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Therapeutic advances in neural regeneration for Huntington’s disease

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Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia lombardozzi Fabrizio Ammannito Annamaria Cimini michele d’Angelo Department of life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to o

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

Frequency stabilization of C-band semiconductor lasers through a SiN photonic integrated circuit

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Photonics Research 2024年第8期12卷 1619-1626页

作者： AlESSANDRO BRUGNONI AlI EMRE KAPlAN VAlERIO VITAlI KYlE BOTTRIll michele RE PERIKlIS PETROPOUlOS COSIMO lACAVA IlARIA CRISTIANI Photonics Group Department of ElectricalComputer and Biomedical EngineeringUniversity of PaviaPavia 27100Italy Optoelectronics Research Centre University of SouthamptonSouthampton SO171BJUK Huawei Technologies Italia S.r.l Centro direzionale MilanoSegrate 20054Italy

Integrated semiconductor lasers represent essential building blocks for integrated optical components and circuits and their stability in frequency is fundamental for the development of numerous frontier applications and engineering *** dense optical circuits are considered,the stability of integrated laser sources can be impaired by the thermal cross-talk generated by the action of neighboring components,leading to a deterioration of the long-term system performance(on the scale of seconds).In this work we show the design and the experimental characterization of a silicon nitride photonic integrated circuit(PIC)that is able to frequency stabilize 16semiconductor lasers,simultaneously.A stabilized 50 GHz-spaced two-channel system is demonstrated through the detection of the related beating note and the stability of the resulting waveform is characterized via the use of artificially induced thermal cross-talk stimuli.

关键词： stabilization stability impaired

中华医学会-欧莱雅中国人健康皮肤/毛发研究项目成果总结——皮肤篇

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中华皮肤科杂志 2024年第5期57卷 464-467页

作者： michele Verschoore 牛悦青 Stéphane Commo léopold Muller 魏宇昊甄雅贤刘玮欧莱雅研发和创新中心法国克里希92110 欧莱雅研发和创新中心上海201206 欧莱雅研发和创新中心法国欧奈苏布瓦93600 欧莱雅研发和创新中心美国克拉克07066 空军特色医学中心皮肤科北京100142

中华医学会和欧莱雅集团在2003-2018年间联合启动了“中国人健康皮肤/毛发研究项目”,该项目在助力提高中国皮肤科医生科研能力的同时,获得了大量宝贵的基于中国人群样本的临床和基础研究成果,并以期刊论文、会议报告等形式多次参与国... 详细信息

中华医学会和欧莱雅集团在2003-2018年间联合启动了“中国人健康皮肤/毛发研究项目”,该项目在助力提高中国皮肤科医生科研能力的同时,获得了大量宝贵的基于中国人群样本的临床和基础研究成果,并以期刊论文、会议报告等形式多次参与国内和国际学术交流。本文作者通过整理项目资料和已发表文献,对皮肤相关研究项目的主要成果做一总结.

关键词：皮肤生理学过程皮肤衰老皮肤色素沉着皮肤免疫研究报告

Supervised vs home-based exercise program in kidney transplant recipients: A pilot pragmatic non-randomized study

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World Journal of Transplantation 2024年第4期14卷 123-132页

作者： Anna Crepaldi Giovanni Piva Nicola lamberti michele Felisatti luca Pomidori Yuri Battaglia Fabio Manfredini Alda Storari Pablo Jesús lópez-Soto Unit of Nephrology University Hospital of FerraraFerrara 44121Emilia-RomagnaItaly Department of Nursing Instituto Maimónides de Investigación Biomédica de CórdobaCordoba 14004AndalusiaSpain Department of Neuroscience and Rehabilitation University of FerraraFerrara 44121Emilia-RomagnaItaly Esercizio Vita Medical Fitness Ferrara 44124Emilia-RomagnaItaly Department of Medicine University of VeronaVerona 37100VenetoItaly Department of Nursing Maimonides Biomedical Research Institute of CordobaUniversity of CordobaReina Sofía University HospitalCordoba 14004AndalusiaSpain

