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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández Fernado García-Dolores Humberto Nicolini andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(INCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

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Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic

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World Journal of Diabetes 2024年第6期15卷 1374-1380页

作者： Angelo Emilio Claro Clelia Palanza Marianna Mazza Alessandro Rizzi andrea Corsello Linda Tartaglione Giuseppe Marano Giovanna Elsa Ute Muti Schuenemann Marta Rigoni Alfredo Pontecorvi Luigi Janiri Paola Muti Dario Pitocco Diabetes Care Unit Department of Medical and Surgical SciencesFondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of Biomedical Surgical and Dental SciencesUniversity of MilanMilan 20122Italy Istituto Italiano di Antropologia ISItARome 00100Italy Unit of Psychiatry Department of NeurosciencesFondazione Policlinico Universitario A Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Dipartimento di Medicina e Chirurgia Traslazionale UniversitàCattolica del Sacro CuoreRome 00168Italy Health Research Methods Evidence and Impact DepartmentMcMaster UniversityOntario 1280Canada Department of Endocrine-Metabolic and Dermo-Rheumatology Fondazione Policlinico Universitario A Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy

Common psychiatric disorders(CPDs)and depression contribute significantly to the global epidemic of type 2 diabetes(T2D).We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs,promotes the establishment of emotional eating,activation of the reward system,onset of overweight and obesity and,ultimately the increased risk of developing *** plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexonebupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction,but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug *** hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.

关键词： Depression Glucagon-like peptide-1 receptor agonists Diabetes mellitus type 2 Stress psychological Sleep wake disorders Food addiction

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Outcomes of a non-randomised audit of single pigtail suture stents in urolithiasis management of Asian patients in Singapore

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Asian Journal of Urology 2024年第2期11卷 324-330页

作者： Ee Jean Lim Zhen Wei Choo Reshma Mangat Pradeep Durai Sarvajit Biligere Yiquan Tan Loh Hin Yeung Marcus Nicole andrea Seet Li Ting Chin Tiong Heng Stefania Ferreti Vineet Gauhar Urology Department Singapore General HospitalSingapore Urology Department Tan Tock Seng HospitalSingapore Urology Department Ng Teng Fong HospitalSingapore Urology Department Azienda Ospedaliera-Uiversitaria(Hospital and University of Parma)ParmaItaly

Objective:Double-J(DJ)ureteric stents are commonly placed perioperatively for semirigid or flexible ureteroscopic renal *** is believed that lesser stent material within the bladder mitigates stent-related *** study aimed to evaluate the J-Fil ureteral stent,a single pigtail suture stent compared with conventional DJ stent in relation to stent symptoms in an Asian population undergoing ureterorenal ***:Based on internal audit committee recommendation approval,the records of 50 patients retrieved,available data of 41 patients who were prospectively enrolled into two groups(Group 1[J-Fil stent group],n=21 and Group 2[DJ stent group],n=20)between August 2020 to January 2021,were *** compared were nature of procedure,stone location and size,ease of deployment or removal,and complications.A modified universal stent symptom questionnaire was used to assess morbidity of stent symptoms within 48 h of insertion and at ***:Both groups had similar median age,distribution in male to female ratio,and stone *** overall median universal stent symptom questionnaire score at insertion was similar for bladder pain,flank or loin pain,and quality of life between Group 1 and 2;however,at removal Group 1 fared significantly better than Group 2,especially for flank or loin pain and pain at *** groups had similar ease in insertion with no hospital ***:Our audit favoured the single pigtail suture stent in Asian ureters in mitigating stent-related *** showed a good safety profile with easy deployment and *** promises a new standard in stenting.

关键词： Stent Ureteroscopy Pigtail suture stent Asianpatient Flexible ureteroscopic renal surgery

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Efficacy of 1% Permethrin and 2% Permethrin Combined with 1% Piperonyl Butoxide against Rhipicephalus sanguineus Ticks in Naturally Infested Dogs

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Pharmacology & Pharmacy 2024年第7期15卷 237-247页

作者： andrea Márquez-Aguado Froylán Ibarra-Velarde Joaquín Ambia-Medina Rosa Arias-García Departamento de Parasitologa Facultad de Medicina Veterinaria y Zootecnia Universidad Nacional Autnoma de Mxico Mexico City Mxico Laboratorios Salud Animal S.A de C.V. Mexico City Mxico

