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The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,fAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin f2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

121份澳大利亚小麦材料抗条锈病鉴定及分子检测

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植物病理学报 2024年

作者：黄洁杨金叶 Davinder Singh Peng Zhang robert f.Park 王保通李强西北农林科技大学植物保护学院作物抗逆与高效生产全国重点实验室 Plant Breeding Institute The University of Sydney

条锈病是世界范围内小麦上的重要病害，培育和种植抗病品种是防治条锈病最经济有效的措施。为明确澳大利亚小麦材料的抗条锈病水平及所含抗条锈病基因，本研究利用8个澳大利亚小麦条锈菌流行小种对121份小麦材料进行了苗期抗性鉴定，同... 详细信息

条锈病是世界范围内小麦上的重要病害，培育和种植抗病品种是防治条锈病最经济有效的措施。为明确澳大利亚小麦材料的抗条锈病水平及所含抗条锈病基因，本研究利用8个澳大利亚小麦条锈菌流行小种对121份小麦材料进行了苗期抗性鉴定，同时应用小麦抗条锈病基因Yr5、Yr9 (1B/1R)、Yr10、Yr15、Yr17及Yr26的特异性分子标记进行了分子检测。结果表明，121份小麦材料中，21份(17.35%)对所有供试条锈菌小种均表现抗病，7份(5.79%)均表现感病，其他材料对一个或多个条锈菌小种表现抗病。分子检测结合抗病性鉴定结果显示，3份(2.48%)可能含有Yr5基因，15份(12.40%)可能含有Yr9,9份(7.44%%)可能含有Yr10,6份(4.96%)可能含有Yr17,19份(15.70%)可能含有Yr26，没有检测到Yr15基因。此外，其中13份材料同时检测到两个或两个以上的抗条锈病基因，还有19份材料可能含有其他已知或未知的抗条锈基因。本研究为121份澳大利亚小麦材料的合理利用和小麦抗病育种提供了科学依据。

关键词：小麦条锈病抗性鉴定抗病基因分子检测

Integrins and their potential roles in mammalian pregnancy

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Journal of Animal Science and Biotechnology 2024年第1期15卷 1-19页

作者： Gregory A.Johnson robert C.Burghardt fuller W.Bazer Heewon Seo Joe W.Cain Department of Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843‑4459USA Department of Animal Science College of Agriculture and Life SciencesTexas A&M UniversityCollege StationTX 77843‑2471USA

Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in fig. 1, 2, 3, 4, 5 and 6 are present throughout the sc

关键词： Humans Implantation Integrins Pigs Pregnancy Rodents Sheep

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

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World Journal of Orthopedics 2024年第8期15卷 754-763页

作者： Mahad M Hassan Aliya G feroe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns Charles f Mitchell robert L Parisien Daniel A Maranho Eduardo N Novais Young-Jo Kim Ata M Kiapour Department of Orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of Orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of Orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of Orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of Orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of Orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of Biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular *** To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric *** hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip *** femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head *** In both sexes,the residual volume increased by age(Pficantly smaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity *** were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip femoral head Sphericity Skeletal growth Sex differences

ITPK1 is an InsP_(6)/ADP phosphotransferase that controls phosphate signaling in Arabidopsis

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Molecular Plant 2024年第7期17卷 1151-1157页

作者： Esther Riemer Danye Qiu Debabrata Laha robert K.Harmel Philipp Gaugler Verena Gaugler Michael frei Mohammad-Reza Hajirezaei Nargis Parvin Laha Lukas Krusenbaum Robin Schneider Adolfo Saiardi Dorothea fiedler Henning J.Jessen Gabriel Schaaf Ricardo f.H.Giehi 不详

(Molecular Plant 14,1864-1880;November 12021)We identified a mistake made when calculating the absolute concentrations of inositol(pyro)phosphates derived from CE-ESl-MS measurements reported in the originally published version of our *** to a calculation error when determining concentrations per fresh biomass,the absolute values shown in the manuscript are approximately 30-fold lower than they should *** mistake affects figures 2D,3C,4C,and 7D and figures S4,S11B,S13,and *** all conclusions made in the article referred to relative differences between genotypes and treatments,they remained unaffected by these mistakes.

关键词： ipt Arabidopsis absolute

Characterization of squash polysaccharide and the anti-diabetic effect on type 2 diabetic rat revealed by urine metabolomics analysis

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food Science and Human Wellness 2024年第5期13卷 2937-2946页

作者： Li Liang fuming Zhang Quanhong Li Baoguo Sun Yuyu Zhang robert J.Linhardt Beijing Advanced Innovation Center for food Nutrition and Human Health Beijing Key Laboratory of Flavor ChemistryBeijing Technology and Business University(BTBU)Beijing 100048China Departments of Chemical and Biological Engineering Chemistry and Chemical BiologyBiomedical Engineering and Biological ScienceCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroy 12180USA College of food Science and Nutritional Engineering China Agricultural UniversityBeijing 100083China China National Engineering Research Center for fruit and Vegetable Processing Beijing 100083China

