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spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： Benjamin r.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg school of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALs2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions sPAsT spastin

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scalable Ir‑Doped NiFe_(2)O_(4)/TiO_(2)Heterojunction Anode for Decentralized saline Wastewater Treatment and H_(2)Production

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Nano-Micro Letters 2025年第3期17卷 1-18页

作者： sukhwa Hong Jiseon Kim Jaebeom Park sunmi Im Michael r.Hoffmann Kangwoo Cho Division of Environmental science and Engineering Pohang University of Science and Technology(POSTECH)Pohang 790−784Korea Linde Laboratory California Institute of TechnologyPasadenaCA 91125USA Institute for Convergence research and Education in Advanced Technology(I‑CrEATE) Yonsei University International CampusIncheon 21983Republic of Korea

Wastewater electrolysis cells(WECs)for decentralized wastewater treatment/reuse coupled with H_(2)production can reduce the carbon footprint associated with transportation of water,waste,and energy *** study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2)overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment *** dilute(0.1 M)NaCl solutions,the NFI/TiO_(2)marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).robust operation in near-neutral pH was *** including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for Cl−chemisorption and a protective layer for NFI as an ohmic *** electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive *** scaled-up WEC with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.

关键词： Wastewater electrolysis cell Ir-doped NiFe_(2)O_(4) reactive chlorine species Decentralized H_(2)production On-site wastewater treatment

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Pathophysiology and treatment of Barrett's esophagus

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World Journal of Gastroenterology 2010年第30期16卷 3762-3772页

作者： Daniel s Oh steven r DeMeester Department of surgery The University of Southern CaliforniaKeck School of MedicineLos AngelesCA 90033United States

Gastroesophageal reflux disease (GErD) affects an estimated 20% of the population in the United states. About 10%-15% of patients with GErD develop Barrett’s esophagus, which can progress to adenocarcinoma, currently the most prevalent type of esophageal cancer. The esophagus is normally lined by squamous mucosa, therefore, it is clear that for adenocarcinoma to develop, there must be a sequence of events that result in transformation of the normal squamous mucosa into columnar epithelium. This sequence begins with gastroesophageal reflux, and with continued injury metaplastic columnar epithelium develops. This article reviews the pathophysiology of Barrett’s esophagus and implications for its treatment. The effect of medical and surgical therapy of Barrett’s esophagus is compared.

关键词： Gastroesophageal reflux disease Barrett’s esophagus Lower esophageal sphincter Esophageal motility Proton pump inhibitors Antireflux surgery

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semantic segmentation of Lumbar Vertebrae Using Meijering U-Net(MU-Net)on spine Magnetic resonance Images

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Computer Modeling in Engineering & sciences 2025年第1期142卷 733-757页

作者： Lakshmi s V V shiloah Elizabeth Darmanayagam sunil retmin raj Cyril Department of Computer science and Engineering College of Engineering GuindyAnna UniversityChennai600025India Department of Information Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower back pain is one of the most common medical problems in the world and it is experienced by a huge percentage of people *** to its ability to produce a detailed view of the soft tissues,including the spinal cord,nerves,intervertebral discs,and vertebrae,Magnetic resonance Imaging is thought to be the most effective method for imaging the *** semantic segmentation of vertebrae plays a major role in the diagnostic process of lumbar *** is difficult to semantically partition the vertebrae in Magnetic resonance Images from the surrounding variety of tissues,including muscles,ligaments,and intervertebral discs.U-Net is a powerful deep-learning architecture to handle the challenges of medical image analysis tasks and achieves high segmentation *** work proposes a modified U-Net architecture namely MU-Net,consisting of the Meijering convolutional layer that incorporates the Meijering filter to perform the semantic segmentation of lumbar vertebrae L1 to L5 and sacral vertebra ***-colour mask images were generated and used as ground truth for training the *** work has been carried out on 1312 images expanded from T1-weighted mid-sagittal MrI images of 515 patients in the Lumbar spine MrI Dataset publicly available from Mendeley *** proposed MU-Net model for the semantic segmentation of the lumbar vertebrae gives better performance with 98.79%of pixel accuracy(PA),98.66%of dice similarity coefficient(DsC),97.36%of Jaccard coefficient,and 92.55%mean Intersection over Union(mean IoU)metrics using the mentioned dataset.

