Case Report: First attempt by off-label use of tenecteplase to treat acute extensive portal venous system thrombosis

Acute extensive portal venous system thrombosis (PVST) can cause lethal complications. Herein, we have for the first time reported the use of anticoagulation combined with systemic thrombolysis by tenecteplase in a male patient with a diagnosis of acute extensive PVST but without liver cirrhosis. After thrombolytic therapy, abdominal pain obviously alleviated. However, urinary bleeding developed, which was reversible by stopping thrombolytic drugs. Finally, this case developed cavernous transformation of the portal vein without portal venous recanalization. In future, the efficacy and safety of tenecteplase should be explored in acute extensive PVST cases

Opposing Actions of Adrenocorticotropic Hormone and Glucocorticoids on UCP1-Mediated Respiration in Brown Adipocytes

Brown fat is a potential target in the treatment of metabolic disorders as recruitment and activation of this thermogenic organ increases energy expenditure and promotes satiation. A large variety of G-protein coupled receptors, known as classical drug targets in pharmacotherapy, is expressed in brown adipocytes. In the present study, we analyzed transcriptome data for the expression of these receptors to identify potential pathways for the recruitment and activation of thermogenic capacity in brown fat. Our analysis revealed 12 Gs-coupled receptors abundantly expressed in murine brown fat. We screened ligands for these receptors in brown adipocytes for their ability to stimulate UCP1-mediated respiration and Ucp1 gene expression. Adrenocorticotropic hormone (ACTH), a ligand for the melanocortin 2 receptor (MC2R), turned out to be the most potent activator of UCP1 whereas its capability to stimulate Ucp1 gene expression was comparably low. Adrenocorticotropic hormone is the glandotropic hormone of the endocrine hypothalamus–pituitary–adrenal-axis stimulating the release of glucocorticoids in response to stress. In primary brown adipocytes ACTH acutely increased the cellular respiration rate similar to isoproterenol, a β-adrenergic receptor agonist. The effect of ACTH on brown adipocyte respiration was mediated via the MC2R as confirmed by using an antagonist. Inhibitor-based studies revealed that ACTH-induced respiration was dependent on protein kinase A and lipolysis, compatible with a rise of intracellular cAMP in response to ACTH. Furthermore, it is dependent on UCP1, as cells from UCP1-knockout mice did not respond. Taken together, ACTH is a non-adrenergic activator of murine brown adipocytes, initiating the canonical adenylyl cyclase–cAMP–protein kinase A-lipolysis-UCP1 pathway, and thus a potential target for the recruitment and activation of thermogenic capacity. Based on these findings in primary cell culture, the physiological significance might be that cold-induced ACTH in concert with norepinephrine released from sympathetic nerves contributes to BAT thermogenesis. Notably, dexamethasone attenuated isoproterenol-induced respiration. This effect increased gradually with the duration of pretreatment. In vivo, glucocorticoid release triggered by ACTH might oppose beta-adrenergic stimulation of metabolic fuel combustion in BAT and limit stress-induced hyperthermia

New dinosaur egg material from Yunxian, Hubei Province, China resolves the classification of dendroolithid eggs

The oofamily Dendroolithidae is a distinct group of dinosaur eggs reported from China and Mongolia, which is characterized by branched eggshell units and irregular pore canals. The ootaxonomic inferences, however, were rarely discussed until now. A colonial nesting site was recently uncovered from the Qinglongshan region, Yunxian, Hubei Province, China. More than 30 dendroolithid egg clutches outcrop on the Tumiaoling Hill, including an extremely gigantic clutch containing 77 eggs. All clutches were exposed in the Upper Cretaceous fluvial-deposited Gaogou For mation. In this study, we emend the diagnosis of the oogenus Placoolithus and assign all dendroolithid eggs from the Tumiaoling Hill to a newly emended oospecies Placoolithus tumiaolingensis that shows greatly variable eggshell microstructure. Moreover, our study also disentangles the previous vexing classification of dendroolithid eggs. We conclude that Dendroolithus tumiaolingensis, D. hongzhaiziensis, and Paradendroolithus qinglongshanensis, all of which were previously reported from Yunxian, should be assigned to the newly emended oospecies Placoolithus tumiaolingensis

Rare Copy Number Variations in a Chinese Cohort of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is heterogeneous in symptom and etiology. Rare copy number variations (CNVs) are important genetic factors contributing to ASD. Currently chromosomal microarray (CMA) detecting CNVs is recommended as a first-tier diagnostic assay, largely based on research in North America and Europe. The feature of rare CNVs has not been well characterized in ASD cohorts from non-European ancestry. In this study, high resolution CMA was utilized to investigate rare CNVs in a Chinese cohort of ASD (n = 401, including 177 mildly/moderately and 224 severely affected individuals), together with an ancestry-matched control cohort (n = 197). Diagnostic yield was about 4.2%, with 17 clinically significant CNVs identified in ASD individuals, of which 12 CNVs overlapped with recurrent autism risk loci or genes. Autosomal rare CNV burden analysis showed an overrepresentation of rare loss events in ASD cohort, whereas the rate of rare gain events correlated with the phenotypic severity. Further analysis showed rare losses disrupting genes highly intolerant of loss-of-function variants were enriched in the ASD cohort. Among these highly constrained genes disrupted by rare losses, RIMS2 is a promising candidate contributing to ASD risk. This pilot study evaluated clinical utility of CMA and the feature of rare CNVs in Chinese ASD, with candidate genes identified as potential risk factors