The aim of the present study was to compare the ixodicide efficacy of 1% permethrin applied as a shampoo-bath in single treatment and a combined formulation of 2% permethrin + 1% piperonyl butoxide applied as powder in a single treatment against Rhipicephalus sanguineus ticks, in naturally infested dogs. Eighteen adult cross-mixed dogs, harboring to at least 20 ticks/animal, were selected on pre-treatment live tick counts. On day 0, the dogs were then divided in 3 groups of 6 animals each, for treatment: Group 1 (G1) received 1% permethrin applied as shampoo-bath (approximately 10 ml/kg bw), according to label instructions. G2 was treated with 2% permethrin + 1% piperonyl butoxide applied as powder, and rubbed as massage on the body, as recommended by the producer. G3 served as a non-treated control. After the treatment, the dogs were checked out for live ticks counting on days 0, 1, 7, and 14. The ixodicide efficacy was assessed based on the percentage reductions of ticks on the days analyzed post-treatment, with respect to the untreated control. Results showed that permethrin alone removed ticks on 81%, 93.1% and 89.6% for days 1, 7 and 14, respectively. The combined formulation of 2% permethrin + 1% piperonyl butoxide exerted a better efficacy of 98.8, 97.7 and 97.0%, respectively. It is concluded that this combined formulation was highly effective at rapidly repelling and killing Riphicephalus sanguineus ticks on naturally infected dogs, showing a significant effect on days 1, 7 and 14 after tick exposure. The sustained high and quick level of efficacy of this combination may well interfere with the transmission of Riphicephalus sanguineus ticks. It is concluded that the sustained high level of efficacy of the permethrin + piperonyl butoxide combination may well exert an additive effect and could interfere with the transmission of Riphicephalus sanguineus ticks.

关键词： Efficacy Permethrin Permethrin + Piperonyl Butoxide Riphicephalus sanguineus Dogs

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Sensorial Evaluation and Physical Chemical Characterization of a Beverage Based on Whey and β-Glucans as a Potential Prevention of Nonalcoholic Steatohepatitis

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Food and Nutrition Sciences 2024年第8期15卷 770-789页

作者： Adriana Hernandez Santana andrea Jimena Valdés Alvarado Sandra Karina Espinoza Stephany Bernardeth Lanza Aguilar Food Science Department Zamorano Pan-American Agricultural School Tegucigalpa Honduras

Whey and B-glucans are functional food ingredients that contribute to the prevention of non-communicable diseases. The objective of the study was to develop a functional beverage based on whey, B-glucans, and blackberry concentrate for the prevention of nonalcoholic steatohepatitis, determining its sensory, physicochemical, and nutritional qualities. The following phases were developed: 1) formulation with 75%, 85%, and 90% whey and 25%, 15%, and 10% blackberry concentrate, with a fixed amount of 0.243 g β-glucans in 100 ml;2) microbiological analysis to ensure the safety of the beverage;3) sensory analysis with untrained panelists to assess the degree of preference (appearance, color, odor, flavor, viscosity, acidity, sweetness), and general acceptance, with a seven-point hedonic scale to rate the level of acceptability;4) physicochemical and nutritional characterization of the beverage with the highest acceptance. An experimental design using complete random blocks was employed. Data analysis was performed with variance (ANDEVA) and mean DUNCAN separation at a 95% confidence level, using SAS®. A correlation study was conducted on acceptance analysis. A nutritional label was developed for the control beverage and the treatment with the highest acceptance. The formulation with 75% whey, 25% blackberry concentrate, and 0.243 g of β-glucan obtained the highest acceptance, with flavor and sweetness being the attributes that contributed to its acceptance. Nutritionally, the beverage with 80 cal, would be considered fortified with fiber (2 g), free of cholesterol, sodium, and saturated fat, according to the Central American Technical Regulation on Nutritional Labeling (Version 67.01.60:10). It is recommended that the effect of this beverage be measured to determine the benefits.

