Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

• MeSH
• apoptóza MeSH
• extracelulárním signálem regulované MAP kinasy MeSH
• krysa rodu rattus MeSH
• messenger RNA MeSH
• poranění mozku * MeSH
• potkani Sprague-Dawley MeSH
• reperfuzní poškození * metabolismus   MeSH
• srdeční zástava * komplikace   MeSH
• stres endoplazmatického retikula MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

T-2 toxin, a major compound of trichothecenes, inhibits protein synthesis and induces inflammation and cell apoptosis through the activation of MAPK pathway. The JAK/STAT pathway has recently been shown to be downstream targets of trichothecenes. However, whether there is any crosstalk between JNK and JAK/STAT pathways in trichothecene toxicity has not been studied. In the present study, we explored this potential in RAW264.7 cells treated with T-2 toxin. Our results revealed a crosstalk between JNK1 and STAT3 after T-2 toxin treatment, which was mediated by K-Ras. T-2 toxin treatment resulted in rapid phosphorylation, and more importantly, JNK1-STAT3 signaling pathway was shown to maintain the normal function of the mitochondria and to inhibit T-2 toxin-induced apoptosis. Therefore, this pathway was considered to be a potential cell survival pathway. Breakdown and degranulation of ribosomes in the rough endoplasmic reticulum and swelling of mitochondria were clearly visible after the cells had been incubated with T-2 toxin for 12h. Our data suggest that T-2 toxin had a Janus face: it induced both apoptotic and cell survival pathways. These results suggest that the crosstalk and the balance between MAPK and JAK/STAT pathway might be involved in T-2 toxin-induced apoptosis in RAW264.7 cells.

• MeSH
• anthraceny farmakologie   MeSH
• apoptóza účinky léků   MeSH
• biologické modely MeSH
• buněčné linie MeSH
• cytokiny genetika   metabolismus   MeSH
• fluorescenční protilátková technika MeSH
• fosforylace účinky léků   MeSH
• Janus kinasy metabolismus   MeSH
• kinetika MeSH
• makrofágy cytologie   účinky léků   metabolismus   ultrastruktura   MeSH
• mitochondrie účinky léků   metabolismus   ultrastruktura   MeSH
• mitogenem aktivovaná proteinkinasa 8 metabolismus   MeSH
• myši MeSH
• ras proteiny metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• ribozomy účinky léků   metabolismus   ultrastruktura   MeSH
• signální transdukce * účinky léků   MeSH
• T-2 toxin farmakologie   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The escalation of antibiotic resistance has revitalized bacteriophage (phage) therapy. Recently, phage therapy has been gradually applied in medicine, agriculture, food, and environmental fields due to its distinctive features of high efficiency, specificity, and environmental friendliness compared to antibiotics. Likewise, phage therapy also holds great promise in controlling pathogenic bacteria in aquaculture. The application of phage therapy instead of antibiotics to eliminate pathogenic bacteria such as Vibrio, Pseudomonas, Aeromonas, and Flavobacterium and to reduce fish mortality in aquaculture has been frequently reported. In this context, the present review summarizes and analyzes the current status of phage therapy in aquaculture, focusing on the key parameters of phage application, such as phage isolation, selection, dosage, and administration modes, and introducing the strategies and methods to boost efficacy and restrain the emergence of resistance. In addition, we discussed the human safety, environmental friendliness, and techno-economic practicability of phage therapy in aquaculture. Finally, this review outlines the current challenges of phage therapy application in aquaculture from the perspectives of phage resistance, phage-mediated resistance gene transfer, and effects on the host immune system.

• MeSH
• antibakteriální látky MeSH
• bakteriofágy * genetika   MeSH
• fágová terapie * MeSH
• Vibrio * MeSH
• vodní hospodářství metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Excretion, disposition, and metabolism of [(3)H]-quinocetone in rats, pigs, broilers, and carp following oral administration were investigated. After a single p.o. dose, total radioactivity was rapidly excreted, with ⩾94% in all species within 14 days. Fecal excretion of radioactivity was 68% and 65% of the administered dose in rats and pigs, respectively, with the remainder excreted in the urine. Six hours after the last of seven daily oral administrations of (3)H-labeled QCT, radioactivity was found to be distributed throughout all tissues, with the majority of radioactivity cleared within 7 days, and elimination was the slowest from the liver and kidney. QCT was extensively metabolized in all of the species, and the primary changes included N-O group reduction, carbonyl group reduction, double bond reduction, and hydroxylation. The major tissue metabolites of QCT were Q2, Q4, Q5, Q8, and Q9 in rats; Q1, Q2, Q3, Q4, and Q5 in pigs; Q1, Q2, Q3, Q4, and Q7 in broilers; and Q1, Q2 in carp. This confirmed the potential link between QCT metabolism through N-O group reduction and its organ toxicity. The results of the present study provide important data that could help understand the relationship between the toxicities and metabolic disposition of QCT.