BACKGROUND Although the benefits of exercise for kidney transplant recipients(KTRs)have been widely demonstrated,these patients experience several barriers in undertaking a structured exercise program in hospital and non-hospital *** To compare the effects of a supervised moderate-intensity gym-based intervention with a home-based low-intensity walking program on exercise capacity in *** KTRs were asked to choose between two six-month *** first group performed a low-intensity interval walking intervention at home-based exercise intervention (HBex). The second group performed a supervised training program at an adapted physical activitygym (Sgym), including aerobic and resistance training. The outcomes, collected at baseline and at the end of theprograms, included the 6-minute walking test, the peak oxygen consumption (VO_(2)peak) during a treadmill test,the 5-time sit-to-stand test, and blood *** patients agreed to participate and self-selected into the HBex (n = 9) and Sgym (n = 8) groups. Twopatients in the Sgym group dropped out because of familial problems. At baseline, patients in the HBex group weresignificantly older and had lower walking distance, VO_(2)peak, and lower limb strength. Primary outcome changeswere significantly greater in the HBex group than in the Sgym group (52 ± 23 m vs 8 ± 34;P = 0.005). No othersignificant differences between groups were observed. Both groups improved most of the outcomes in the withingroupcomparisons, with significant variations in VO_(2) ***-month moderate-intensity supervised or low-intensity home-based training programs effectively improvedexercise capacity in KTRs. Gym-based programs combine aerobic and resistance training;however, in-homewalking may be proposed for frail KTRs.

关键词： Exercise Transplantation Walking Training Nephrology Kidney disease

Homocysteinemia and Depression in Community-Dwelling Older Adults: The Cohort longitudinal Study “InveCeAb” (Brain Aging in Abbiategrasso)

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Health 2024年第1期16卷 22-36页

作者： Mauro Colombo Annalisa Davin Elena Rolandi michele Rossi Riccardo Ferrari Erica Spina Antonio Guaita Golgi Cenci Foundation Abbiategrasso Italy

Depression is a major health problem, especially for elderly people. According to the “homocysteine hypothesis of depression”, high homocysteine levels may cause depression of mood via cerebrovascular diseases. Whilst biologically plausible, such hypothesis needs yet confirmation. We aimed at: 1) studying the relationships between homocysteinemia (HCY) and depression in a community-dwelling cohort of people aged 70 to 75 years at baseline;2) investigating plasma levels of HCY and 3) comparing these levels between males and females, in the same population. We exploited the data from four waves (2010, 2012, 2014 and 2018) of the longitudinal study “InveCeAb”, with specific regard towards mood assessment, by Geriatric Depression Scale (GDS) scoring, and diagnosis of clinically relevant or subthreshold depression. HCY plasma levels were measured in the waves 2012, 2014 and 2018. Sample attrition was due mainly to death or overall worsening. No statistically significant differences were found in plasma homocysteine levels in each wave, according to depressive symptoms. No correlations were found between plasma HCY levels in each wave with their corresponding GDS scores, even after adjustment for folate and cobalamin blood concentrations. Dichotomized levels of HCY (≤15 vs >15 μM/l) were not associated with dichotomized GDS scores (≤4 vs higher), clinically relevant and subthreshold depression diagnosis and any antidepressive use, in any wave. First (2012) HCY levels increased with participants’ increasing age, cross-sectionally. listwise HCY concentrations decreased along the 3 waves. HCY levels were always higher in males than in females. Our results may challenge the “homocysteine hypothesis” of depression, whilst supporting the role of high homocysteinemia as a marker of overall bad health.

关键词： Homocysteinemia Depression Aging Cohort

Thermodynamics and dielectric response of BaTiO_(3)by data-driven modeling

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npj Computational Materials 2022年第1期8卷 1998-2014页

作者： lorenzo Gigli Max Veit michele Kotiuga Giovanni Pizzi Nicola Marzari michele Ceriotti laboratory of Computational Science and Modeling(COSMO) Institute of MaterialsÉcole Polytechnique Fédérale de LausanneCH-1015LausanneSwitzerland Theory and Simulation of Materials(THEOS)and National Centre for Computational Design and Discovery of Novel Materials(MARVEl) École Polytechnique Fédérale de LausanneCH-1015LausanneSwitzerland

