Cloning and gene functional analysis study of dynamin-related protein GeDRP1E gene in Gastrodia elata / 药学学报

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C3079H4973N883O933S19. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Construction of Evidence Body for Revision of Safety Information on Package Inserts of Chinese Patent Medicines in Post-marketing： Taking Xiaoke'an Capsules as an Example / 中国实验方剂学杂志

ObjectiveTo construct the evidence body for revision of safety information on package inserts of Chinese patent medicines in post-marketing by taking Xiaoke'an capsules as an example， so as to provide reference for the revision of instructions of Chinese patent medicines in post-marketing. MethodThe construction of the evidence body was guided by the theory of traditional Chinese medicine（TCM） and the Technical Guiding Principles for Revision of Safety Information Items in Instructions for TCMs After Marketing， and 8 categories and 25 specific items were taken as the main body of the evidence body， and information inclusion， integration， screening and improvement were carried out， then expert demonstrations were conducted， and finally modifications were made based on the opinions of the Center for Drug Evaluation to complete the revision of the safety information in the instructions of Xiaoke'an capsules. Result［Adverse reactions］ of Xiaoke'an capsules was revised to "monitoring data show that the following adverse reactions can be seen with this product：individual hypoglycemic reaction reports". ［Contraindications］ was revised to "contraindicated for those allergic to this product and its ingredients". ［Precautions］ was revised to "（1）pregnant women should use with caution， （2）elderly people should consult a physician， （3）people with spleen deficiency and dampness， spleen and stomach deficiency and cold， or those who eat less and have diarrhea should use with caution， （4）this product contains ginseng， should not be taken at the same time with TCM prescriptions or patent medicines containing veratrum and Wulingzhi， （5）pay attention to monitoring blood sugar during medication， （6）if any other discomfort occurs during medication， you should seek medical attention in time". The warning was revised to "use with caution by pregnant women， and pay attention to regular monitoring of blood sugar". ConclusionIn accordance with the content and process of the evidence body for the revision of safety information in the instructions， the revision of the safety information in the instructions of Xiaoke'an capsules has been completed， providing a strong basis for the rational and safe use of medication in the clinic.

Predictors for hemorrhagic transformation among patients with Ischemic stroke admitted in a Tertiary Hospital in the Philippines from July 2018-July 2019

Background@#Among the multiple scoring systems for hemorrhagic transformation, only few of these address spontaneous hemorrhagic transformation after an ischemic stroke, with most done with Western population data. @*Objectives@#This study aims to identify the predictors for hemorrhagic transformation among patients with ischemic stroke admitted in a tertiary hospital in Cebu City, Philippines.@*Methods@#This is a retrospective cohort study of patients with ischemic stroke admitted in a tertiary hospital in Cebu City. Patients’ baseline characteristics, clinical, and radiologic data were collected. Chi square test and t-test were used to determine which variables were significantly different between patients with and without hemorrhagic transformation. Odds ratio (OR) and 95% confidence interval (CI) were determined to measure the association between the different variables and hemorrhagic transformation. @*Results@#A total of 500 ischemic stroke patients were included in the study. There were 28 (6%) ischemic stroke patients with Hemorrhagic Transformation. The mean age of these patients is 66.93 ± 12.42 years, 48.8% male, 10.8% had atrial fibrillation, and 2.4% had myocardial infarction. Controlling for the effect of confounders, white blood cell count (OR 1.11; 95% CI 1.03-1.19), myocardial infarction (OR 5.25; 95% CI 1.13-24.34), and presence of brain edema (OR 2.86; 95% CI 1.05-7.80) were significant predictors of hemorrhagic transformation.@*Conclusion@#White blood cell count, presence of brain edema, and myocardial infarction were significantly associated with hemorrhagic transformation among ischemic stroke patients.

