Ruixue Ai

• Zhang, Yimeng; Zhu, Shuyang; Li, Yixuan; Tan, Xiangrong; Liu, Zhiyuan & Tang, Hua [Vis alle 9 forfattere av denne artikkelen] (2026). Dynamic Multimodal Routing With Drones Under Communication Uncertainty in Emergency Logistics: A Hybrid Reinforcement Learning–Heuristic Approach. IET Intelligent Transport Systems. ISSN 1751-956X. 20(1), s. 1–20. doi: 10.1049/itr2.70302. Fulltekst i vitenarkiv
• Pan, Junping; Wang, Ping-Jie; Zhang, Jianying; Knapskog, Anne-Brita; Watne, Leiv Otto & Wang, He-Ling [Vis alle 40 forfattere av denne artikkelen] (2026). Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology. Nature Aging. 6(5), s. 1079–1102. doi: 10.1038/s43587-026-01108-z. Fulltekst i vitenarkiv
• Lin, Jin Yi; Huang, Ze Bo; Zhang, Shi-qi; Wu, Yong; Cheng, Ling Jun & Gao, Xiangzheng [Vis alle 17 forfattere av denne artikkelen] (2026). STUB1-VCP/p97 complex regulates mitophagy via fine-tuning of PINK1 levels. Cell reports. 45(4). doi: 10.1016/j.celrep.2026.117183. Fulltekst i vitenarkiv
• Li, Bailei; Ai, Ruixue; Chen, Xinjiani; Wang, Yaning; Pan, Chenlei & Song, Suxian [Vis alle 15 forfattere av denne artikkelen] (2025). Multiscale Design of Dental Restorative Materials: Mechanistic Foundations, Technological Innovations, and Clinical Translation. Advanced Science. 12(48). doi: 10.1002/advs.202511258. Fulltekst i vitenarkiv Vis sammendrag

  Dental restorative materials remain constrained by clinical unmet needs in biomechanical durability, bioactivity, and long-term tissue integration, despite incremental advances in conventional ceramics and polymers. Addressing these gaps requires functional innovation. Multiscale design strategies bridge atomic-level material engineering with macroscopic clinical performance. This review highlights transformative approaches, including bioinspired architectures (e.g., decellularized extracellular matrix scaffolds) that replicate native oral tissue mechanics while promoting cell-driven remodeling, and smart interfaces (e.g., pH-responsive polymers) for dynamic biofilm suppression. Functional enhancements are achieved via 3D printing for anatomically precise restorations, nanotechnology for crack-resistant ceramics, and surface functionalization (e.g., graphene oxide coatings) to accelerate osseointegration. Emerging paradigms such as 4D-printed shape-memory composites and artificial intelligence (AI)-driven inverse design further exemplify innovation by enabling self-adapting materials and accelerated discovery of bioactive formulations. Critically, barriers are analyzed to clinical translation, including scalable manufacturing of hierarchical structures, mitigating biodegradation in aggressive oral environments, and balancing cost-effectiveness with performance. By integrating mechanistic insights with clinical translation, this work provides a blueprint for next-generation functional dental materials that reconcile laboratory innovation with real-world clinical demands.

• Li, Ling; Pan, Dan; Ai, Ruixue & Zhou, Yu (2025). Mitochondria-Associated Pathways in Cancer and Precancerous Conditions: Mechanistic Insights. International Journal of Molecular Sciences. ISSN 1661-6596. 26(17). doi: 10.3390/ijms26178537. Fulltekst i vitenarkiv Vis sammendrag

  Mitochondria perform critical roles in cellular functions, particularly in metabolism and cell death regulation. Mutations in nuclear and mitochondrial genes can cause mitochondrial dysfunction, leading to classical mitochondrial diseases. Emerging evidence suggests that mitochondrial adaptations in cancer support the high energy demands of proliferating cells and contribute to tumor progression through anti-apoptotic mechanisms, dysregulated mitochondrial quality control (mtQC), and altered mitochondrial DNA (mtDNA) copy numbers. Interestingly, several mitochondrial pathways involved in cancer progression resemble those implicated in mitochondrial diseases. From this perspective, although cancer is not a classical mitochondrial disease, its progression involves mitochondria-associated pathways similar to those in mitochondrial disorders, suggesting that cancer may be considered a mitochondria-related disease in a broader sense. Understanding these shared mechanisms could provide new insights into precision treatment strategies. Furthermore, mitochondrial dysfunction is increasingly recognized in precancerous conditions, suggesting its potential as a target for early intervention. Oral potentially malignant disorders (OPMDs) serve as a valuable model for studying these mitochondria-associated mechanisms, offering a promising avenue for both therapeutic advancements and preventive approaches.