• MeSH
• aplikace orální MeSH
• chinoxaliny aplikace a dávkování   metabolismus   farmakokinetika   toxicita   MeSH
• feces MeSH
• kapři MeSH
• kur domácí MeSH
• potkani Wistar MeSH
• Sus scrofa MeSH
• tkáňová distribuce MeSH
• tritium farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Classifying diseases into ICD codes has mainly relied on human reading a large amount of written materials, such as discharge diagnoses, chief complaints, medical history, and operation records as the basis for classification. Coding is both laborious and time consuming because a disease coder with professional abilities takes about 20 minutes per case in average. Therefore, an automatic code classification system can significantly reduce the human effort. Objectives: This paper aims at constructing a machine learning model for ICD-10 coding, where the model is to automatically determine the corresponding diagnosis codes solely based on free-text medical notes. Methods: In this paper, we apply Natural Language Processing (NLP) and Recurrent Neural Network (RNN) architecture to classify ICD-10 codes from natural language texts with supervised learning. Results: In the experiments on large hospital data, our predicting result can reach F1-score of 0.62 on ICD-10-CM code. Conclusion: The developed model can significantly reduce manpower in coding time compared with a professional coder.

• MeSH
• automatizované zpracování dat metody   MeSH
• deep learning * MeSH
• elektronické zdravotní záznamy MeSH
• mezinárodní klasifikace nemocí * MeSH
• neuronové sítě MeSH
• strojové učení MeSH
• ukládání a vyhledávání informací metody   statistika a číselné údaje   MeSH
• vizualizace dat MeSH
• zpracování přirozeného jazyka MeSH
• Publikační typ
• práce podpořená grantem MeSH

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

• MeSH
• antibakteriální látky terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   epidemiologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• nádory žaludku * prevence a kontrola   epidemiologie   mikrobiologie   MeSH
• omeprazol * terapeutické užití   aplikace a dávkování   MeSH
• organokovové sloučeniny terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• tetracyklin terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Čína MeSH

Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.

• MeSH
• adenokarcinom genetika   patologie   MeSH
• Bayesova věta MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• nádory plic genetika   patologie   MeSH
• spinocelulární karcinom genetika   patologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The bla(CTX-M-15) gene, encoding the globally dominant CTX-M-15 extended-spectrum β-lactamase, has generally been found in a 2.971-kb ISEcp1-bla(CTX-M-15)-orf477Δ transposition unit, with ISEcp1 providing a promoter. In available IncF plasmid sequences from Escherichia coli, this transposition unit interrupts a truncated copy of transposon Tn2 that lies within larger multiresistance regions. In E. coli, bla(CTX-M-15) is also commonly associated with IncI1 plasmids and here three such plasmids from E. coli clinical isolates from western Sydney 2006-2007 have been sequenced. The plasmid backbones are organised similarly to those of other IncI1 plasmids, but have insertions and/or deletions and sequence differences. Each plasmid also has a different insertion carrying bla(CTX-M-15). pJIE113 (IncI1 sequence type ST31) is almost identical to plasmids isolated from the 2011 E. coli O104:H4 outbreak in Europe, where the typical bla(CTX-M-15) transposition unit interrupts a complete Tn2 inserted directly in the plasmid backbone. In the novel plasmid pJIE139 (ST88), ISEcp1-blaC(TX-M-15)-orf477Δ lies within a Tn2/3 hybrid transposon. Homologous recombination could explain movement of ISEcp1-bla(CTX-M-15)-orf477Δ between copies of Tn2 on IncF and IncI1 plasmids and generation of the Tn2/3 hybrid. pJIE174 (ST37) is almost identical to pESBL-12 from the Netherlands and in these plasmids bla(CTX-M-15) is flanked by two copies of IS26 that truncate the transposition unit within a larger region bounded by the ends of Tn2. bla(CTX-M-15) and the associated ISEcp1-derived promoter may be able to move from this structure by the actions of IS26, independently of both ISEcp1 and Tn2.

• MeSH
• anotace sekvence MeSH
• beta-laktamasy genetika   MeSH
• beta-laktamová rezistence genetika   MeSH
• Escherichia coli enzymologie   genetika   MeSH
• plazmidy genetika   MeSH
• proteiny z Escherichia coli genetika   MeSH
• regulační oblasti nukleových kyselin MeSH
• replikace DNA MeSH
• sekvenční analýza DNA MeSH
• transpozibilní elementy DNA MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. RESULTS: Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense, which has two orthologs of AtVND7, the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. CONCLUSIONS: The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.

• MeSH
• Arabidopsis genetika   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genom rostlinný * MeSH
• genom * MeSH
• Magnoliopsida genetika   MeSH
• molekulární evoluce * MeSH
• rostlinné proteiny genetika   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza MeSH
• syntenie MeSH
• transkripční faktory genetika   MeSH
• xylém MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Čína MeSH

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

• MeSH
• Asijci genetika   MeSH
• běloši genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci etnologie   genetika   MeSH
• genotyp MeSH
• HLA antigeny genetika   MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování chromozomů * MeSH
• nádory plic etnologie   genetika   MeSH
• peptidy genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH