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1.
Lancet ; 396(10267): 1941, 2021 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-33341126
2.
Sheng Wu Gong Cheng Xue Bao ; 36(10): 2001-2016, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33169566

RESUMO

Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of ß-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and ß-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.


Assuntos
Alcaloides , Enzimas , Pesquisa , Tetra-Hidroisoquinolinas , Alcaloides/química , Catálise , Enzimas/metabolismo , Pesquisa/tendências , Tetra-Hidroisoquinolinas/química
3.
Sheng Wu Gong Cheng Xue Bao ; 36(10): 2029-2039, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33169568

RESUMO

Ischemic stroke is a major health crisis causing high mortality and morbidity. The key treatment relies on the rapid intervention to dissolve thrombus, to reduce bleeding side effect and re-canalize clotted blood vessels using clot lysis drugs. Tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke, but it has many limitations in clinical use. In recent years, the development of thrombolytic drugs and treatment strategies based on tPA has been progressed rapidly. Here we review the recent progress in this field, including the contributions from us and others, to promote the future development of novel thrombolytic drugs.


Assuntos
Isquemia Encefálica , Fibrinolíticos , Acidente Vascular Cerebral , Terapia Trombolítica , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Pesquisa/tendências , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/tendências , Ativador de Plasminogênio Tecidual/uso terapêutico
4.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(5): 542-547, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33185072

RESUMO

Aquaporins (AQPs) are a class of membrane intrinsic proteins in medical helminthes that specifically mediate the transmembrane transport of water or other solute molecules. Previous studies have demonstrated that AQPs play a critical role in promoting the transmembrane transport of water, osmoregulation, uptake of nutrients, release of toxic metabolic products and transport of antiparasitic drugs, which may serve as promising vaccine candidates and drug targets for parasitic diseases. This review describes the structural characteristics of AQPs in medical helminthes, and discusses the feasibility of these AQPs as antihelminth vaccine candidates and drug targets, so as to provide insights into the development of novel vaccines and drugs against parasitic diseases.


Assuntos
Aquaporinas , Helmintíase , Helmintos , Animais , Aquaporinas/metabolismo , Transporte Biológico , Helmintíase/parasitologia , Helmintíase/prevenção & controle , Helmintos/fisiologia , Humanos , Proteínas de Membrana/metabolismo , Pesquisa/tendências , Água/metabolismo
5.
BMC Womens Health ; 20(1): 249, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172466

RESUMO

COVID-19 related guidelines and movement restrictions are designed to protect the public's health and reduce disease transmission; yet, COVID-19 related restrictions on movement including social distancing, isolation, quarantine, and shelter-in-place orders have an unknown effect on violence and abuse within relationships. As the pandemic has progressed, many have justifiably speculated that such restrictions may pose a danger to the safety and well-being of people experiencing such violence. Early in the pandemic, countries hard hit by COVID-19 began raising the alarm bell about the impacts of the disease on IPV occurrence. Police in China report that 90% of the causes of recent IPV cases could be attributed to the COVID-19 epidemic. Rising fears and anxiety about prolonged movement restrictions, increased economic strain and diminished health care capacity to support survivors are among the potential reasons for such dramatic effects. Under normal circumstances: low income, unemployment, economic stress, depression, emotional insecurity and social isolation are all risk factors for using violence against partners. Many of these factors may worsen in the context of COVID-19. Despite the urgency in addressing COVID-19, existing health concerns like Intimate Partner Violence (IPV) persist-and may well be worsened by the virus. We simply do not yet know the effects of COVID-19 on violence, nor do we know which interventions work best to prevent and respond to it within the context of the pandemic. The vast majority of information available about IPV and violence during the pandemic has been based on anecdotal reports. The call to action for the research community is clear. We must systematically measure the effects of COVID-19 and movement related restrictions on violence. As always when researching violence, serious consideration must be given to ethics and safety. Violence researchers must mobilize to investigate the impacts of COVID-19 on violence and human health.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Violência por Parceiro Íntimo , Pandemias , Pneumonia Viral , China , Humanos , Pesquisa/tendências
6.
PLoS One ; 15(11): e0242468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33196668