• He, Haijun; Ai, Ruixue; Fang-Stavem, Fei & Palikaras, Konstantinos (2025). The Rab3 family proteins in age-related neurodegeneration: unraveling molecular pathways and potential therapeutic targets. npj Aging. 11(1). doi: 10.1038/s41514-025-00257-6. Fulltekst i vitenarkiv
• Pan, Dan; Wang, Jiongke; Cai, Luyao; Huang, Mei; Han, Qi & Zheng, Zhijian [Vis alle 10 forfattere av denne artikkelen] (2025). Pyodermatitis–Pyostomatitis Vegetans: The Role of Langerin Deficiency in Disease Pathogenesis. Journal of Clinical Medicine. 14(12). doi: 10.3390/jcm14124198. Fulltekst i vitenarkiv Vis sammendrag

  Background/Objectives: Pyodermatitis–pyostomatitis vegetans (PPV) is a rare, chronic inflammatory mucocutaneous disorder. However, the etiology of PPV remains controversial. Methods: A review of online PPV case studies from PubMed, Wanfang database, Web of Science, and books has been performed. Comparative analysis of langerin expression has been conducted to verify the hypothesis summarized from the literature review by Immunohistochemistry (IHC). Results: A total of 63 patients were analyzed across 5 reviews, 44 case reports, and 1 book chapter. Our findings revealed distinct immunological alterations in PPV patients. Innate immunity was upregulated, marked by increased neutrophil and eosinophil counts and enhanced macrophage activity. Adaptive immunity was suppressed, with reduced dendritic cell (DC) numbers and activity and diminished adaptive immune responses. We hypothesize that langerin was a critical factor, contributing to adaptive immune suppression and a compensatory innate immune hyperactivation. Conclusions: We propose the hypothesis that langerin expression on Langerhans cells (LCs) plays a pivotal role in PPV pathogenesis by shifting the immune balance toward innate hyperactivation at the expense of adaptive immunity.

• Ai, Ruixue; Mao, Lipeng; Jin, Xurui; Campos-Marques, Carlos; Zhang, Shi-qi & Pan, Junping [Vis alle 33 forfattere av denne artikkelen] (2025). NAD+ reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C. Science Advances. 11(45). doi: 10.1126/sciadv.ady9811. Fulltekst i vitenarkiv Vis sammendrag

  Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer’s disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD+) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD+ enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD+ augmentation corrects the ASEs of many genes via a key protein, EVA1C (epithelial V-like antigen 1 homolog C), which is involved in neuronal development and activities. EVA1C is reduced in the hippocampus in patients with AD compared to cognitively normal ones. NAD+-induced memory retention is partially dependent on EVA1C, as adeno-associated virus–based Eva1c knockdown in the hippocampal CA1 region annuls NAD+-induced memory improvement in pathological Tau–bearing mice. We propose that NAD+ reduces AD pathologies, at least partially, via amplification of the NAD+-EVA1C splicing axis, pointing to a potential splice-switching therapy for AD.

• Cai, Luyao; Mao, Fei; Huang, Xiaoyu; Li, Dan; Pan, Dan & Hu, Yuting [Vis alle 11 forfattere av denne artikkelen] (2025). The potential contribution of metal dyshomeostasis to the occurrence of oral leukoplakia-through abnormal immune function. Metallomics. ISSN 1756-5901. 17(12). doi: 10.1093/mtomcs/mfaf041. Fulltekst i vitenarkiv
• Ai, Ruixue; Xiao, Xianglu; Deng, Shenglong; Yang, Nan; Xing, Xiaodan & Watne, Leiv [Vis alle 16 forfattere av denne artikkelen] (2025). Artificial intelligence in drug development for delirium and Alzheimer's disease. Acta Pharmaceutica Sinica B (APSB). ISSN 2211-3835. 15(9), s. 4386–4410. doi: 10.1016/j.apsb.2025.04.026. Fulltekst i vitenarkiv
• Wang, Wenwen; Huang, Jiani; Qian, Shuangjie; Zheng, Yi; Yu, Xinyue & Jiang, Tao [Vis alle 13 forfattere av denne artikkelen] (2024). Amyloid-β but not tau accumulation is strongly associated with longitudinal cognitive decline. CNS Neuroscience & Therapeutics. ISSN 1755-5930. 30(7). doi: 10.1111/cns.14860. Fulltekst i vitenarkiv Vis sammendrag