Characteristics of STAT Family Association with Breast Cancer and Intervention Effect of Traditional Chinese Medicine / 中国实验方剂学杂志

As the pace of society increases and lifestyles change， the incidence and mortality rates of breast cancer continue to rise. Targeted therapies are now promising in the treatment of breast cancer， and a variety of protein targets have been identified to play an important role in the development of breast cancer. Among them， signal transducer and activator of transcription （STAT） proteins constitute a crucial group that serves as important targets for transducing cellular transcriptional information， which can regulate downstream cell proliferation， apoptosis， cell migration， invasion， angiogenic factors， etc. and then affect the progression of breast cancer. The STAT family is closely associated with the inflammatory response to tumors and plays a landmark role in tumor development as well as in diagnosis and prognosis. The "inflammation-cancer" transformation refers to the process in which the inflammatory microenvironment caused by uncontrolled inflammation promotes normal cells to become cancerous. According to the theory of Chinese medicine， "heat toxicity" in "cancer toxicity" corresponds to inflammation， which is closely related to tumor development. As a major link associated with the inflammatory response， the STAT family has a promising role in the development and treatment of a variety of tumors， but its relevance to breast cancer remains inadequately explored. Chinese medicine has been shown to have good efficacy in the prevention and treatment of breast cancer， and some current studies have shown that the active ingredients and compounds of Chinese medicine have certain intervention effects on breast cancer-related STAT proteins， but there has not been a systematic review. In order to better sort out and summarize the studies on the effects of Chinese herbal medicines based on the STAT family interventions in breast cancer， this paper reviewed the studies on Chinese herbal medicines acting on the STAT family in recent years， aiming to provide new ideas for clinical applications in breast cancer and to provide thoughts for the development of STAT protein-based drugs.

The Prevention and Treatment of Pulmonary Nodules “Nodule-cancer Transformation” Based on the View of “Disease with Latent Pathogen Induced by a New Pathogen” / 中医杂志

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

O desamparo em Freud e a política como ruptura dos possíveis / Helplessness in Freud and politics as a rupture of the possible / Le délaissé chez Freud et la politique comme rupture du possible / Lo desamparo en Freud y la política como ruptura de lo posible

Este trabalho visa delinear o conceito de desamparo por meio da metapsicologia freudiana e como isso implica outra forma de pensar a política. Desse modo, o desamparo não é concebido unicamente como a vulnerabilidade do bebê ao nascer, mas, também, como a falta de respostas às excitações internas. Tal estado de desamparo é radicalizado a partir da concepção de pulsão de morte construída por Freud. A pulsão de morte gera processos de desabamentos, rupturas, desligamentos e despossessão, essenciais para a própria vida se complexificar. Nesse sentido, propomos o desamparo como afeto político central quando pensamos em transformação. A partir do desabamento de si e da abertura radical ao contato do outro, podemos experimentar outras formas de experiências, outras formas de afetação e, consequentemente, a construção de corpos políticos rumo à transformação política radical

This paper outlines the concept of helplessness through Freudian metapsychology and by doing so imply a new way of thinking about politics. Helplessness is not conceived simply as the newborn's vulnerability, but also as the lack of response to internal excitements. Such an estate is radicalized by Freud's concept of death drive, which generates processes of collapsing, ruptures, unplugging and dispossession that are essential for turning life complex. In this sense, we propose helplessness as a main political affection when referring to transformation. By the collapse of oneself and the radical opening to contact with others, one may experience other ways of experiencing and of being affected and, consequently, the construction of political bodies leading to the radical transformation of politics

Cet article présente le concept de délaissé à travers la métapsychologie freudienne et, ce faisant, lui imprime une nouvelle façon de penser la politique. Le délaissé n'est pas simplement conçu comme la vulnérabilité du nouveau-né, mais aussi comme une absence de réponse aux excitations internes. Tel état est radicalisé par le concept de pulsion de mort de Freud, qui produit des processus de glissement, de rupture, d'arrêt et de dépossession essentielles à la complexification de la vie. En ce sens, nous proposons le délaissé comme principale affection politique lorsqu'il est question de transformation. Par le glissement de soi-même et l'ouverture radicale au contact avec les autres, nous pouvons expérimenter d'autres façons de vivre et d'être affecté et, par conséquent, la construction de corps politiques vers à la transformation politique radicale