RESUMO

Science is becoming increasingly international in terms of breaking down walls in its pursuit of high impact. Despite geographical location and distance still being major barriers for scientific collaboration, little is known about whether high-impact collaborations are similarly constrained by geography compared to collaborations of average impact. To address this question, we analyze Web of Science (WoS) data on international collaboration between global leader cities in science production. We report an increasing intensity of international city-city collaboration and find that average distance of collaboration of the strongest connections has slightly increased, but distance decay has remained stable over the last three decades. However, high-impact collaborations span large distances by following similar distance decay. This finding suggests that a larger geographical reach of research collaboration should be aimed for to support high-impact science. The creation of the European Research Area (ERA) represents an effective action that has deepened intracontinental research collaborations and the position of the European Union (EU) in global science. Yet, our results provide new evidence that global scientific leaders are not sufficiently collaborative in carrying out their big science projects.


Assuntos
Pesquisa Interdisciplinar/tendências , Pesquisa/tendências , Cidades/estatística & dados numéricos , Comportamento Cooperativo , União Europeia , Geografia , Humanos , Cooperação Internacional , Colaboração Intersetorial , Liderança , Comportamento Social
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 644-650, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33210494

RESUMO

A large number of viruses have been found to be associated with ocular diseases, including human adenovirus, human herpesvirus (HHV), human T lymphotropic virus type-1 (HTLV-1), and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This group of diseases is prone to be misdiagnosed or missed diagnosis, resulting in serious tissue and visual damage. Etiological diagnosis is a powerful auxiliary mean to diagnose the ocular diseases associated with human adenovirus, herpes simplex virus 1 and varicella-zoster virus, and it provides the leading diagnosis evidence of infections with herpes simplex virus 2, Epstein-Barr virus, cytomegalovirus, HHV-6/7, HHV-8, HTLV-1 and SARS-CoV-2. Virus isolation, immunoassay and genetic diagnosis are usually used for etiologic diagnosis. For genetic diagnosis, the PCR technique is the most important approach because of its advantages of rapid detection, convenient operation, high sensitivity and high specificity.


Assuntos
Oftalmopatias , Pesquisa , Viroses , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , DNA Viral/genética , Oftalmopatias/diagnóstico , Oftalmopatias/virologia , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pesquisa/tendências , Viroses/diagnóstico , Viroses/virologia
8.
Yi Chuan ; 42(11): 1042-1061, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229312

RESUMO

Since Takahashi and Yamanaka reported the generation of induced pluripotent stem cells (iPSCs) in 2006, the field of pluripotent stem cells has entered an unprecedented state of development. It plays an important role in disease modeling, drug discovery and cell therapy, and promotes the development of cell biology and regenerative medicine. At present, iPSC technology has become an important tool for studying of pathological mechanisms. New drugs screened by iPSC technology are being developed, and the number of clinical trials using iPSC-derived cells is gradually increasing. The latest research progress of iPSCs, combined with gene editing technology and 3D organoid methodology, promotes the further applications of iPSCs in disease research. In this review, we introduce the innovation of reprogramming methods in recent years, analyze the advantages and disadvantages of four reprogramming methods: integrated virus vector system, integrated non-viral vector system, non-integrated virus vector system and non-integrated non virus vector system. At the same time, we summarize the latest research progress on iPSCs in disease modeling and clinical treatment strategies, so as to provide a reference for further in-depth research in various fields of iPSCs.


Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Edição de Genes , Humanos , Medicina Regenerativa/tendências , Pesquisa/tendências
9.
Yi Chuan ; 42(11): 1073-1080, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229314

RESUMO

As an important biological technology, stem cell technology has been being widely used in the life sciences for a long time. There are three major ways to obtain stem cells with unlimited proliferation and differentiation capabilities, including 1) isolating embryonic stem cells (ESCs) from embryos, 2) isolating adult stem cells from adult tissues, and 3) in vitro reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs). In the field of agriculture, the efficient purification, culture and establishment of livestock and poultry stem cell lines are expected to significantly improve the efficiency of somatic cell cloning and genetic modification of cells. The technology of stem cell induced-gamete production will greatly simplify the generation process, and consequently improve the generation efficiency of genetically modified animals. In addition, by combining with gene editing, microinjection, stem cell transplantation, and embryo transfer, stem cell technology has great potential in the production of genetically modified animals, tissue and organ donors, in vitro induced gametes and genetically reconstructed embryos, in the screening of disease treatment targets, and in the research of new drug pharmacology, which is of great significance to the genetic improvement, disease prevention and treatment for agricultural animals. In this review, we summarize the current research progress of stem cells in agricultural animals, including pig (Sus scrofa), cattle (Bos taurus), chicken (Gallus gallus), goat (Capra hircus) and sheep (Ovis aries), to provide information for the studies in the field of stem cells in agricultural animals.


Assuntos
Gado , Células-Tronco Pluripotentes , Pesquisa , Animais , Bovinos , Linhagem Celular , Pesquisa/tendências , Ovinos , Suínos
10.
Yi Chuan ; 42(10): 929-948, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229320

RESUMO

Knowledge of the origin of eukaryotes is key to broadening our understanding of the eukaryotic genome and the relationship among internal structures within a eukaryotic cell. Since the discovery of archaea in 1977 and the proposal of three-domain tree of life by the American microbiologist Carl Woese, the intimate relationship in evolution between eukaryotes and archaea has been demonstrated by considerable experiments and analyses. From the beginning of the 21st century, with the development of phylogenetic methods and the discovery of new archaeal phyla more related to eukaryotes, increasing evidence has shown that Eukarya and Archaea should be merged into one domain, leading to a two-domain tree of life. Nowadays, the Asgard superphylum discovered via metagenomic analysis is regarded as the closest prokaryotes to eukaryotes. Nevertheless, several key questions are still under debate, such as what the ancestors of the eukaryotes were and when mitochondria emerged. Here, we review the current research progress regarding the changes of the tree of life and the detailed eukaryotic evolutionary mechanism. We show that the recent findings have greatly improved our knowledge on the origin of eukaryotes, which will pave the way for future studies.


Assuntos
Evolução Biológica , Eucariotos , Archaea/classificação , Archaea/genética , Eucariotos/classificação , Eucariotos/genética , Pesquisa/tendências
11.
Yi Chuan ; 42(10): 949-964, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229321

RESUMO

Thalassemia and hemophilia are common inherited blood disorders caused by genetic abnormalities. These diseases are difficult to cure and can be inherited to the next generation, causing severe family and social burden. The emergence of gene therapy provides a new treatment for genetic diseases. However, since its first clinical trial in 1990, the development of gene therapy has not been as optimistic in the past three decades as one could hope. The development of gene-editing technology, particularly the third generation gene-editing technology CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9), has given hope in such therapeutic approach for having advantages in high editing efficiency, simple operation, and low cost. Gene editing-mediated gene therapy has thus received increasing attention from the biomedical community. It has shown promises for the treatment of inherited blood disorders, such as thalassemia and hemophilia. This paper reviews the fundamental research progress of gene therapy for ß-thalassemia and hemophilia based on CRISPR/Cas9 technology in the past six years. It also summarizes the CRISPR/Cas9-based clinical trials of gene therapy. The problems and possible solutions to this technology for gene therapy are also discussed, thereby providing a reference for the research on gene therapy of inherited blood disorders based on CRISPR/Cas9 technology.