  Objective Alzheimer's disease (AD) pathology is featured by the extracellular accumulation of amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles in the brain. We studied whether Aβ and tau accumulation are independently associated with future cognitive decline in the AD continuum. Methods Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public database. A total of 1272 participants were selected based on the availability of Aβ-PET and CSF tau at baseline and of those 777 participants with follow-up visits. Results We found that Aβ-PET and CSF tau pathology were related to cognitive decline across the AD clinical spectrum, both as potential predictors for dementia progression. Among them, Aβ-PET (A + T− subjects) is an independent reliable predictor of longitudinal cognitive decline in terms of ADAS-13, ADNI-MEM, and MMSE scores rather than tau pathology (A − T+ subjects), indicating tau accumulation is not closely correlated with future cognitive impairment without being driven by Aβ deposition. Of note, a high percentage of APOE ε4 carriers with Aβ pathology (A+) develop poor memory and learning capacity. Interestingly, this condition is not recurrence in terms of the ADNI-MEM domain when adding APOE ε4 status. Finally, the levels of Aβ-PET SUVR related to glucose hypometabolism more strongly in subjects with A + T− than A − T+ both happen at baseline and longitudinal changes. Conclusions In conclusion, Aβ-PET alone without tau pathology (A + T−) measure is an independent reliable predictor of longitudinal cognitive decline but may nonetheless forecast different status of dementia progression. However, tau accumulation alone without Aβ pathology background (A − T+) was not enough to be an independent predictor of cognitive worsening.

• Mao, Fei; Cai, Luyao; Pan, Dan; Huang, Mei; Wang, Qing & Chen, Qianming [Vis alle 8 forfattere av denne artikkelen] (2024). Burning Mouth Syndrome May Essentially Be Related To Psychoneuroimmunology: Mechanism Hypothesis. Journal of Oral Rehabilitation. ISSN 0305-182X. 52(2), s. 199–207. doi: 10.1111/joor.13893. Fulltekst i vitenarkiv
• Angelucci, Francesco; Ai, Ruixue; Piendel, Lydia; Cerman, Jiri & Hort, Jakub (2024). Integrating AI in fighting advancing Alzheimer: diagnosis, prevention, treatment, monitoring, mechanisms, and clinical trials. Current Opinion in Structural Biology. ISSN 0959-440X. 87. doi: 10.1016/j.sbi.2024.102857. Fulltekst i vitenarkiv
• Qian, Shuangjie; He, Haijun; Xiong, Xi; Ai, Ruixue; Wang, Wenwen & Zhu, Huimin [Vis alle 10 forfattere av denne artikkelen] (2023). Identification of mitophagy-associated proteins profile as potential plasma biomarkers of idiopathic Parkinson's disease. CNS Neuroscience & Therapeutics. ISSN 1755-5930. 00, s. 1–14. doi: 10.1111/cns.14532. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy‐associated proteins (MAPs), including PTEN‐induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated‐TBK1 (p‐TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD. Methods The study population comprised 116 age‐matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs. Results MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p‐TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1‐Parkin levels and prominent diagnostic accuracy in A‐synuclein (+) subjects than in A‐synuclein (−) subjects. Conclusions These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.