Este artículo pretende esbozar el concepto de desamparo a través de la metapsicología freudiana y cómo esto implica otra forma de pensar sobre política. De esa manera, la impotencia no solo se concibe como la vulnerabilidad del bebé al nacer, sino también debido a la falta de respuestas a las excitaciones internas. Tal estado de desamparo se radicaliza desde la concepción del impulso de muerte construido por Freud. El impulso de la muerte genera procesos de colapsos, rupturas, desconexiones y desposesión esenciales para que la vida misma se vuelva más compleja. En este sentido, proponemos lo desamparo como un afecto político central cuando pensemos en la transformación. Desde el colapso de uno mismo y la apertura radical al contacto con el otro, podemos experimentar otras formas de experiencias y otras formas de afectación y,en consecuencia, la construcción de cuerpos políticos hacia una transformación política radical

Indications of changes in hunting culture in the Central-South Region of Brazil in the last 25 years: a systematic literature review / Indícios de mudanças na cultura da caça na região Centro-Sul do Brasil nos últimos 25 anos: uma revisão sistemática da literatura

Abstract Hunting has been banned in Brazil by a Federal Law (No. 5197), except in a few cases where it has been regulated, for over 50 years now. Since then, the country suffered dramatic land use change, especially in its Central-South region. In this study we investigate the possible influence of land use change on hunters' socioeconomic profile (e.g., education, income) and motivation (e.g., leisure or subsistence) in the Central-South Brazil since the implementation of the ban policy. On a systematic literature review we found 18 papers about hunting activities and hunters' profile in this region, one third of which presented evidence of change in hunting activities or in hunters' profile somehow related to land use change since 1967. With this small number of articles, it was not possible to fully assess whether there was a change in hunting culture in the target region as a result of changes in land use. However, the found studies present consistent evidence of changes in hunting culture, especially in regard to a trade on the hunted species, hunting techniques and hunters' profile. Considering the relevance of hunting in agricultural landscapes for wildlife conservation, we hope the present results stimulate further studies on this field.

Resumo A caça é uma atividade proibida no Brasil por uma Lei Federal (nº 5.197), exceto em alguns casos onde é regulamentada, há mais de 50 anos. Desde então, o país sofreu uma mudança dramática no uso da terra, especialmente na região Centro-Sul. Neste estudo investigamos a possível influência da mudança no uso da terra no perfil socioeconômico (e.g., educação, renda) e motivação (e.g., lazer, subsistência) dos caçadores no Centro-Sul do Brasil desde a implementação da política de proibição. Em uma revisão sistemática da literatura encontramos 18 artigos sobre atividades cinegéticas e o perfil dos caçadores nesta região, sendo que um terço apresentou evidências de alguma mudança nas atividades cinegéticas ou no perfil dos caçadores, relacionada à mudança do uso da terra desde 1967. Com este pequeno número de artigos, não foi possível avaliar plenamente se houve mudança na cultura cinegética na região-alvo em decorrência de mudanças no uso da terra. No entanto, os estudos encontrados apresentam evidências consistentes de mudanças na cultura da caça, principalmente no que diz respeito ao comércio das espécies caçadas, técnicas de caça e perfil dos caçadores. Considerando a relevância da caça em paisagens agrícolas para a conservação da vida selvagem, esperamos que os presentes resultados estimulem novos estudos nesta área.

miR-186 regulates epithelial-mesenchymal transformation to promote nasopharyngeal carcinoma metastasis by targeting ZEB1

Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. Methods The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

Líquen Plano Oral e seu Potencial de Malignização / Lichen Planus and its potencial for malignancy

Objetivos: Instruir e orientar ao cirurgião dentista e demais profissionais de saúde a importância da detecção e rastreio precoce de lesões pré-malignas. Revisão de Literatura: O Líquen Plano Oral é uma condição dermatológica crônica, de origem auto-imune, relativamente comum na população, que atinge o epitélio de mucosa e pele, sendo considerada, pela Organização Mundial de Saúde (OMS), uma desordem potencialmente maligna quando associado a áreas de ulceração. A revisão de literatura foi realizada nas bases de dados PubMed e Lilacs. Buscamos investigar o potencial de malignização do Líquen Plano Oral associado a condições erosivas, analisando o processo de carcinogênese no processo inflamatório. Conclusão: Conclui-se que o objeto de estudo ainda é um assunto pouco explorado pela literatura, porém há indícios etiopatológicos que enfatizam o processo de malignização oriundo de uma lesão pré-maligna como o Líquen Plano Oral. Além disso, enfatizamos a importância do diagnóstico precoce das lesões estomatognáticas, para que assim possamos aumentar as chances de cura do paciente.(AU)

