Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex i...Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex interactions between important neurohormonal mechanisms that try but ultimately fail to sustain cardiac output. The most prominent such mechanism is the sympathetic(adrenergic) nervous system(SNS), whose activity and outflow are greatly elevated in HF. SNS hyperactivity confers significant toxicity to the failing heart and markedly increases HF morbidity and mortality via excessive activation of adrenergic receptors, which are G protein-coupled receptors. Thus, ligand binding induces their coupling to heterotrimeric G proteins that transduce intracellular signals. G protein signaling is turned-off by the agonist-bound receptor phosphorylation courtesy of G protein-coupled receptor kinases(GRKs), followed by βarrestin binding, which prevents the GRK-phosphorylated receptor from further interaction with the G proteins and simultaneously leads it inside the cell(receptor sequestration). Recent evidence indicates that adrenal GRK2 and βarrestins can regulate adrenal catecholamine secretion, thereby modulating SNS activity in HF. The present review gives an account of all these studies on adrenal GRKs and βarrestins in HF and discusses the exciting new therapeutic possibilities for chronic HF offered by targeting these proteins pharmacologically.展开更多
On July 2, 2019, President Xi Jinping held talks with President Recep Tayyip Erdogan of Turkey in Beijing. Xi Jinping noted that the two countries should consolidate the political foundation underlying the development...On July 2, 2019, President Xi Jinping held talks with President Recep Tayyip Erdogan of Turkey in Beijing. Xi Jinping noted that the two countries should consolidate the political foundation underlying the development of the China-Turkey strategic cooperative relations to keep bilateral relations on a healthy and stable track, and should take concrete measures to promote counter-terrorism cooperation. The Chinese side appreciates Recep Tayyip Erdogan’s reiteration on many occasions about not allowing anti-China separatist activities instigated by any force in Turkey, and highly values the repeated emphasis by the Turkish side on supporting the Chinese side’s counter-terrorism efforts. The Chinese side is ready to strengthen cooperation with the Turkish side in the field of international counter-terrorism.展开更多
AIM:To compare efficacy of proton pump inhibitors(PPIs)with H2-receptor antagonists(H2RAs)plus prokinetics(Proks)for dysmotility-like symptoms in functional dyspepsia(FD).METHODS:Subjects were randomized to receive op...AIM:To compare efficacy of proton pump inhibitors(PPIs)with H2-receptor antagonists(H2RAs)plus prokinetics(Proks)for dysmotility-like symptoms in functional dyspepsia(FD).METHODS:Subjects were randomized to receive openlabel treatment with either rabeprazole 10 mg od(n= 57)or famotidine 10 mg bid plus mosapride 5 mg tid(n=57)for 4 wk.The primary efficacy endpoint was change(%)from baseline in total dysmotility-like dyspepsia symptom score.The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS:The improvement in dysmotility-like dyspep-sia symptom score on day 28 was significantly greater in the rabeprazole group(22.5%±29.2%of baseline) than the famotidine+mosapride group(53.2%± 58.6%of baseline,P<0.0001).The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status.Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine+mosapride group(87.7%vs 59.6%,P= 0.0012).Rabeprazole therapy was the only significant predictor of treatment response(P<0.0001),defined as a total symptom score improvement≥50%.CONCLUSION:PPI monotherapy improves dysmotility-like symptoms significantly better than H2RAs plus Proks,and should be the treatment of first choice for Japanese FD.展开更多
Spinosyns,including spinosad and spinetoram,act on the insect central nervous system,gradually paralyzing or destroying the target insect.Spinosad resistance is associated with loss-of-function mutations in the nicoti...Spinosyns,including spinosad and spinetoram,act on the insect central nervous system,gradually paralyzing or destroying the target insect.Spinosad resistance is associated with loss-of-function mutations in the nicotinic acetylcholine receptor(nAChR)α6 subunit in a number of agricultural pests.Using gene editing,nAChRα6 has been verified as a target for spinosyns in five insect species.Recently,a point mutation(G275E)in exon 9 of nAChRα6 was identified in spinosad-resistant strains of Thrips palmi and Tuta absoluta.To date,no in vivo functional evidence has been obtained to support that this mutation is involved in spinosyn resistance in lepidopteran pests.In this study,the G275E mutation was introduced into the nAChR of Spodoptera exigua using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology.Reverse transcriptase-polymerase chain reaction and sequencing confirmed that this mutation was present in exon 9 of the nAChR transcripts in the edited 275E strain.The results of bioassays showed that the 275E strain was highly resistant to spinosad(230-fold)and spinetoram(792-fold)compared to the unedited background strain,directly confirming that the G275E mutation of the nAChRα6 subunit confers high levels of spinosyn resistance in S.exigua.Inheritance analysis showed that the resistance trait is autosomal and incompletely recessive.This study employs a reverse genetics approach to validate the functional role played by the G275E mutation in nAChRα6 of S.exigua in spinosyns resistance and provides another example of the use of CRISPR/Cas9 gene-editing technology to confirm the role played by candidate target site mutations in insecticide resistance.展开更多
以自建的英国、美国、印度和新加坡四国英文媒体(以下简称“英美印新英文媒体”)有关“人类命运共同体”的新闻报道语料库为基础,采用基于语料库的批评话语分析方法,分析“人类命运共同体”英译在英美印新英文媒体的传播与接受效果。研...以自建的英国、美国、印度和新加坡四国英文媒体(以下简称“英美印新英文媒体”)有关“人类命运共同体”的新闻报道语料库为基础,采用基于语料库的批评话语分析方法,分析“人类命运共同体”英译在英美印新英文媒体的传播与接受效果。研究发现,“人类命运共同体”理念在英美印新英文媒体中得到了广泛关注,其最新译名“community with a shared future for mankind”的使用频率愈来愈高,有取代其他译名的趋势。但由于受意识形态偏见和地缘政治等因素的影响,“人类命运共同体”理念在英美印新英文媒体中的接受情况还存在一定差距。为此,建议优化中国特色外交话语国际传播策略,希冀为“人类命运共同体”理念更好地“走出去”贡献力量。展开更多
文摘Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex interactions between important neurohormonal mechanisms that try but ultimately fail to sustain cardiac output. The most prominent such mechanism is the sympathetic(adrenergic) nervous system(SNS), whose activity and outflow are greatly elevated in HF. SNS hyperactivity confers significant toxicity to the failing heart and markedly increases HF morbidity and mortality via excessive activation of adrenergic receptors, which are G protein-coupled receptors. Thus, ligand binding induces their coupling to heterotrimeric G proteins that transduce intracellular signals. G protein signaling is turned-off by the agonist-bound receptor phosphorylation courtesy of G protein-coupled receptor kinases(GRKs), followed by βarrestin binding, which prevents the GRK-phosphorylated receptor from further interaction with the G proteins and simultaneously leads it inside the cell(receptor sequestration). Recent evidence indicates that adrenal GRK2 and βarrestins can regulate adrenal catecholamine secretion, thereby modulating SNS activity in HF. The present review gives an account of all these studies on adrenal GRKs and βarrestins in HF and discusses the exciting new therapeutic possibilities for chronic HF offered by targeting these proteins pharmacologically.