The present study reports the structural characteristics of 3 polysaccharide fractions(SPS-f1,SPS-f2 and SPS-f3)isolated and purified from ***-f1(molecular weight(Mw)=12.30 kDa)and SPS-f2(Mw=19.40 kDa)were likely to contain HG and RG-I domain of pectic polysaccharide,***-f2(Mw=270.4 kDa)was mainly composed of rhamnose,galactose and *** treatment with SPS decreased body weight gain,glucose and TG levels in type 2 diabetes ***,25 differential metabolites were identified based on urinary metabolomics analysis,which are crucial to the anti-diabetic effect of *** regulation of nicotinamide N-oxide,histamine,cis-aconitate,citrate,L-malic acid,3-(3-hydroxyphenyl)propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism,gut microbiota and *** of surface plasmon resonance revealed the binding kinetics with galectin-3(Gal-3)and fibroblast growth factor 2(fGf2).The K_(D)values of SPS-f2 and SPS-f3 to Gal-3 were 4.97×10^(-3)and 1.48×10^(-3)mol/L,indicating a weak binding *** 3 fractions showed moderate binding to fGf2 and the affinity was SPS-f3>SPS-f2>***,the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.

关键词： Polysaccharide Metabolomics Type 2 diabetes Surface plasmon resonance

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Prevalence of Precancerous Lesions Based on Digital Cervicography with VIA/VILI among Women Positive for High-Risk Human Papillomavirus Serotypes: A Screening Center-Based Study in Cameroon

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Open Journal of Obstetrics and Gynecology 2024年第6期14卷 967-978页

作者： Jeffrey-Lewis Nzang Cliford Ebontane Ebong Simon Manga florence Manjuh félix Essiben Isidore Tompeen Judith Seungue Serge robert Nyada Jeanne Hortence fouedjio Ymele fouelifack Julius Sama Dohbit Kloukanmey Zonal Hospital Mdecins Sans Frontires Kloukanmey Benin faculty of Medicine and Biomedical Sciences University of Yaound 1 Yaound Cameroon Gynecology and Obstetrics Unit Central Hospital of Yaound Yaound Cameroon Womens Health Program Cameroon Baptist Convention Health Services Yaound Cameroon Department of Obstetrics and Gynaecology Gyneco-Obstetric and Pediatric Hospital of Yaound Yaound Cameroon Expanded Program of Immunization Ministry of Health Yaound Cameroon Department of Obstetrics and Gynaecology Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital Yaounde Cameroon Department of Obstetrics and Gynaecology University of Dschang Dschang Cameroon Higher Institute of Medical Technology Nkolondom Yaound Cameroon

Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between february 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a

关键词： High-Risk Human Papillomavirus Precancerous Digital Cervicography VIA/VILI Serotype

The transcriptional landscape of the developmental switch from regular pollen maturation towards microspore-derived plant regeneration in barley

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The Crop Journal 2024年第4期12卷 1064-1080页

作者： Anna Nowicka Martin Kovacik Anna Maksylewicz Przemysław Kopec Ewa Dubas Monika Krzewska Agnieszka Springer robert E.Hoffie Diaaeldin S.Daghma Zbynek Milec Ales Pecinka Jochen Kumlehn Iwona Zur The franciszek Górski Institute of Plant Physiology Polish Academy of Sciences Niezapominajek 2130-239 KrakówPoland Institute of Experimental Botany of the Czech Academy of Sciences Centre of Plant Structural and Functional GenomicsŠlechtitelu3177900 OlomoucCzech Republic Department of Cell Biology and Genetics Faculty of SciencePalacky UniversityŠlechtitelu°2777900 OlomoucCzech Republic Malopolska Centre of Biotechnology Jagiellonian University30-387 KrakówPoland Leibniz Institute of Plant Genetics and Crop Plant Research(IPK)Gatersleben Corrensstraße 306466 Stadt SeelandGermany Institute for Breeding Research on Horticultural Crops Julius Kühn Institute(JKI)-Federal Research Centre for Cultivated PlantsErwin-Baur Straße 2706484 QuedlinburgGermany Global Change Research Institute Czech Academy of Sciences Beˇlidla 986/4a60300 BrnoCzech Republic

Plant formation from in vitro-cultivated microspores involves a complex network of internal and environmental ***/doubled haploids(DHs)derived from in vitro-cultured microspores are widely used in plant breeding and genetic ***,the mechanism underlying the developmental switch from regular pollen maturation towards microspore-derived plant regeneration remains poorly ***,RNA-sequencing was employed to elucidate the transcriptional landscapes of four early stages of microspore embryogenesis(ME)in barley cultivars Golden Promise and Igri,which exhibit contrasting responsiveness to microspore-derived plant *** experiments revealed fundamental regulatory networks,specific groups of genes,and transcription factor(Tf)families potentially regulating the developmental *** identified a set of candidate genes crucial for genotype-dependent responsiveness/recalcitrance to *** high-resolution temporal transcriptome atlas provides an important resource for future functional studies on the genetic control of microspore developmental transition.

关键词： Hordeum vulgare Marker gene Microspore embryogenesis Stress response Transcriptome analysis

Anosov and expanding attractors

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Science China Mathematics 2020年第9期63卷 1929-1934页

作者： robert f.Williams Department of Mathematics University of Texas at AustinAustinTX 78705USA Institute for Advanced Study PrincetonNJ 08540USA

An earlier conjecture is settled with an immersion of a 2-dimensional branched *** obstructions in linear algebra and tiling theory are studied rst.

关键词： Anosov expanding attractor Cantor set ber bundle