Outcome , Remote ConsultationABSTRACT
Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the role and mechanisms of ALDOA in CRC are still unclear. In the current study, high expression levels and enzymatic activity of ALDOA were detected in CRC tissues and cell lines, indicating the clinical significance of ALDOA in human CRC. In addition, silencing ALDOA significantly impaired the proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, immunoprecipitation assays and mass spectrometry analysis identified the binding protein COPS6 of ALDOA. Furthermore, the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by COPS6 depletion, demonstrating COPS6 was required for ALDOA in mediating CRC progress. Moreover, the epithelial-mesenchymal transition (EMT) program and MAPK signaling pathway were found to be activated by ALDOA overexpression as well. In summary, our findings suggested that ALDOA facilitated the proliferation and metastasis of CRC by binding and regulating COPS6, inducing EMT, and activating the mitogen-activated protein kinase (MAPK) signaling pathway. The present study provided evidence for ALDOA as a promising potential biomarker for CRC.
Subject(s)
Colorectal Neoplasms , Mitogen-Activated Protein Kinases , Humans , Fructose-Bisphosphate Aldolase/genetics , Fructose-Bisphosphate Aldolase/metabolism , Cell Line, Tumor , Cell Movement , Signal Transduction , Cell Proliferation , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , COP9 Signalosome Complex/metabolism , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
OBJECTIVE: This study reviewed and analyzed the prenatal diagnosis experience of thalassemia in our center over the past decade and the abnormal ultrasonic characteristics of fetuses with hemoglobin (Hb) Bart's hydrops fetalis. METHODS: Pregnant women and their partners who tested positive for α0-thalassemia or were diagnosed with thalassemia intermedia (HbH diseases) underwent genetic counseling, and a prenatal diagnostic procedure for α-thalassemia was recommended. Ultrasonography was performed before prenatal diagnosis. RESULTS: Invasive prenatal α-thalassemia diagnosis and ultrasonography were performed in 1049 patients at risk for Hb Bart's hydrops fetalis syndrome at our hospital from 2012 to 2021. Chorionic villus sampling (CVS) was performed in 58 cases (5.5%), amniocentesis in 902 cases (86%), and cordocentesis in 89 cases (8.5%). Hb Bart's hydrops fetalis syndrome was diagnosed in 280 fetuses. The most common body cavity effusion was pericardial effusion, ascites, and fetal systemic edema. CONCLUSIONS: The extensive experience at our center shows that carrier screening, molecular diagnostics, genetic counseling, and prenatal diagnosis are effective measures to prevent Hb Bart's hydrops fetalis syndrome. The ultrasonographic abnormalities in fetuses with Hb Bart's hydrops are mainly caused by an increase in cardiac output, which leads to the body cavity effusion from various organs.
Subject(s)
Hemoglobins, Abnormal , alpha-Thalassemia , Humans , Pregnancy , Female , alpha-Thalassemia/diagnostic imaging , Hydrops Fetalis/diagnostic imaging , Retrospective Studies , Ultrasonics , Hospitals, Municipal , Prenatal Diagnosis/methods , Hemoglobins, Abnormal/genetics , Hemoglobins, Abnormal/adverse effects , Hemoglobins, Abnormal/analysisABSTRACT
Salmonella is one of the most important foodborne zoonotic pathogens, causing global morbidity and mortality in both humans and animals. Due to the extensive use of antimicrobials in food-producing animals, the antimicrobial resistance of Salmonella has attracted increasing attention globally. There have been many reports concerning the antimicrobial resistance of Salmonella from food-producing animals, meats and the environment. However, few studies on Salmonella from food-producing animals have been reported in Chongqing municipality, China. The aim of the present study was to determine the prevalence, serovar diversity, sequence types, and antimicrobial resistance of Salmonella isolated from livestock and poultry in Chongqing. Meanwhile, we also want to know the presence of ß-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes and quinolone resistance-determining region (QRDR) mutations of Salmonella isolates. A total of 129 Salmonella strains were recovered from 2,500 fecal samples at 41 farms from pigs, goats, beef cattle, rabbits, chickens, and ducks. Fourteen serovars were identified, with S. Agona and S. Derby being the dominant serovars. The 129 isolates had high resistance to doxycycline (87.6%), ampicillin (80.6%), tetracycline (79.8%), trimethoprim (77.5%), florfenicol (76.7%) chloramphenicol (72.9%), and trimethoprim-sulfamethoxazole (71.3%), but were susceptible to cefepime. A total of 114 (88.4%) isolates showed multidrug resistant phenotypes. The prevalence of ß-lactamase genes in Salmonella isolates was 89.9% (116/129), and among these isolates, 107 (82.9%) harbored blaTEM, followed by blaOXA (26, 20.2%), blaCTX-M (8, 6.2%), and blaCMY (3, 2.3%). In addition, qnrB, qnrD, qnrS, oqxA, oqxB, and aac(6')-Ib-cr were detected in 11, 2, 34, 34, 43, and 72 PMQR-producing isolates, respectively. Moreover, QRDR mutations were very common in PMQR-positive Salmonella isolates (97.2%, 70/72) with mutation(s) in parC or combinative mutations in gyrA and parC. More significantly, 32 extended spectrum beta-lactamase (ESBL)-producing isolates were identified, and 62.5% of them were found to harbor one to four PMQR genes. Furthermore, 11 sequence types were identified from the isolates, and most of ESBL-producing isolates were attributed to ST34 (15.6%) and ST40 (62.5%). The coexistence of PMQR genes with ß-lactamase genes and the extensive mutations in QRDR present in Salmonella isolates from food-producing animals suggest a potential threat to public health. Reasonable utilization and strict control strategies for antimicrobials in animal husbandry and animal treatment are necessary to reduce the emergence and dissemination of drug-resistant Salmonella isolates.
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OBJECTIVES: To assess the effectiveness, safety, and acceptability of postplacental insertion of GyneFix postpartum intrauterine device (PPIUD) in women undergoing cesarean section (C-section). STUDY DESIGN: We conducted a prospective cohort study at 14 hospitals in four eastern coastal provinces of China between September 2017 and November 2020. A total of 470 women who underwent C-section and consented to the postplacental insertion of GyneFix PPIUD were enrolled, and 400 completed the 12-month follow-up. Participants were interviewed in the wards after delivery and followed up at 42 days, and months 3, 6, and 12 after delivery. We used Pearl Index (PI) to measure the rate of contraceptive failure, life-table method to measure the rate of PPIUD discontinuation, including IUD expulsion, and Cox regression model to explore the risk factors associated with discontinuation of the device. RESULTS: Nine pregnancies were detected during the first year after GyneFix PPIUD insertion: seven were due to device expulsion and two occurred with PPIUD in situ. The PIs for overall 1-year pregnancy rate and pregnancies with IUD in situ were 2.3 (95% CI: 1.1-4.4) and 0.5 (95% CI: 0.1-1.9), respectively. The 6- and 12-month cumulative expulsion rates for PPIUD expulsion were 6.3% and 7.6%, respectively. The overall 1-year continuation rate was 86.6% (95% CI: 83.3-89.8). We did not identify any patient with insertion failure, uterine perforation, pelvic infection, or excess bleeding due to GyneFix PPIUD insertion. Women's age, education, occupation, previous history of C-section, parity, and breastfeeding were not associated with removal of GyneFix PPIUD in the first year of use. CONCLUSIONS: Postplacental insertion of GyneFix PPIUD is effective, safe, and acceptable for women undergoing C-section. Expulsion is the most common reason for GyneFix PPIUD discontinuation and pregnancy. The expulsion rate for GyneFix PPIUD is lower than that for framed IUDs, but more evidence is needed for a firm verdict.
Subject(s)
Intrauterine Devices, Copper , Intrauterine Devices , Pregnancy , Female , Humans , Cesarean Section , Prospective Studies , Postpartum Period , Intrauterine Device Expulsion , Parity , China , Intrauterine Devices, Copper/adverse effectsABSTRACT
PURPOSE: Adriamycin is a novel chemotherapeutic agent of great benefit for treating breast cancer. However, adriamycin -resistance remains a major obstacle. The vital Glutathione transferase P1 (GSTPi) inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) has recently shown antitumor activity in various cancers. In this study, we analyzed the effect of NBDHEX and adriamycin combination against breast cancer in vitro and in vivo. METHODS: CCK-8 assay was performed to test cell viability. The location and expression level of GSTpi was determined by immunofluorescence and Western blot in cells and immunohistochemistry staining in tissues. The enzyme activity test was applied to detect the effect of NBDHEX on the activity of GSTpi. The apoptosis related proteins' expression was tested using Western blot. The phosphorylation sites of GSTpi were detected by mass spectrometry. Antitumor effects of single treatment or co-administration of adriamycin and NBDHEX were evaluated in nude mice. RESULTS: NBDHEX treatment inhibited GSTpi enzyme activity and co-administration of adriamycin and NBDHEX promoted apoptosis of adriamycin-resistance breast cancer cell. Moreover, drug combination of NBDHEX and adriamycin significantly enhanced tumor growth inhibition compared with single agent. CONCLUSION: NBDHEX serves as a good candidate for combination with adriamycin, offering new insights for breast cancer treatment.