• Li, Bailei; Xu, Jiren; Ai, Ruixue; Zhang, Haixing; Wei, Mingjun & Zhang, Rongqing [Vis alle 8 forfattere av denne artikkelen] (2023). Safe and Durable Treatment of Dentin Hypersensitivity via Nourishing and Remineralizing Dentin Based on β-Chitooligosaccharide Graft Derivative. Small. ISSN 1613-6810. 19(41). doi: 10.1002/smll.202300359. Fulltekst i vitenarkiv
• Xie, Chenglong; Zhuang, Xu-Xu; Niu, Zhangming; Ai, Ruixue; Lautrup, Sofie Hindkjær & Zheng, Shuangjia [Vis alle 29 forfattere av denne artikkelen] (2022). Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nature Biomedical Engineering. 6(1), s. 76–93. doi: 10.1038/s41551-021-00819-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.

• Naranjo-Galindo, Francisco José; Ai, Ruixue; Fang, Evandro Fei; Nilsen, Hilde Loge & SenGupta, Tanima (2022). C. elegans as an Animal Model to Study the Intersection of DNA Repair, Aging and Neurodegeneration. Frontiers in Aging. 3. doi: 10.3389/fragi.2022.916118. Fulltekst i vitenarkiv Vis sammendrag

  Since its introduction as a genetic model organism, Caenorhabditis elegans has yielded insights into the causes of aging. In addition, it has provided a molecular understanding of mechanisms of neurodegeneration, one of the devastating effects of aging. However, C. elegans has been less popular as an animal model to investigate DNA repair and genomic instability, which is a major hallmark of aging and also a cause of many rare neurological disorders. This article provides an overview of DNA repair pathways in C. elegans and the impact of DNA repair on aging hallmarks, such as mitochondrial dysfunction, telomere maintenance, and autophagy. In addition, we discuss how the combination of biological characteristics, new technical tools, and the potential of following precise phenotypic assays through a natural life-course make C. elegans an ideal model organism to study how DNA repair impact neurodegeneration in models of common age-related neurodegenerative diseases.

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• Ai, Ruixue & Fang-Stavem, Fei (2025). NAD+ restores proteostasis through splicing-dependent autophagy. Autophagy. ISSN 1554-8627. 22(2), s. 436–438. doi: 10.1080/15548627.2025.2596679. Fulltekst i vitenarkiv Vis sammendrag

  Autophagy preserves neuronal integrity by clearing damaged proteins and organelles, but its efficiency declines with aging and neurodegeneration. Depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) is a hallmark of this decline, yet how metabolic restoration enhances autophagic control has remained obscure. Meanwhile, alternative RNA splicing errors accumulate in aging brains, compromising proteostasis. Here, we identify a metabolic – transcriptional mechanism linking NAD+ metabolism to autophagic proteostasis through the NAD+ -EVA1C axis. Cross-species analyses in C. elegans, mice, and human samples reveal that NAD+ supplementation corrects hundreds of age- or Alzheimer-associated splicing errors, notably restoring balanced expression of EVA1C isoforms. Loss of EVA1C impairs the memory and proteostatic benefits of NAD+, underscoring its essential role in neuronal resilience. Mechanistically, NAD+ rebalances EVA1C isoforms that interact with chaperones BAG1 and HSPA/HSP70, reinforcing their network to facilitate chaperone-assisted selective macroautophagy and proteasomal degradation of misfolded proteins such as MAPT/tau. Thus, NAD+ restoration coordinates RNA splicing fidelity with downstream proteostatic systems, establishing a metabolic – transcriptional checkpoint for neuronal quality control. This finding expands the paradigm of autophagy regulation, positioning metabolic splice-switching as a crucial mechanism to maintain proteostasis and suggesting new strategies to combat aging-related neurodegenerative diseases.

• Ai, Ruixue; Xu-Xu, Zhuang; Anisimov, Aleksander; Lu, Jia-Hong & Fang, Fei (2022). A synergized machine learning plus cross-species wet-lab validation approach identifies neuronal mitophagy inducers inhibiting Alzheimer disease. Autophagy. ISSN 1554-8627. 18(4), s. 939–941. doi: 10.1080/15548627.2022.2031382. Fulltekst i vitenarkiv
• Meron, Esther; Thaysen, Maria; Angeli, Suzanne; Antebi, Adam; Barzilai, Nir & Baur, Joseph A. [Vis alle 78 forfattere av denne artikkelen] (2022). Meeting Report: Aging Research and Drug Discovery. Aging. 14(2), s. 530–543. doi: 10.18632/aging.203859. Fulltekst i vitenarkiv Vis sammendrag

  Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year’s 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.

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