Assuntos
Terapia Genética , Hemofilia A , Talassemia beta , Sistemas CRISPR-Cas/genética , Ensaios Clínicos como Assunto , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Pesquisa/tendências , Tecnologia , Talassemia beta/genética , Talassemia beta/terapia
12.
Yi Chuan ; 42(10): 965-978, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229322

RESUMO

Elevated serum level of low density lipoprotein cholesterol (LDL-C) is the leading risk factor for cardiovascular disease. LDL receptor (LDLR)-mediated LDL clearance is the major factor determining the LDL-C level in the circulation. LDL binds to the LDLR on the cell surface and enters the cells through classical clathrin-coated vesicles. In the acidic endosome, LDLR is uncoupled from LDL and recycles back to the cell surface. The released LDL is transported to the lysosome for degradation. The proprotein convertase subtilisin kexin type 9 (PCSK9) gene encodes a hepatic secretory protein, and its mutations are strongly associated with levels of LDL-C. We and others have shown that PCSK9 directly interacts with LDLR on the cell surface and both are internalized through the clathrin-coated vesicles. However, in the acidic endosome, PCSK9 and LDLR form a tight complex and are targeted to lysosome for degradation, thereby reducing the level of LDLR on the surface of hepatocytes and decreasing hepatic clearance of LDL-C, which plays an important role in maintaining a relatively constant level of LDL in the plasma. Thus, blocking PCSK9 function has become a new strategy to treat hypercholesterolemia.In this review, we will summarize the latest progress in the functional and mechanistic studies of PCSK9 and also highlight the research progress of PCSK9 inhibitors. It aims to provide a reference for the study of PCSK9-LDLR pathway and the regulation of cholesterol metabolism.


Assuntos
Pró-Proteína Convertase 9 , Receptores de LDL , Hepatócitos/enzimologia , Humanos , Lipossomos/metabolismo , Mutação , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/metabolismo , Pesquisa/tendências
13.
Yi Chuan ; 42(10): 979-992, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229323

RESUMO

Bone is a hard organ that makes up vertebrate endoskeleton, which plays a role in movement, support and protection for the body. The normal growth and development of bone is in the dynamic balance of bone metabolism, which is composed of bone formation and bone absorption. This balance is very important for maintaining bone mass and mineral homeostasis. In the process of bone growth and metabolism, there are many signaling pathways regulating bone formation and absorption, such as BMP (bone morphogenetic protein)/SMADs, TGF-ß (transforming growth factor ß), Wnt/ß-catenin, OPG (osteoprotegerin)/RANKL (receptor activator of NF-κB ligand)/RANK (receptor activator of NF-κB), FGF (fibroblast growth factor) and Notch signaling pathway. These signaling pathways have complex regulatory mechanisms and are involved in the regulation of bone metabolism. In this review, we summarize the mechanism and research progress of signal pathways that play key regulatory roles in the process of animal bone metabolism, thereby laying a foundation for research in animal bone metabolism.


Assuntos
Osso e Ossos , NF-kappa B , Transdução de Sinais , Animais , Osso e Ossos/metabolismo , NF-kappa B/metabolismo , Pesquisa/tendências
14.
Yi Chuan ; 42(10): 993-1003, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229324

RESUMO

Cloning, also known as somatic cell nuclear transfer (SCNT), is an asexual reproduction technique that reprograms differentiated cells to the totipotent state, and generates offspring with a genotype identical to the donor cells. Pig cloning technique holds great promise for propagating excellent breeding boars, generating genetically modified pigs, protecting rare and endangered pigs and studying the mechanisms of somatic cell nucleus reprogramming. However, cloned pigs suffer from various developmental defects, including low birth rate, low birth weight, and high stillbirth occurrence, neonatal mortality and congenital malformations, which severely hamper their applications. Errors in epigenetic reprogramming of donor nucleus are considered as the main causes of low cloning efficiency and abnormal embryonic development in cloned embryos and animals. However, most studies to correct the errors in epigenetic reprogramming of cloned pig embryos have not substantially improved the birth and survival rates of cloned pigs. In this review, we summarize the abnormal phenotypes, causes of abnormal development of cloned pigs and effective methods for improving pig cloning efficiency, thereby providing a reference for the future research to improve the development and survival rates of cloned pig embryos and cloned pigs.