关键词： Fatty Acids Fatty Liver Glucans Whey

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Antioxidant treatment for oligoasthenoteratozoospermia and varicocele:a DBPC trial to evaluate the impact of age and body mass index

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Asian Journal of Andrology 2024年第3期26卷 239-244页

作者： Gian Maria Busetto Bernarde F Rodrigues Ashraf Virmani andrea Checchia Antonella Ninivaggi Anna Ricapito Giovanni Barbieri Piero Fischetti Ugo G Falagario Pasquale Annese Nicola d’Altilia Vito Mancini Matteo Ferro Felice Crocetto Angelo Porreca Carlo Bettocchi Luigi Cormio Ashok Agarwal Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Department of Urology Human Reproduction SectionFederal University of Sao PauloSao Paulo 05403-000Brazil Alfasigma Healthscience Utrecht 3528 BGThe Netherlands Urology Unit “G.Tatarella”HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IEO)IRCCSMilan 20142Italy University of Naples Federico II Naples80126Italy Department of Oncological Urology Veneto Institute of Oncology(IOV)IRCCSPadua 35039Italy Urology Unit “L.Bonomo”HospitalAndria 70031Italy Global Andrology Forum Moreland HillsOH 44022USA

Oxidative stress is one of the main mechanisms responsible for male *** conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the *** are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe *** reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive *** double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on *** concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this *** conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

关键词： aging antioxidants body mass index oligoasthenoteratozoospermia varicocele

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学习的艺术——艾儿思国际幼儿园

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中国建筑装饰装修 2024年第12期 34-41页

作者： Filippo Gabbiani andrea Destefanis Kokaistudios

要创造一所成功的艺术性幼儿园，一个可以让儿童学习并与创意媒介互动的场所，那么幼儿园本身必须也是一件艺术品。这即是Kokaistudios将武汉曾经的一处营销中心改造成艾儿思国际幼儿园的动力所在，并让它成为构建在创意、社区和凝聚力...

要创造一所成功的艺术性幼儿园，一个可以让儿童学习并与创意媒介互动的场所，那么幼儿园本身必须也是一件艺术品。这即是Kokaistudios将武汉曾经的一处营销中心改造成艾儿思国际幼儿园的动力所在，并让它成为构建在创意、社区和凝聚力价值观上的早教机构。Kokaistudios的设计以儿童为导向，为用户创造了自然的好奇心和互动之旅。设计为避免线性动线和过于单一的层次，安置了多种体量和有趣的探索点位；原本单一的走廊被流动的内部社交空间和相互连接的室内操场所取代；圆形元素的标识则体现出公共区域的连续性。

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生活与自然间的平衡——抽象北欧森林中的厨电展厅

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中国建筑装饰装修 2024年第6期 30-35页

作者： Shirley Dong andrea Maira 八荒设计

八荒设计近日完成了北欧厨电品牌ASKO在国内的首家旗舰体验中心设计，八荒设计负责体验中心的建筑立面改造以及室内设计。体验中心位于浦东老船厂边的陆家嘴滨江金融城，沿街建筑各自有着分别代表自己企业形象的不同建筑立面风格。如何...

八荒设计近日完成了北欧厨电品牌ASKO在国内的首家旗舰体验中心设计，八荒设计负责体验中心的建筑立面改造以及室内设计。体验中心位于浦东老船厂边的陆家嘴滨江金融城，沿街建筑各自有着分别代表自己企业形象的不同建筑立面风格。如何将品牌价值表达于空间？八荒设计将“责任”定为设计主题，一方面表达品牌对环境的关注，

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光线雕琢，焕新内向旧区——北京保利广场

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中国建筑装饰装修 2024年第6期 22-29页

作者： Filippo Gabbiani andrea Destefanis Kokaistudios

近期，Kokaistudios改造了一对封闭、陈旧的商业建筑，使其与新时代产生共鸣，并为北京环路上一处极具挑战性的多功能地块注入了生机和活力。随着北京城市规模的不断扩大，有些在几十年前建造的建筑已逐渐不能够适应新的城市语境。位于...

近期，Kokaistudios改造了一对封闭、陈旧的商业建筑，使其与新时代产生共鸣，并为北京环路上一处极具挑战性的多功能地块注入了生机和活力。随着北京城市规模的不断扩大，有些在几十年前建造的建筑已逐渐不能够适应新的城市语境。位于北五环上的两座商业建筑就是这种情况，它们像是一个个内向封闭的巨大盒子，内部几乎没有自然光，而且与周围新城市化的环境相隔。

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