Objectives: To instruct and guide dentists and other health professionals on the importance of early detection and screening of pre-malignant lesions. Literature Review: Oral Lichen Planus is a chronic dermatological condition, of autoimmune origin, relatively common in the population, which affects the epithelium of the mucosa and skin, being considered, by the World Health Organization (WHO), a potentially fatal disorder. malignant when associated with areas of ulceration. A literature review was performed on the PubMed and Lilacs databases. We sought to investigate the potential for malignancy of Oral Lichen Planus associated with erosive conditions, analyzing the process of carcinogenesis in the inflammatory process. Conclusion: It is concluded that the object of study is still a subject little explored in the literature, but there are etiopathological accusations that emphasize the process of malignancy arising from a pre-malignant lesion such as Oral Lichen Planus. In addition, we emphasize the importance of early diagnosis of stomatognathic lesions, so that we can increase the patient's chances of cure.(AU)

URBANIZATION IN KARNATAKA; A GEOGRAPHICAL APPROACH

Urbanization is a world-wide process and it is a cause and effect of heightened economic progress in a region. It plays an enormous role in social transformation and economic mobility all over the world. In fact, the process and level of urbanization has been transforming the developing countries from 'countries of villages' to 'countries of towns and cities'. With 31.16 percent urbanites lived in 2011, India is at a low level of urbanization compared with the developed nations. There exists large inter-regional disparities in different parts of the nation as far as level of urbanization is concerned. The present paper is an attempt to study the trends, degrees and tempo of urbanization and urban morphology in Karnataka from 1901 to 2011. It is the 7th largest state in India with 38.67 percent of urbanites living in 347 towns and cities as of 2011, which is 7.51 points above the national average in terms of urbanization and plays a signicant role in the state's as well as country's economy and progress of IT and BT sector. The paper is an effort to analyses the regional disparity in the process and level of urbanization among the districts of the state from 1991 to 2011. Finally, the study also enlightens the socio-economic consequences of this inter-regional disparity in urbanization in Karnataka. Present study is mainly based on the secondary sources of data and is collected from Indian Census Handbooks of Karnataka and other related reports. After collecting data, these were analysed in a suitable manner by using appropriate statistical and cartographic techniques. Results show that the state exhibits a uctuating trend in level of urbanization with a high regional variation and a high disparity in the concentration of urbanities. Disparities exist at the levels of urbanization in state shown that, Bangalore is the most urbanized district with 90.94 percent followed by Dharwad (56.82 percent) district and on the other end of this scale Kodagu with 14.61 percent, was the least urbanized district in the state. 78.24 percent of urbanities lived in only 19 percent of urban centres and the remaining 81 percent of towns contained only 21.76 percent of the state's urbanities. Thus, urbanization in Karnataka is a by-product of the demographic explosion, poverty encouraged rural-urban migration and reclassication of towns and it also reects uneven economic progresses across the state and needs special attention.

Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy

Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.

Repercussion Of Cultural Clashes In Manju Kapur's The Immigrant

Manju Kapur primarily writes about the plight and repression of Indian women as well as their resistance to it. Marriage, families, complexities in relationships and separation are some of the most pervasive themes in her fiction. Manju Kapur's The Immigrant is a story of dislocation and cultural conflict. The novel revolves around a thirty-one-year-old spinster, Nina, who lived with her widowed mother in Delhi. She marries Ananda, an NRI, dentist and she flies to Canada to start her new life. The paper discusses how the novelist brings up the life of a married woman, with only her husband to talk to, all alone in a foreign land where Indian culture and individualism have often remained alien ideas. This paper delves into the issues of alienation and the search for cultural identity, as well as transformation of Nina and Ananda as a result of becoming an immigrant.

Sclerosing angiomatoid nodular transformation of spleen with calcifying fibrous pseudotumor: A rare case with unusual association

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare benign vascular lesion of the spleen that was first described in 2004. SANT is associated with other concurrent diseases, mostly malignancies. Calcifying fibrous pseudotumor (CFPT) is a tumor-like lesion usually arising from soft tissue or peritoneal sub-serosa. Both SANT and CFPT are considered to be variants of the inflammatory myofibroblastic tumor. We report the rare case of a 24-year-old female presenting with a left abdominal mass that was clinically diagnosed as an extraintestinal gastrointestinal stromal tumor (GIST). Histopathological examination revealed SANT of spleen and CFPT. We report this case due to its rarity of occurrence and unusual association of SANT with CFPT.

T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Decolonialidade e Serviço Social: um debate emergente / Decoloniality and Social Work: an emerging debate

Resumo: Este artigo reflete acerca das contribuições do pensamento decolonial para o Serviço Social. Considera a colonialidade e a decolonialidade como ferramentas de análise e projeto ético e político, que oferecem alternativas de conhecimento e transformação social devido à diversidade epistêmica teórica, política e pedagógica. Propõe complexificar e questionar a lógica de produção de conhecimento moderna/ocidental, evidenciando categorias e conceitos úteis à prática e à produção científica da profissão.

Abstract: This article reflects on the contributions of decolonial thinking to social work. It considers coloniality and decoloniality as analysis tools and ethical and political projects that offer alternatives for knowledge and social transformation due to theoretical, political and pedagogical epistemic diversity. It proposes to make more complex and question the logic of modern/Western knowledge production, highlighting categories and concepts that are useful to the practice and scientific production of the profession.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

LncRNA UNC5B-AS1 promotes proliferation and epithelial-mesenchymal transition of cervical cancer cells by regulating Toll-like receptor signaling pathway / 中国药理学通报

Aim To investigate the effects of long non-coding RNA(lncRNA)UNC5B-AS1 on the proliferation and epithelial mesenchymal transformation(EMT)of cervical cancer. Methods GEO and TCGA databases were used to download data sets and differential expression analysis was performed. qRT-PCR was used to verify the differential expression of lncRNA UNC5B-AS1 in normal and cancerous cervical tissues.The interference and overexpression of lncRNA UNC5B-AS1 were transfected into cervical cancer cell lines, and plate cloning, CCK-8 and EdU experiments were used to detect the effect of lncRNA UNC5B-AS1 on the pro-liferation of cervical cancer cells.Transwell assay was used to detect its effect on migration and invasion of cervical cancer cells.The expression levels of EMT-related genes E-Cadherin, N-Cadherin and Vimentin were detected by Western blot. Transcriptome sequencing was used to obtain the signal pathway regulated by lncRNA UNC5B-AS1, and to verify the expression level of related genes. Results RNA microarray and bioinformatics analysis showed that the expression level of lncRNA UNC5B-AS1 in cervical cancer was significantly higher than that in normal cervical tissue, and correlated with the overall survival time of patients.Compared with the negative control group, knockdown lncRNA UNC5B-AS1 could reduce the proliferation, migration and invasion of cervical cancer cells, while overexpression could promote the proliferation, migration and invasion of cervical cancer cells. Western blot showed that lncRNA UNC5B-AS1 could regulate EMT of cervical cancer cells. Transcriptome sequencing showed that lncRNA UNC5B-AS1 could regulate Toll like receptor(TLR)signaling pathway. qRT-PCR and Western blot results showed that the expression levels of TLR-related genes IL-6 and TICAM2 in the knockdown and overexpression lncRNA UNC5B-AS1 group were significantly changed(P<0.05). Conclusions LncRNA UNC5B-AS1 is highly expressed in cervical cancer. Overexpression of lncRNA UNC5B-AS1 may enhance TLR signaling pathway activity, thereby promoting proliferation and EMT of cervical cancer cells.

Form Properties of Moving Targets Bias Smooth Pursuit Target Selection in Monkeys / 神经科学通报·英文版

During natural viewing, we often recognize multiple objects, detect their motion, and select one object as the target to track. It remains to be determined how such behavior is guided by the integration of visual form and motion perception. To address this, we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task. We found that pursuit responses were biased toward the motion direction of a target with a hole. By computing the relative weighting, we found that the target with a hole exhibited a larger weight for vector computation. The global hole feature dominated other form properties. This dominance failed to account for changes in pursuit responses to a target with different forms moving singly. These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.

FOXO1-miR-506 axis promotes chemosensitivity to temozolomide and suppresses invasiveness in glioblastoma through a feedback loop of FOXO1/miR-506/ETS1/FOXO1 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.

Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.