关键词： Computer aided diagnosis(CAD) magnetic resonance imaging(MrI) semantic segmentation lumbar vertebrae deep learning U-Net model

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Nucleoside modified mrNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural regeneration research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal Nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural regeneration research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CArIM-school for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma sciences research University of BirminghamEdgbastonBirminghamUK MHeNs-school for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(csVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term csVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CsVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

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Combinatorial therapies for spinal cord injury repair

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Neural regeneration research 2025年第5期20卷 1293-1308页

作者： Carla s.sousa Andreia Monteiro António J.salgado Nuno A.silva Life and Health sciences research Institute(ICVs) School of MedicineUniversity of MinhoCampus de Gualtar-gualtarBragaPortugal ICVs/3B’s Associate Lab PT Government Associated LabCampus de Gualtar-gualtarBragaPortugal

spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

关键词： electric stimulation neural tissue regeneration neuroprotection polytherapy spinal cord injury

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Predicting Maximum Lifespan Limits at Mean Menopausal Age

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Journal of Mathematical research with Applications 2025年第1期 133-142页

作者： M.sUMATHI s.ANTONY CArLA Department of Mathematics N.M.S.S.Vellaichamy Nadar College research scholar (Part-time) Madurai Kamaraj University

The age at which a woman enters natural menopause has also been associated to death from any cause. Menopause is a natural component of aging that happens between the ages of 45 and 55, with the average menopausal age being 51. Previous research has revealed the age at which women reach menopause, but there is no evidence to support the link between menopause and longevity. We made a study in assessing the limits of maximum lifespan at menopausal age in our previous article. In this paper, we aim to predict the maximum lifespan of women at mean menopausal age.

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A mild, configurable, flexible CoNi-LDH（v）/Zn battery based on H-vacancy-induced reversible Zn2+ intercalation

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Journal of Energy Chemistry 2025年第1期100卷 498-508页

作者： Xinyue Cheng Dingsheng Wu Hao Gao Qingqing Wang Pengfei Lv sam s.Yoon Qufu Wei Key Laboratory of Eco-textiles Ministry of Education Jiangnan University school of Mechanical Engineering Korea University

Flexible Zn-based batteries have attracted increasing research interest as essential components of wearable energy storage ***,the advancement of flexible aqueous Zn-based batteries based on Co-Ni layered double hydroxide （CoNi-LDH） as the cathode material is hampered by their poor cycling stability and the corrosiveness of alkaline ***,CoNi-LDH nanosheets enriched with H vacancies (CoNi-LDH（v）) were constructed on a flexible carbon cloth （CC） substrate via electrochemical deposition and *** Zn-based battery comprising CoNi-LDH（v）@CC as the cathode exhibited highly reversible conversion reactions and stable operation in 3 M ZnsO4electrolyte （pH=4）.The battery delivered an excellent specific capacity (225 mA h g-1,0.26 mA h cm-2),acceptable cycling stability（53.9%,900 cycles）,and high discharging *** abundant H vacancies served as active sites for the reversible intercalation of Zn2+and the extravasation of NO3-generated channels and space for Zn2+transport and storage,together enabling an excellent Zn2+storage ***,a sandwich-structured solid-state CoNi-LDH（v）@CC//Zn@CC battery was fabricated and was found to exhibit a noteworthy electrochemical performance and mechanical *** a proof of concept,the unencapsulated battery powered a digital watch under various deformation conditions and operated stably for 80 ***,the flexible battery displayed outstanding customizability,maintaining an open-circuit voltage of 1.42 V even after being cut *** proposed engineering strategy contributes to the realization of textiles with truly wearable energy-storage devices.

关键词： CoNi/Zn battery H vacancies Mild aqueous electrolyte Tailorable battery Wearable energy storage device

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Elevated basal intestinal mucosal cytokine levels in asymptomatic first-degree relatives of patients with Crohn's disease

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World Journal of Gastroenterology 2000年第1期6卷 49-52页

作者： Indaram AVK Nandi s Weissman s Lam s Bailey B Blumstein M Greenberg r Bank s Division of Gastroenterology Long Island Jewish Medical CenterAlbert Einstein College of MedicineNew YorkUSA

AIM To determine levels of cytokines incolonic mucosa of asymptomatic first degreerelatives of Crohn’s disease *** Cytokines(Interleukin(IL)1-Beta,IL-2,IL-5 and IL-8)were measured using ELIsAin biopsy samples of normal looking colonicmucosa of first degree relatives of Crohn’sdisease patients(n = 9)and from normalcontrols(n = 10)with no family history ofCrohn’s *** Asymptomatic first degree relativesof patients with Crohn’s disease had significantlyhigher levels of basal intestinal mucosalcytokines(IL-2,IL-5 and IL-8)than *** these increased cytokinelevels serve as phenotypic markers for a geneticpredisposition to developing Crohns diseaselater on,or whether they indicate early(pre-clinical)damage has yet to be further *** Asymptomatic first degreerelatives of Crohn’s disease patients have higherlevels of cytokines in their normal-lookingintestinal mucosa compared to normal controls,This supports the hypothesis that increasedcytokines may be a cause or an early event inthe inflammatory cascade of Crohns disease andare not merely a result of the inflammatoryprocess.

关键词： subject headings crohns disease cytokine/analysis intestinal mucosa

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