Assuntos
Clonagem de Organismos , Técnicas de Transferência Nuclear , Animais , Diferenciação Celular , Clonagem de Organismos/normas , Desenvolvimento Embrionário , Epigênese Genética , Feminino , Gravidez , Pesquisa/tendências , Suínos/genética
15.
Rinsho Shinkeigaku ; 60(11): 743-751, 2020 Nov 27.
Artigo em Japonês | MEDLINE | ID: mdl-33115998

RESUMO

Cerebral small vessel disease (SVD) is defined as difficulty maintaining efficient microcirculation, metabolism, and neural networks caused by degeneration of small vessels of the brain, as well as cognitive or physical dysfunction caused by this difficulty. The most common SVD (i.e., type 1 SVD), which is driven by hypertensive arteriopathy, appears to be more prevalent in people with East Asian ethnicity than in Whites. Recent attention has been paid to a SVD scoring system using major MRI markers of SVD in an attempt to comprehensively semi-quantify the SVD burden in the brain. This concept raised a new question: "Is there a practical threshold for the comprehensive SVD score?" The development of computational methods to assess SVD imaging markers could answer this question, and may help identify the optimal intervention for patients with type 1 SVD to prevent stroke and dementia.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Pesquisa/tendências , Animais , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/etiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/prevenção & controle , Disfunção Cognitiva , Grupos de Populações Continentais , Desenvolvimento de Medicamentos/tendências , Humanos , Imagem por Ressonância Magnética , Camundongos , Acidente Vascular Cerebral
16.
Zhonghua Yi Xue Za Zhi ; 100(38): 2961-2965, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33086447
18.
J Neurointerv Surg ; 12(11): 1049-1052, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32998982

RESUMO

BACKGROUND: Academic physicians aim to provide clinical and surgical care to their patients while actively contributing to a growing body of scientific literature. The coronavirus disease 2019 (COVID-19) pandemic has resulted in procedural-based specialties across the United States witnessing a sharp decline in their clinical volume and surgical cases. OBJECTIVE: To assess the impact of COVID-19 on neurosurgical, stroke neurology, and neurointerventional academic productivity. METHODS: The study compared the neurosurgical, stroke neurology, and neurointerventional academic output during the pandemic lockdown with the same time period in previous years. Editors from a sample of neurosurgical, stroke neurology, and neurointerventional journals provided the total number of original manuscript submissions, broken down by months, from the year 2016 to 2020. Manuscript submission was used as a surrogate metric for academic productivity. RESULTS: 8 journals were represented. The aggregated data from all eight journals as a whole showed that a combined average increase of 42.3% was observed on original submissions for 2020. As the average yearly percent increase using the 2016-2019 data for each journal exhibited a combined average increase of 11.2%, the rise in the yearly increase for 2020 in comparison was nearly fourfold. For the same journals in the same time period, the average percent of COVID-19 related publications from January to June of 2020 was 6.87%. CONCLUSION: There was a momentous increase in the number of original submissions for the year 2020, and its effects were uniformly experienced across all of our represented journals.


Assuntos
Infecções por Coronavirus , Eficiência , Neurologia/estatística & dados numéricos , Neurocirurgia/estatística & dados numéricos , Pandemias , Pneumonia Viral , Pesquisa/estatística & dados numéricos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/cirurgia , Universidades/estatística & dados numéricos , Humanos , Neurocirurgia/tendências , Publicações Periódicas como Assunto , Editoração , Quarentena/estatística & dados numéricos , Pesquisa/tendências , Universidades/tendências
20.
Yakugaku Zasshi ; 140(9): 1107-1117, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879243

RESUMO

The true central aim of pharmaceutical research and education is to strive for the patient's satisfaction, i.e., "for the sake of the patient". Our research focuses to bridge the gap between the ideal and current situation in pharmaceutical science. We also investigated/questioned the united roles of pharmacists and pharmacies, with the ambition of changing the work culture of pharmacists. This paper reviews the history of our research and discusses the future of pharmaceutical research and education.


Assuntos
Biofarmácia/educação , Educação em Farmácia/tendências , Pesquisa/tendências , Análise de Dados , Humanos , Satisfação do Paciente , Farmacêuticos , Farmácia
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