Expounding the role of tick in Africa swine fever virus transmission and seeking effective prevention measures: A review

African swine fever (ASF), a highly contagious, deadly infectious disease, has caused huge economic losses to animal husbandry with a 100% mortality rate of the most acute and acute infection, which is listed as a legally reported animal disease by the World Organization for Animal Health (OIE). African swine fever virus (ASFV) is the causative agent of ASF, which is the only member of the Asfarviridae family. Ornithodoros soft ticks play an important role in ASFV transmission by active biological or mechanical transmission or by passive transport or ingestion, particularly in Africa, Europe, and the United States. First, this review summarized recent reports on (1) tick species capable of transmitting ASFV, (2) the importance of ticks in the transmission and epidemiological cycle of ASFV, and (3) the ASFV strains of tick transmission, to provide a detailed description of tick-borne ASFV. Second, the dynamics of tick infection with ASFV and the tick-induced immune suppression were further elaborated to explain how ticks spread ASFV. Third, the development of the anti-tick vaccine was summarized, and the prospect of the anti-tick vaccine was recapitulated. Then, the marked attenuated vaccine, ASFV-G-ΔI177L, was compared with those of the anti-tick vaccine to represent potential therapeutic or strategies to combat ASF

比利时

peer reviewedUltra-performance convergence chromatography is an environmentally-friendly analytical method that uses dramatically reduced amounts of organic solvents. In addition, a robust and highly sensitive chiral separation method was developed for the novel chiral acaricide cyflumetofen by using ultra-performance convergence chromatography coupled with tandem mass spectrometry, which shows that stereoisomer recoveries determined for various apple parts ranged from 78.3% to 119.9%, with the relative standard deviations being lower than 14.0%. The half-lives of (-)-cyflumetofen and (+)-cyflumetofen obtained under 5-fold applied dosage equal to 22.13 and 22.23 days, respectively. For 1.5-fold applied dosage, the respective values were determined as 22.42 and 23.64 days, i.e., the degradation of (-)-cyflumetofen was insignificantly favored over that of its enantiomer. Importantly, cyflumetofen was unevenly distributed in apples, with its relative contents in apple peel, peduncle, and pomace equal to 50%, 22%, and 16%, respectively. The proposed method can be used to efficiently separate and quantify chiral pesticide with advantages of a shorter analysis time, greater sensitivity, and better environmental compatibility. Additionally, the consumption of apples with residue of cyflumetofen did not pose a health risk to the population if the cyflumetofen applied under satisfactory agricultural practices after the long-term dietary risk assessment

Metagenomic Analysis of Bacteria, Fungi, Bacteriophages, and Helminths in the Gut of Giant Pandas

To obtain full details of gut microbiota, including bacteria, fungi, bacteriophages, and helminths, in giant pandas (GPs), we created a comprehensive microbial genome database and used metagenomic sequences to align against the database. We delineated a detailed and different gut microbiota structures of GPs. A total of 680 species of bacteria, 198 fungi, 185 bacteriophages, and 45 helminths were found. Compared with 16S rRNA sequencing, the dominant bacterium phyla not only included Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria but also Cyanobacteria and other eight phyla. Aside from Ascomycota, Basidiomycota, and Glomeromycota, Mucoromycota, and Microsporidia were the dominant fungi phyla. The bacteriophages were predominantly dsDNA Myoviridae, Siphoviridae, Podoviridae, ssDNA Inoviridae, and Microviridae. For helminths, phylum Nematoda was the dominant. In addition to previously described parasites, another 44 species of helminths were found in GPs. Also, differences in abundance of microbiota were found between the captive, semiwild, and wild GPs. A total of 1,739 genes encoding cellulase, β-glucosidase, and cellulose β-1,4-cellobiosidase were responsible for the metabolism of cellulose, and 128,707 putative glycoside hydrolase genes were found in bacteria/fungi. Taken together, the results indicated not only bacteria but also fungi, bacteriophages, and helminths were diverse in gut of giant pandas, which provided basis for the further identification of role of gut microbiota. Besides, metagenomics revealed that the bacteria/fungi in gut of GPs harbor the ability of cellulose and hemicellulose degradation

Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers

Background: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers.Methods: This study was conducted in two parts. Study I was a dose-escalating (5–15 mg) study. For each dose, 15 participants were randomized into three groups (total n = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay.Results: Vicagrel (5–15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (~10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day).Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. The study was registered at http://www.chictr.org.cn (ChiCTR-IIR-16009260)