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Resumo Este artigo procurou contribuir para a literatura e para o debate nacional e global sobre a superação de uma polarização relacionada ao aspecto jurídico e administrativo do processo de inovação, procurando se concentrar nas patentes como um fator condicionante das trajetórias tecnológicas que viabilizam o aprendizado em âmbito produtivo. Baseou-se em um arcabouço teórico e político relacionado à inovação e ao acesso a medicamentos, especialmente quanto aos direitos de Propriedade Intelectual, e na análise crítico-reflexiva de instrumentos de Propriedade Intelectual utilizados em Parcerias para o Desenvolvimento Produtivo (PDP), desenvolvidas por um instituto de tecnologia em fármacos sintéticos, público e nacional. Os resultados demonstram a relevância da compatibilização dos direitos de patentes com a construção de uma capacidade tecnológica e de inovação no país, vinculada ao acesso universal, especialmente quando envolverem produtos que se destinam ao tratamento de doenças graves, de alta complexidade tecnológica e de alto custo. Conclui-se que, para superação da dependência tecnológica e ampliação do acesso a medicamentos no Brasil, o Estado deve buscar o equilíbrio entre os interesses públicos e privados na área da saúde, a articulação entre os instrumentos jurídicos legais existentes e o alinhamento entre suas políticas de saúde, industriais, de CT&I e Propriedade intelectual.
Abstract This article aims to contribute to the literature and to the national and global debate on overcoming the polarization related to the legal and administrative aspect of the innovation process, seeking to focus on patents as a conditioning factor of the technological trajectories that enable learning in the productive scope. It was based on a theoretical and political framework related to innovation and access to medicines, especially regarding Intellectual Property rights, and on a critical-reflexive analysis of Intellectual Property instruments used in Productive Development Partnerships (PDP), developed by a public national institute for synthetic drug technology. The results demonstrate the importance of making patent rights compatible with the construction of technological and innovation capacities in the country, which are linked to universal access, especially when they involve products that are intended to treat serious, technologically complex and high-cost diseases. In conclusion, to overcome technological dependence and expand access to medicines in Brazil, the State must seek a balance between public and private interests in the healthcare area, articulate the existing legal instruments and align its health, industry, ST&I and intellectual property policies.
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Resumo A covid-19 jogou luz sobre o impacto negativo da propriedade intelectual na saúde e deu nova relevância à Ação Direta de Inconstitucionalidade 5529/DF, que, acatada pelo Supremo Tribunal Federal em 2021, culminou na extinção da extensão automática de patentes no Brasil. Este estudo busca analisar o efeito do julgamento histórico da ADI 5529/DF sobre pedidos de patente e as patentes de interesse das Parcerias para Desenvolvimento Produtivo (PDP). Trata-se de um estudo com base em uma pesquisa documental de análise do andamento, até 31 de dezembro de 2020, de 90 pedidos de patente relacionados a 15 medicamentos objetos de PDP. Nos sites do Instituto Nacional de Propriedade Industrial, do Ministério da Saúde, da Anvisa e da Câmara de Regulação do Mercado de Medicamentos, foram pesquisadas variáveis para comparar o cenário patentário dos medicamentos com o das PDP. De 88 pedidos válidos, 28 patentes foram concedidas, das quais dezessete foram estendidas para mais de vinte anos (média de 24 anos e nove meses). A decisão do STF resultou em mais de 68 anos de monopólio perdidos, potencialmente desanuviando alternativas para a produção de genéricos no país. Neste momento de retomada das PDP, estratégias para a superação de barreiras patentárias deveriam ser incorporadas à política.
Abstract The COVID-19 pandemic has shed light on the negative impact of intellectual property on health and has given new relevance to the Direct Action of Unconstitutionality 5529/DF, which was ruled by the Supreme Court in 2021, resulting in the extinction of automatic patent extensions in Brazil. This documentary case study analyzes the effects of the judicial decision on patent applications and patents of interest for Productive Development Partnerships (PDP), investigating the progress of 90 patent applications related to 15 PDPs drugs of interest until Decembre 31, 2020. Variables for comparing the drug patent scenario with that of the PDPs were researched on the websites of the National Institute of Industrial Property, the Ministry of Health, ANVISA, and the Brazilian Medicines Market Regulation Chamber. Of 88 valid applications, 28 patents were granted, 17 of which had been extended to more than 20 years (24 years and 09 months average). The court decision resulted in a loss of over 68 years of monopoly, potentially opening alternatives for generic production. This resumption of the PDP policy should incorporate strategies to overcome patent barriers.