Modeling ferroelectric materials from first principles is one of the successes of density-functional theory and the driver of much development effort,requiring an accurate description of the electronic processes and the thermodynamic equilibrium that drive the spontaneous symmetry breaking and the emergence of macroscopic *** demonstrate the development and application of an integrated machine learning model that describes on the same footing structural,energetic,and functional properties of barium titanate(BaTiO_(3)),a prototypical *** model uses ab initio calculations as a reference and achieves accurate yet inexpensive predictions of energy and polarization on time and length scales that are not accessible to direct ab initio *** predictions allow us to assess the microscopic mechanism of the ferroelectric *** presence of an order-disorder transition for the Ti off-centered states is the main driver of the ferroelectric transition,even though the coupling between symmetry breaking and cell distortions determines the presence of intermediate,partly-ordered ***,we thoroughly probe the static and dynamical behavior of BaTiO_(3)across its phase diagram without the need to introduce a coarse-grained description of the ferroelectric ***,we apply the polarization model to calculate the dielectric response properties of the material in a full ab initio manner,again reproducing the correct qualitative experimental behavior.

关键词： transition ferroelectric dielectric

The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

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Bone Research 2016年第2期4卷 85-90页

作者： Qian Zhang michele Doucet Ryan E Tomlinson Xiaobin Han l Darryl Quarles Michael T Collins Thomas l Clemens Department of Orthopaedic Surgery Johns Hopkins University Baltimore MD USA Department of Medicine University of Tennessee Health Science Center Memphis TN USA Skeletal Clinical Studies Unit craniofacial and Skeletal Diseases Branch National Institutes of HealthBethesda MD USA Baltimore Veterans Administration Medical Center Baltimore MD USA

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-la inhibitors decreased HIF-la and FGF23 protein accumulation and inhibited HIF-la-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-la consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-la inhibitor. These results show for the first time that HIF-la is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-la activity in TIO contributes to the aberrant FGF23 production in these patients.

关键词： The hypoxia-inducible factor-1 activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia HIF

Compact n-Manifolds via(n+l)-Colored Graphs:a New Approach

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Algebra Colloquium 2020年第1期27卷 95-120页

作者： luigi Grasselli michele Mulazzani Dipartimcnto di Scicnze e Metodi dell'Ingegneria Universita di Modena e Reggio Emilia Via Giovanni Amendola2-Pad.Morselli 42122 Reggio EmiliaItaly Dipartimento di Matematica and ARCES Universita di Bologna Piazza di Porta San Donato 540126 BolognaItaly

We introduce a representation via(n+l)-colored graphs of compact n-manifolds with(possibly empty)boundary,which appears to be very convenient for computer aided study and *** construction is a generalization to arbitrary dimension of the one recently given by Cristofori and Mulazzani in dimension three,and it is dual to the one given by Pezzana in the *** this context we establish some results concerning the topology of the represented manifolds:suspensions,fundamental groups,connected sums and moves between graphs representing the same *** results of compact orientable 4-manifolds representable by graphs up to six vertices are obtained,together with some properties of the G-degree of 5-colored graphs relating this approach to tensor models theory.

关键词： compact manifolds colored graphs fundamental groups dipole moves

Covariation between plant biodiversity and soil systems in a European beech forest and a black pine plantation:the case of Mount Faito,(Campania,Southern Italy)

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Journal of Forestry Research 2022年第1期33卷 239-252页

作者： Tiziana Danise michele Innangi Elena Curcio Antonietta Fioretto Department of Environmental Biological and Pharmaceutical Sciences and TechnologiesUniversity of Campania“Luigi Vanvitelli”Via Vivaldi 4381100 CasertaItaly

Both climate and land-use changes,including the introduction and spread of allochthonous species,are forecast to affect forest ***,forests will be affected in terms of species composition as well as their soil chemical and biological *** possible changes in both tree cover and soil system might impact the amount of carbon that is stored in living plants and dead biomass and within the soil ***,such alterations can have a strong impact on the detrital food web that is linked to litter *** there are studies on the infuence of plant diversity on soil physical and chemical characteristics,the effects on soil biological activity and carbon storage processes remain largely *** aim of this study was to investigate and compare chemical and biological variables in covariation with plant communities in an autochthonous beech forest(Fagus sylvatica l.)and a black pine plantation(Pinus nigra *** ***).Our results confirmed that the two communities were considerably different,with the old-growth beech community having a lower number of plant species and the pine community was in development as a consequence of anthropogenic *** aspects of the two communities were also refected in the soil,with the beech soil having higher nitrogen levels and a more specialized microbial community compared to the pine soil,with most extracellular enzymes(such as peroxidase and chitinase)showing lower activity in the pine soil.

关键词： 2B-PlS Plant and soil Vegetation Soil enzymes