Subject(s)
Breast Neoplasms , Doxorubicin , Glutathione S-Transferase pi , Oxadiazoles , Animals , Mice , Breast Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Mice, Nude , Doxorubicin/therapeutic useABSTRACT
In this study, the larva and pupa of Agrilusadelphinus are described and illustrated. DNA barcoding (COI gene) was used to associate the larval and pupal stages with adults based on the maximum-likelihood method. In the resulting phylogenetic tree, species from the same species-group were found to be clustered on a branch with high support value. To better understand A.adelphinus, the complete mitochondrial genome of this species was also sequenced and annotated. Comparing this genome to the known mitogenomes of Agrilus species, the newly sequenced genome is shorter, with 15,732 bp. However, its whole mitogenome composition and gene orientation were consistent with that of most species of Buprestidae. In the mitogenome of A.adelphinus, the ATGATAG sequence was observed between ATP8 and ATP6, which is ATGATAA in other insect mitogenomes. Leu2, Phe, Ile, Gly, and Ser2 were the five most frequently encoded amino acids. The results further prove that DNA barcoding can remove the limitation of traditional taxonomy which cannot identify to species all developmental stages. This study also provides valuable molecular and morphological data for species identification and phylogenetic analyses of the genus Agrilus.
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Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by obesity, mental retardation, retinal dystrophy, hypogenitalism and renal and polydactyly malformations. The last two malformations may be observed antenatally and are highly variable, making the prenatal diagnosis of BBS challenging. The present study investigated the molecular etiology of BBS and validated a method for prenatal diagnosis. A Chinese couple who had conceived two fetuses with multiple malformations, including hyperechogenic kidneys, polydactyly, cardiac malformation and abdominal abnormalities, presented at the Prenatal Diagnosis Center of Boai Hospital of Zhongshan Affiliated to Southern Medical University (Zhongshan, China) in November 2018. BBS was suspected and whole-exome sequencing was performed for the second fetus. Two novel compound heterozygous variants were detected in the BBS10 gene, c.784_785delGA from the father and c.1812dupT from the mother, which are probably causative of the pathogenesis of BBS. This finding provided a basis for genetic counseling and prenatal diagnosis for the couple and enriched the variation spectrum of the BBS10 gene. The ultrasonic findings of the fetal abdomen are the first reported in fetuses with BBS, expanding the antenatal phenotypes of BBS.
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ADP-ribosylation is a well-established post-translational modification that is inherently connected to diverse processes, including DNA repair, transcription, and cell signaling. The crucial roles of mono-ADP-ribosyltransferases (mono-ARTs) in biological processes have been identified in recent years by the comprehensive use of genetic engineering, chemical genetics, and proteomics. This review provides an update on current methodological advances in the study of these modifiers. Furthermore, the review provides details on the function of mono ADP-ribosylation. Several mono-ARTs have been implicated in the development of cancer, and this review discusses the role and therapeutic potential of some mono-ARTs in cancer.
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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. MiRNAs are involved in the development and progression of a wide range of cancers. Among such cancer-associated miRNAs, miR-381 has been a major focus of research. The expression pattern and role of miR-381 vary among different cancer types. MiR-381 modulates various cellular behaviours in cancer, including proliferation, apoptosis, cell cycle progression, migration and invasion. MiR-381 is also involved in angiogenesis and lymphangiogenesis, as well as in the resistance to chemotherapy and radiotherapy. MiR-381 itself is regulated by several factors, such as long noncoding RNAs, circular RNAs and cytokines. Aberrant expression of miR-381 in blood samples indicates that it can be used as a diagnostic marker in cancer. Tissue miR-381 expression may serve as a prognostic factor for the clinicopathological characteristics of cancers and survival of patients. Metformin and icaritin regulate miR-381 expression and present anticancer properties. This review comprehensively summarizes the effect of miR-381 on tumour biological behaviours, as well as the clinical application potential of miR-381 for the treatment of cancer.
Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/metabolism , Neoplasms/pathology , RNA, CircularABSTRACT
Ammonia (NH3) emissions, mainly from agricultural sources, generate substantial health damage due to the adverse effects on air quality. NH3 emission reduction strategies are still far from being effective. In particular, a growing trade network in this era of globalization offers untapped emission mitigation potential that has been overlooked. Here we show that about one-fourth of global agricultural NH3 emissions in 2012 are trade-related. Globally they induce 61 thousand PM2.5-related premature mortalities, with 25 thousand deaths associated with crop cultivation and 36 thousand deaths with livestock production. The trade-related health damage network is regionally integrated and can be characterized by three trading communities. Thus, effective cooperation within trade-dependent communities will achieve considerable NH3 emission reductions allowed by technological advancements and trade structure adjustments. Identification of regional communities from network analysis offers a new perspective on addressing NH3 emissions and is also applicable to agricultural greenhouse gas emissions mitigation.
Subject(s)
Agriculture/methods , Air Pollutants/analysis , Ammonia/analysis , Environmental Monitoring/methods , Fertilizers/analysis , Livestock/physiology , Manure/analysis , Air Pollutants/poisoning , Ammonia/poisoning , Animals , Fertilizers/adverse effects , Greenhouse Gases/analysis , Greenhouse Gases/poisoning , InternationalityABSTRACT
Poly ADP ribose polymerases (PARPs) catalyze the modification of acceptor proteins, DNA, or RNA with ADP-ribose, which plays an important role in maintaining genomic stability and regulating signaling pathways. The rapid development of PARP1/2 inhibitors for the treatment of ovarian and breast cancers has advanced research on other PARP family members for the treatment of cancer. This paper reviews the role of PARP family members (except PARP1/2 and tankyrases) in cancer and the underlying regulatory mechanisms, which will establish a molecular basis for the clinical application of PARPs in the future.
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PURPOSE: Colorectal cancer (CRC) is one of the most frequent tumors and causes of mortality worldwide. Ubiquitin ligase was reported to regulate multiple cellular processes, including tumorigenesis. As ubiquitin E3 ligases, RING-finger proteins play a key role in physiological and pathophysiological processes. METHODS: We compared the expression levels of RNF128 in CRC tissues by western-blotting and qRT-PCR. Knockdown and overexpression of RNF128 were performed to examine its effect on proliferation and metastasis of CRC cells. Using western blot and co-immunoprecipitation assays, we explored the possible mechanisms underlying the effect of RNF128 in CRC cells. RESULTS: We found that the expression level of RNF128 was correlated with the CRC tumorigenicity. Overexpression or knockdown of RNF128 suppressed or elevated CRC cell proliferation, migration and invasion, respectively. We further determined that RNF128 regulated ß-catenin ubiquitination and thus inhibited Wnt/ß-catenin signaling in CRC cells. CONCLUSION: Our research demonstrated that RNF128 inhibited cell proliferation and metastasis of CRC cells via Wnt/ß-catenin signaling-mediated deubiquitination.
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OBJECTIVE: To evaluate the value of fasting plasma glucose (FPG) value in the first prenatal visit to diagnose gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Medical records of 17,186 pregnant women attending prenatal clinics in 13 hospitals in China, including the Peking University First Hospital (PUFH), were examined. Patients with pre-GDM were excluded; data for FPG at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test (OGTT) performed between 24 and 28 weeks of gestation were collected and analyzed. RESULTS: The median ± SD FPG value was 4.58 ± 0.437. FPG decreased with increasing gestational age. FPG level at the first prenatal visit was strongly correlated with GDM diagnosed at 24-28 gestational weeks (χ(2) = 959.3, P < 0.001). The incidences of GDM were 37.0, 52.7, and 66.2%, respectively, for women with FPG at the first prenatal visit between 5.10 and 5.59, 5.60 and 6.09, and 6.10-6.99 mmol/L. The data of PUFH were not statistically different from other hospitals. CONCLUSIONS: Pregnant women (6.10 ≤ FPG < 7.00 mmol/L) should be considered and treated as GDM to improve outcomes; for women with FPG between 5.10 and 6.09 mmol/L, nutrition and exercise advice should be provided. An OGTT should be performed at 24-28 weeks to confirm or rule out GDM. Based on our data, we cannot support an FPG value ≥5.10 mmol/L at the first prenatal visit as the criterion for diagnosis of GDM.