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In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.
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ObjectiveTo investigate the functions and characteristics of traditional Chinese medicine （TCM） from plant skin and their Chinese patent medicines and explore the related laws of the medicinal tissue， property， taste， efficacy， and clinical application， so as to strengthen the theory of identifying symptoms for qualities and provide references for the development and utilization of TCM from plant skin and their Chinese patent medicines. MethodBy reviewing the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias， TCM from plant skin and their Chinese patent medicines were screened out， and the characteristics， functions， and precautions of TCM from plant skin and their Chinese patent medicines were summarized. Statistical analysis was carried out with Excel. ResultA total of 62 TCM from plant skin were found， mainly distributed in one kingdom， three phyla， and 31 families. In terms of the family genus， Rutaceae>Leguminosae>Cucurbitaceae. In terms of the medicinal tissue， bark>root bark>fruit bark>seed bark. In terms of property and taste， warm>cold>plain>cool>hot， and bitter>sweet=pungent>acidic. In terms of meridians， lung>liver>spleen>heart>colorectal>kidney>stomach=bladder. In terms of TCM classification， most of them belong to the category of heat-clearing medicines. There were 485 types of Chinese patent medicines from plant skin， with the most Chinese patent medicines containing Citri Reticulatae Pericarpium. Among the forms of administration， pills were the most predominant. In terms of the tastes of the medicines， bitter and sweet flavors predominated. In terms of functions， medicines for strengthening the body resistance were the most. For the precautions， contraindications during pregnancy were the most common. ConclusionThere is a correlation among medicinal tissue， property， taste， efficacy， and clinical application of TCM from plant skin. It is also necessary to pay attention to the contraindications of the medicines and rationally choose TCM from plant skin and their Chinese patent medicines under the guidance of TCM theory based on syndrome differentiation and treatment.
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OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.
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The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.
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Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.
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Animals , Rabbits , Copper/pharmacology , Tissue Scaffolds/chemistry , Bone Regeneration , Anti-Bacterial Agents/pharmacology , Osteogenesis , Calcium , Ions/pharmacologyABSTRACT
The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present， and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this， this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research， analyzes the protection forms applicable to intellectual property of Chinese materia medica， such as patents， administrative protection， trademarks， designs and intangible cultural heritages， and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions：①paying attention to patent applications for planting/processing methods of raw medicinal materials， ②emphasizing the protection of geographical indications， authentic medicinal herbs， and new plant varieties， ③actively promoting product and technology upgrades， ④applying for data protection during product iteration， ⑤emphasizing the layout timing of patent and administrative protection， ⑥focusing on improving goodwill， ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry， academia， and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case， and optimize the strategy to better protect related products.
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Trolling with new technologies is a disruptive, deceptive, and destructive behavior, with great psychosocial, legal, and economical relevance. However, there are no studies in the scientific literature that have examined the properties of questionnaires to assess them. Therefore, the purpose of the present study was to observe the psychometric properties of the Revised Trolling Questionnaire by Buckels et al.'s in a sample of Argentinean adults. An intentional sample of 837 participants from Argentina (mean age = 28.4 years; 61% female) was formed. They completed the Buckels et al.'s Revised Trolling Questionnaire, measures of dark personality, Internet addiction, cyberstalking, and socio-demographic questions. Exploratory and confirmatory factorial analyses indicated a one-factor structure with correct fit statistics. Internal consistency was adequate: Cronbach's α = .80 and Omega coefficient (ω) = .81. Concurrent validity of the trolling questionnaire was observed with dark personality (Machiavellianism, narcissism and psychopathy), problematic Internet use (symptomatology and disfunctionality), and cyberstalking. Machiavellianism and disfunctionality were the most significant variables associated with trolling. Therefore, the Argentinean Spanish version of this test showed evidence of adequate psychometric properties.
El trolling mediante las nuevas tecnologías es un comportamiento disruptivo, molesto y destructivo, con una gran relevancia psicosocial, legal y jurídica. No existen estudios en la literatura científica que hayan examinado las propiedades de un instrumento para evaluarlo. El propósito del presente estudio fue observar las propiedades del Cuestionario Revisado de Trolling de Buckels et al. en una muestra de adultos argentinos. Se constituyó una muestra intencional de 837 participantes argentinos (edad promedio=28,4 años; 61% mujeres). Completaron el Cuestionario Revisado de Trolling de Buckels et al., un cuestionario de personalidad oscura (maquiavelismo, psicopatía y narcicismo), de adicción a internet, de cyberstalking y preguntas sociodemográficas. Un análisis factorial exploratorio como confirmatorio indicó una correcta estructura unifactorial. La consistencia interna fue adecuada: α de Cronbach = .80 y Omega coefficient (ω) = .81. La validez concurrente del cuestionario se observó con el cyberstalking, la personalidad oscura (maquiavelismo, narcisismo y psicopatía) y el uso problemático de Internet. El maquiavelismo y la disfuncionalidad eran las variables más asociadas al trolling. De este modo, la versión al español argentino de dicho test mostró evidencia de adecuadas propiedades psicométricas.
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RE S U M E N Si bien los lineamientos vigentes para el Ordenamiento Social de la Propiedad Rural-OSPR establecen, entre otros criterios, la transversalización del enfoque diferencial y la verificación de presencia de comunidades étnicas, no se reconoce expresamente el derecho a la tierra del campesinado. Partiendo de las perspectivas teóricas del Estructuralismo Agrario y del Enfoque Socio-Territorial, este trabajo busca proponer lineamientos complementarios para adelantar un proceso de Ordenamiento Social de la Propiedad Rural OSPR que reconozca este derecho, en los corregimientos que actualmente están siendo propuestos para la constitución de una Zona de Reserva Campesina (ZRC) en Pradera, Valle del Cauca. Para tal fin, se hace un acercamiento a la dinámica histórica del poblamiento y apropiación de la tierra por parte del campesinado y se geoespacializan dentro del polígono de la ZRC los predios por rango de tamaño, las coberturas y fertilidad del suelo y la zonificación de la Reserva Forestal, con los cuales se evidencia la existencia de una territorialidad campesina, la necesidad de redistribuir la tierra, de sustraer áreas de la reserva forestal y de acelerar la constitución de la Zona de Reserva Campesina (ZRC).
Embora as diretrizes atuais para a Ordenação Social da Propriedade Rural-OSPR estabeleçam, entre outros critérios, a integração da abordagem diferencial e a verificação da presença de comunidades étnicas, o direito à terra do campesinato não é expressamente reconhecido. Baseado nas perspectivas teóricas do Estruturalismo Agrário e da Abordagem Sócio-Territorial, este documento procura propor diretrizes complementares para avançar um processo de OSPR que reconheça este direito nos municípios que estão sendo propostos atualmente para a constituição de uma Zona de Reserva Camponesa (ZRC) em Pradera, Valle del Cauca. Para este fim, é feita uma abordagem da dinâmica histórica do assentamento e apropriação da terra pelo campesinato e a geo-espatização dentro do polígono da ZRC das propriedades por faixa de tamanho, cobertura e fertilidade do solo e o zoneamento da Reserva Florestal, que mostra a existência de uma territorialidade camponesa, a necessidade de redistribuir a terra, de subtrair áreas da reserva florestal e de acelerar a constituição da ZRC.
A B S T R A C T Although the current guidelines for the Social Planning of Rural Property (OSPR, acronym in Spanish) establish, among other criteria, the mainstreaming of a differential perspective and the inclusion of ethnic communities, land-rights for peasants are not expressly recognized. Drawing from the theoretical perspectives of Agrarian Structuralism and the Socio-Territorial Approach, this paper proposes complementary guidelines to support an OSPR process that recognizes this right, in the districts that are currently being projected for the constitution of a Peasant Reserve Zone (ZRC, acronym in Spanish) in Pradera, Valle del Cauca. To this end, we describe the historical dynamics of the settlement and appropriation of the land by the peasantry and, within the ZRC polygon, we geospatiolize the properties by range of size, soil coverage and fertility and the zoning of the Forest Reserve, through which we provide evidence for the existence of a peasant territoriality, the need to redistribute land, to subtract areas of the Forest Reserve and to accelerate the constitution of the ZRC.
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Understanding the mechanism of information processing in plants remains a challenging task even in the era of machine learning and artificial neural networks. Sir J.C. Bose had demonstrated through his experiments that the various modes of stimulation which effectively initiated nervous impulse in animals led to impulse generation in the excitable plant Mimosa pudica as well. In order to localize the tissue responsible for conduction of excitation in the petiole of Mimosa, Bose had constructed a specialized ‘Electric Probe’ (glass tip electrode). From this experiment, Bose found that there were different intensities of transmitted excitation in different tissue layers of the petiole. In this backdrop, an experimental research has been conducted to comparatively study the pattern of spatial voltage distribution across different tissue layers in both, a non-excitable plant Alternanthera philoxeroides (in stem) and an excitable plant Mimosa pudica (in petiole), by following experimental principles similar to that of Sir J. C. Bose. For the present experimental study, the electrical probes (glass tip electrode), similar to the one designed by J.C. Bose and the whole experimental setup has been constructed and developed completely in the laboratory. The results indicated a striking difference in the spatial voltage distribution pattern between the non-excitable and the excitable plant. Since Mimosa is an excitable plant having specialized mechanoreceptor cells, the change in spatial voltage distribution in the different layers of petiole, following excitation (uniform electrical stimuli) of a sub-petiole has been also studied, as an additional segment of the present research. In the present study a notable difference in the intensities of the transmitted excitation was also found upon electrical stimulation of one of the sub-petioles of the excitable plant M. pudica.
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O presente artigo apresenta resultados de uma pesquisa bibliográfica que teve como objetivo realizar uma reflexão crítica sobre a relação entre a questão ambiental e a discussão internacional sobre sustentabilidade, evidenciando, a partir de acordos multilaterais da globalização econômica, a geopolítica internacional de interesses contraditórios defendidos no âmbito da Convenção sobre a Diversidade Biológica (CDB) e o Acordo sobre Aspectos Comerciais Relativos aos Direitos de Propriedade Intelectual (Agreement on Trade-Related Aspects of Intellectual Property Rights TRIPS), estabelecido pela Organização Mundial do Comércio (OMC). Entre os principais resultados, aponta-se que os princípios de proteção da natureza e dos conhecimentos das populações tradicionais estabelecidos na CDB estão em confronto com os interesses do sistema internacional de propriedade intelectual na arena de disputa pelo acesso aos recursos da natureza e ao conhecimento das populações tradicionais pela indústria mundial de biotecnologia
This article presents the results of a bibliographical research, which aimed tocarry out a critical reflection on the relationship between the environ-mental issue and the international discussion on sustainability, highlighting, from multilateral agreements on economic globalization, the international geopolitics of contradictory interests defended within the scope of the Convention on Biological Diversity (CBD) and the intellectual property agreement (TRIPS) established by the World Trade Organization (WTO). Among the main results, it is pointed out that the principles of protecting nature and the knowledge of traditional populations established in the CBD are in conflict with the interests of the international intellectual property system, through the dispute for access to natural resources and knowledge of traditional populations by the global biotechnology industry
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EnvironmentABSTRACT
Abstract Background Researchers have demonstrated that various measurement concepts and dimensions depend on context and timing. Objectives The current study aimed to determine the psychometric properties of the Javanese couples' marital quality scale based on validity and reliability Methods In total 840 participants or 420 marital dyad from Java, Indonesia, were involved in this study. The psychometrics properties scale was analyzed using exploratory and confirmatory factor analysis, convergent and discriminant analysis, and composite reliability. Results The exploratory factor analysis found relationship quality to consist of support, physical proximity, warmth, communication, acceptance and respect, role sharing, and responsibility factors. Well-being quality consists of happiness, harmony, and problem-solving. The fit of the measurement model was obtained using confirmatory factor analysis. The fit model was also found in the husband's and wife's groups, with no differences between them. The high correlations between wife-husband factors also proved the validity based on convergent and discriminant evidence. The reliability coefficient was high for each dimension and construct. Discussion This analysis shows that the marital quality scale developed has information on psychometric properties that can be useful for researchers and the practicians using the marital quality instrument of Javanese couples in particular.
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Objetivo: identificar los usos de plantas medicinales en el contexto de la COVID-19 de acuerdo a creencias y prácticas culturales de pobladores de la Sierra y Selva Central del Perú. Métodos: investigación observacional, transversal, con enfoque cuantitativo. Se consideró el muestreo no probabilístico de 595 sujetos voluntarios (pobladores), quienes respondieron un cuestionario debidamente validado y con fiabilidad. Las hipótesis fueron contrastadas con probabilidad de éxito = 1/10, al 95 % de confianza estadística. Resultados: los resultados indican que en los momentos más críticos de la pandemia COVID-19, los pobladores de la Sierra y Selva Central del Perú usaron plantas medicinales (eucalipto, jengibre, ajo, matico, limón, cebolla, manzanilla y borrajas) para prevenir y tratar los síntomas ocasionados por el SARS-CoV-2, a consecuencia de las creencias y las prácticas culturales que tienen sobre los efectos deseados de sus propiedades antiinflamatorias y descongestionantes, expectorantes, antitusígenas y antivirales. Conclusiones: las plantas medicinales, como el eucalipto, jengibre, ajo, mático, limón, la cebolla, manzanilla y borrajas, fueron las más utilizadas como alternativa en la prevención y tratamiento de síntomas de la COVID-19.
Objective: identify the uses of medicinal plants in the context of COVID-19 according to beliefs and cultural knowledge of inhabitants of the Sierra and Central Jungle of Peru. Methods: observational, cross-sectional research, with a quantitative approach. The nonprobabilistic sampling of 595 voluntary subjects (residents), who answered a duly validated and reliable questionnaire, was considered. The hypotheses were contrasted with probability of success = 1/10, at 95% statistical confidence. Results: the results indicate that in the most critical moments of the COVID-19 pandemic, the inhabitants of the Sierra and Central Selva of Peru used medicinal plants (eucalyptus, ginger, garlic, matico, lemon, onion, chamomile and borage) to prevent and treat the symptoms caused by SARS-CoV-2, as a result of cultural beliefs and knowledge about the desired effects of its anti-inflammatory and decongestant, expectorant, antitussive, and antiviral properties. Conclusions: medicinal plants, such as eucalyptus, ginger, garlic, matico, lemon, onion, chamomile and borage, were the most used as an alternative in the prevention and treatment of symptoms of COVID-19.
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Buscando compreender como as epidemias de zika e chikungunya incitaram o desenvolvimento tecnológico, este estudo realizou levantamento de dados epidemiológicos e prospecção tecnológica, utilizando dados do Instituto Nacional da Propriedade Industrial (INPI) e do Orbit Intelligence. Ainda, analisou produtos desenvolvidos e em desenvolvimento a nível mundial e aqueles registrados no Brasil por meio da Agência Nacional de Vigilância Sanitária (Anvisa). No ano de 2016, observou-se o maior número de casos totais para ambas as doenças. A prospecção tecnológica nacional revelou que há interesse global em desenvolver tecnologias para essas doenças e depositar suas patentes no Brasil, tendo as empresas como principais depositantes. Por sua vez, a prospecção tecnológica global mostrou que o ano de 2016 configura-se como importante marco na evolução do número de patentes para zika e chikungunya, sugerindo que as epidemias brasileiras estimularam o mundo no desenvolvimento de novos insumos para a saúde. Os Estados Unidos e a China são as principais jurisdições, tendo as universidades como maiores depositantes. A análise de produtos a nível global revelou que apenas dois chegaram ao mercado para zika e um para chikungunya, e as vacinas estão na categoria principal. A busca na Anvisa revelou que há mais produtos registrados para zika do que em comparação à chikungunya. Os principais fabricantes legais são empresas brasileiras, com pedidos de registro realizados principalmente pelas empresas DiaSorin S.p.A., ECO Diagnóstica Ltda. e Chembio Diagnostics Brazil Ltda. Apesar do visível estímulo à pesquisa, desenvolvimento e patenteamento gerado pelas epidemias de zika e chikungunya no Brasil, isso não garantiu a chegada de novos produtos ao mercado nem acesso da população a eles.
This study aims to understand how the zika and chikungunya epidemics incited technological development. We surveyed epidemiological data and technological prospecting, using data from Brazilian National Institute of Industry Property (INPI) and Orbit Intelligence, and analyzed products developed/under development worldwide and products registered in Brazil by Brazilian Health Regulatory Agency (Anvisa). In 2016, the highest number of total cases was observed for both diseases. Brazil's technological prospection revealed the existence of a global interest in developing technologies for these diseases and filing their patents in Brazil, with companies as the main depositors. Global technological prospecting showed that 2016 is an important milestone in the evolution of the number of patents for zika and chikungunya, suggesting that Brazilian epidemics stimulated the world in the development of new health inputs. The United States and China are the main jurisdictions, with universities as the largest depositors. Global product analysis revealed that only two products reached the market for zika and one for chikungunya, and vaccines are in the top category. A research in Anvisa revealed more products registered for zika compared to chikungunya. The main legal manufacturers are Brazilian companies, with DiaSorin S.p.A., Eco Diagnóstica Ltda., and Chembio Diagnostics Brazil Ltda. leading the registration requests. Despite the visible stimulus to research, development, and patenting generated by the zika and chikungunya epidemics in Brazil, such stimulus did not guarantee the arrival of new products on the market and population access to these products.
Con el fin de comprender cómo las epidemias de zika y chikunguña estimularon el desarrollo tecnológico, este estudio realizó la recopilación de datos epidemiológicos y la prospección tecnológica, utilizando datos del Instituto Nacional de la Propiedad Industrial (INPI) y Orbit Intelligence, y analizó los productos desarrollados y en desarrollo en todo el mundo y productos registrados en Brasil por la Agencia Nacional de Vigilancia Sanitaria (Anvisa). En 2016 se observó el mayor número de casos para ambas enfermedades. La prospección tecnológica nacional reveló que existe un interés mundial por desarrollar tecnologías para estas enfermedades y depositar sus patentes en Brasil, con las empresas como los principales depositantes. La prospección tecnológica mundial mostró que 2016 fue un hito importante en la evolución del número de patentes de zika y chikunguña, lo que sugiere que las epidemias brasileñas estimularon el desarrollo mundial de nuevos insumos para la salud. EE.UU. y China son las principales jurisdicciones, con las universidades como las mayores depositantes. El análisis global de productos reveló que solo 2 han llegado al mercado para zika y 1 para chikunguña, y las vacunas están en la categoría superior. La búsqueda en Anvisa reveló la existencia de más productos registrados para zika que para chikunguña. Los principales fabricantes legales son empresas brasileñas, con las solicitudes de registro realizadas principalmente por DiaSorin S.p.A., Eco Diagnóstica Ltda. y Chembio Diagnostics Brazil Ltda. Aunque hubo una notable promoción a la investigación, desarrollo y patentamiento generado por las epidemias de zika y chikunguña en Brasil, esto no implicó la llegada de nuevos productos al mercado y el acceso a ellos por parte de la población.
ABSTRACT
To study the material basis of cold and hot properties of traditional Chinese medicines (TCMs) in Lamiaceae and to establish a cold and hot properties identification model, a database of material components of TCMs in Lamiaceae was established. A three-level classification system of material components was used to obtain the material basis of cold and hot properties of the Lamiaceae family by using data mining methods such as frequency analysis, association rule analysis, logistic regression, and feature selection. Several identification models were established to recognize the cold and hot properties. The chi-square test results showed that the material composition ratios of cold and hot properties were significantly different at the first-level, second-level, and third-level classification (P < 0.05), and the differences varied as the levels of substance classification changed. The average coefficients of variation were 42.30%, 79.07%, and 91.51% at the first-level, second-level, and third-level classification levels, respectively. In other words, in terms of the percentage differences in material composition ratio, the first-level was smaller than the second-level, and the second-level was smaller than the third-level. The results of the association rule analysis showed that under the third-level classification, there were many effective association rules, and 27 core groups and 34 specific groups of chemical components were obtained based on these rules. 15 decisive groups were obtained from the feature selection results. Multinomial logistic regression analysis was used to successfully establish a cold and hot properties identification model with an overall accuracy of 89%. The material basis of cold and hot properties of TCMs in Lamiaceae is different and intersect with each other. Twenty-seven groups of chemical components, such as bicyclic diterpenes, are the core groups of cold and hot properties, of which 15 groups are the decisive groups. The cold and hot properties are often characterized by the interaction of multiple classes of substances, and a single class of substances often cannot be used to characterize the properties. The organic combination of multiple classes of substances is the material basis of cold and hot properties.
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Protein-protein interaction (PPI) plays an important role in the regulation of life. Most of the PPI interfaces are large and discontinuous, and it is difficult for small molecules to specifically bind to them. Peptides are critical in PPI surface interactions due to their higher affinity and specificity. However, peptides have some defects such as easy hydrolysis by protease and poor membrane permeability. Due to good biocompatibility and chemical diversity, cyclic peptides play an important role in drug discovery. Therefore, the development of efficient cyclic peptide construction methods has become a frontier issue in peptide drug research. In recent years, a series of new progresses have been made in the synthesis strategy and the application of cyclic peptides, providing powerful technical tools for the research and development of cyclic peptide drugs. In this review, the synthesis strategies of cyclic peptides and their application will be reviewed from four aspects: synthesis strategies, property improvement, biological activity and prospect.
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ObjectiveThe relevant laws among the growth habits， habitat， medicinal site and sex， taste and efficacy of rattan derived traditional Chinese medicine（TCM） were explored to strengthen the demonstration of the quality theory and to provide theoretical basis for the clinical use and resource development of rattan. MethodThe characteristics， effects， parts， families and growth habits of some TCM from rattan were analyzed. By referring to Chinese Flora， Chinese Materia Medica， Chinese Materia Medica Dictionary and other literature， a total of 48 kinds of Rattan from Chinese medicines included in the 2020 edition of Chinese Pharmacopoeia were screened out， and their property and meridian tropism， medicinal parts， habitat and classification of TCM were statistically analyzed. Excel 2013 and SPSS Statistics 26.0 were employed for statistical research. ResultThe results of the analysis of rattan derived Chinese medicine showed that in the families and genera， Tetrandaceae > Dioscorea > Leguminoa > Cucurbitaceae > Woodtonaceae， etc. In the nature， cold > warm > flat > cool > hot； Bitter > sweet > octane > acid. In the liver meridian， liver > lung > heart > spleen > stomach = bladder = kidney > large intestine. In medicinal parts， root and rhizome > vine stem > fruit seed > flower > vascular bundle = whole grass. In terms of habitat distribution， Guangdong > Guangxi > Yunnan > Fujian > Zhejiang， et al. In the classification of TCM， dispelling wind and dampness > clearing heat > improving water and dampness > promoting blood circulation and removing blood stasis. ConclusionRattan from TCM are mainly cold in nature， bitter in flavors， and entered liver meridian， and the root and stem of Rattan are mainly used in medicine， mostly distributed in the southeast coast of China. The main effects are to channel and activate collaterals， dispel wind and dehumidification， promote blood circulation and relieve pain， clear heat and detoxify. The morphology habit， growth environment and medicinal parts of Rattan from Chinese medicine were correlated with the property and efficacy. There was a certain correlation between the growth habits， habitat and medicinal site of rattan derived Chinese medicine and its sexual and taste effect， which provided reference for the development and utilization of rattan derived Chinese medicine resources.
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@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.
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D-mannose has many functional activities and is widely used in food, medicine, agriculture and other industries. D-mannitol oxidase that can efficiently convert D-mannitol into D-mannose has potential application in the enzymatic preparation of D-mannose. A D-mannitol oxidase (PsOX) was found from Paenibacillus sp. HGF5. The similarity between PsOX and the D-mannitol oxidase (AldO) from Streptomyces coelicolor was 50.94%. The molecular weight of PsOX was about 47.4 kDa. A recombinant expression plasmid pET-28a-PsOX was constructed and expressed in Escherichia coli BL21(DE3). The Km and kcat/Km values of PsOX for D-mannitol were 5.6 mmol/L and 0.68 L/(s·mmol). Further characterization of PsOX showed its optimal pH and temperature were 7.0 and 35 ℃, respectively, while its enzyme activity could be stably remained below 60 ℃. The molar conversion rate of 400 mmol/L D-mannitol by PsOX was 95.2%. The whole cells of PsOX and AldO were used to catalyze 73 g/L D-mannitol respectively. The reaction catalyzed by PsOX completed in 9 h and 70 g/L D-mannose was produced. PsOX showed a higher catalytic efficiency compared to that of AldO. PsOX may facilitate the enzymatic preparation of D-mannose as a novel D-mannose oxidase.