文摘On July 2, 2019, President Xi Jinping held talks with President Recep Tayyip Erdogan of Turkey in Beijing. Xi Jinping noted that the two countries should consolidate the political foundation underlying the development of the China-Turkey strategic cooperative relations to keep bilateral relations on a healthy and stable track, and should take concrete measures to promote counter-terrorism cooperation. The Chinese side appreciates Recep Tayyip Erdogan’s reiteration on many occasions about not allowing anti-China separatist activities instigated by any force in Turkey, and highly values the repeated emphasis by the Turkish side on supporting the Chinese side’s counter-terrorism efforts. The Chinese side is ready to strengthen cooperation with the Turkish side in the field of international counter-terrorism.
文摘AIM:To compare efficacy of proton pump inhibitors(PPIs)with H2-receptor antagonists(H2RAs)plus prokinetics(Proks)for dysmotility-like symptoms in functional dyspepsia(FD).METHODS:Subjects were randomized to receive openlabel treatment with either rabeprazole 10 mg od(n= 57)or famotidine 10 mg bid plus mosapride 5 mg tid(n=57)for 4 wk.The primary efficacy endpoint was change(%)from baseline in total dysmotility-like dyspepsia symptom score.The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS:The improvement in dysmotility-like dyspep-sia symptom score on day 28 was significantly greater in the rabeprazole group(22.5%±29.2%of baseline) than the famotidine+mosapride group(53.2%± 58.6%of baseline,P<0.0001).The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status.Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine+mosapride group(87.7%vs 59.6%,P= 0.0012).Rabeprazole therapy was the only significant predictor of treatment response(P<0.0001),defined as a total symptom score improvement≥50%.CONCLUSION:PPI monotherapy improves dysmotility-like symptoms significantly better than H2RAs plus Proks,and should be the treatment of first choice for Japanese FD.
基金funded by the National Natural Science Foundation of China(32001941 and 31972303)the China Postdoctoral Science Foundation(2020M683586)the Research Fund for the Doctoral Program of Northwest A&F University(Z1090219195).
文摘Spinosyns,including spinosad and spinetoram,act on the insect central nervous system,gradually paralyzing or destroying the target insect.Spinosad resistance is associated with loss-of-function mutations in the nicotinic acetylcholine receptor(nAChR)α6 subunit in a number of agricultural pests.Using gene editing,nAChRα6 has been verified as a target for spinosyns in five insect species.Recently,a point mutation(G275E)in exon 9 of nAChRα6 was identified in spinosad-resistant strains of Thrips palmi and Tuta absoluta.To date,no in vivo functional evidence has been obtained to support that this mutation is involved in spinosyn resistance in lepidopteran pests.In this study,the G275E mutation was introduced into the nAChR of Spodoptera exigua using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology.Reverse transcriptase-polymerase chain reaction and sequencing confirmed that this mutation was present in exon 9 of the nAChR transcripts in the edited 275E strain.The results of bioassays showed that the 275E strain was highly resistant to spinosad(230-fold)and spinetoram(792-fold)compared to the unedited background strain,directly confirming that the G275E mutation of the nAChRα6 subunit confers high levels of spinosyn resistance in S.exigua.Inheritance analysis showed that the resistance trait is autosomal and incompletely recessive.This study employs a reverse genetics approach to validate the functional role played by the G275E mutation in nAChRα6 of S.exigua in spinosyns resistance and provides another example of the use of CRISPR/Cas9 gene-editing technology to confirm the role played by candidate target site mutations in insecticide resistance.
文摘以自建的英国、美国、印度和新加坡四国英文媒体(以下简称“英美印新英文媒体”)有关“人类命运共同体”的新闻报道语料库为基础,采用基于语料库的批评话语分析方法,分析“人类命运共同体”英译在英美印新英文媒体的传播与接受效果。研究发现,“人类命运共同体”理念在英美印新英文媒体中得到了广泛关注,其最新译名“community with a shared future for mankind”的使用频率愈来愈高,有取代其他译名的趋势。但由于受意识形态偏见和地缘政治等因素的影响,“人类命运共同体”理念在英美印新英文媒体中的接受情况还存在一定差距。为此,建议优化中国特色外交话语国际传播策略,希冀为“人类命运共同体”理念更好地“走出去”贡献力量。
