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• A review of the adoption of generative adversarial networks in clinical neuroimaging. • We focus on GAN's applications in modeling disease effects of neurologic diseases. • We discuss the pitfalls of current studies and provide future perspectives. Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to the broader family of generative methods, which learn to generate realistic data with a probabilistic model by learning distributions from real samples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review critically appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) is one of the most potent therapeutic targets for osteoarthritis (OA). We identified that miR-654-3p protected the phenotype of chondrocytes. We demonstrated that TNF receptor superfamily member 9 (TNFRSF9) was the target of miR-654-3p by binding to its 3′UTR regions, based on a dual-luciferase reporter assay and an RNA binding protein immunoprecipitation (RIP) assay. In addition, further experiments proved that TNFRSF9, as a trigger of the NF-κB pathway, correlated with the inflammation in chondrocytes. MiR-654-3p overexpressed in the knee of mice alleviated the OA in vivo. Moreover, we examined the m6A enzyme level in OA, proving that the abnormal expression of α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) contributed to the miR-654-3p decrease. Our research illustrated the significant role of miR-654-3p in OA, including its maturation and the mechanism in protecting the phenotype of chondrocytes, which could be a new treatment target for OA. • miR-654-3p decreased the inflammation in OA by targeting TNFRSF9 directly. • TNFRSF9 activated the NF-κB Pathway in OA which could be suppressed by CD137 protein. • Excessive ALKBH5 limited the maturation of miR-654-3p. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. However, the AD mechanism has not yet been fully elucidated to date, hindering the development of effective therapies. In our work, we perform a brain imaging genomics study to link genetics, single-cell gene expression data, tissue-specific gene expression data, brain imaging-derived volumetric endophenotypes, and disease diagnosis to discover potential underlying neurobiological pathways for AD. To do so, we perform brain-wide genome-wide colocalization analyses to integrate multidimensional imaging genomic biobank data. Specifically, we use (1) the individual-level imputed genotyping data and magnetic resonance imaging (MRI) data from the UK Biobank, (2) the summary statistics of the genome-wide association study (GWAS) from multiple European ancestry cohorts, and (3) the tissue-specific cis-expression quantitative trait loci (cis-eQTL) summary statistics from the GTEx project. We apply a Bayes factor colocalization framework and mediation analysis to these multi-modal imaging genomic data. As a result, we derive the brain regional level GWAS summary statistics for 145 brain regions with 482,831 single nucleotide polymorphisms (SNPs) followed by posthoc functional annotations. Our analysis yields the discovery of a potential AD causal pathway from a systems biology perspective: the SNP chr10:124165615:G>A (rs6585827) mutation upregulates the expression of BTBD16 gene in oligodendrocytes, a specialized glial cells, in the brain cortex, leading to a reduced risk of volumetric loss in the entorhinal cortex, resulting in the protective effect on AD. We substantiate our findings with multiple evidence from existing imaging, genetic and genomic studies in AD literature. Our study connects genetics, molecular and cellular signatures, regional brain morphologic endophenotypes, and AD diagnosis, providing new insights into the mechanistic understanding of the disease. Our findings can provide valuable guidance for subsequent therapeutic target identification and drug discovery in AD. [ABSTRACT FROM AUTHOR]

Paleolithic rock paintings are known from many parts of the world, including Africa, Australia, Europe and Island Southeast Asia. However, no Paleolithic rock paintings have yet been confirmed in the East Asia mainland, partly due to the lack of suitable dating materials. The rock paintings distributed at more than 70 sites in the Jinsha River valley, Yunnan Province, southwestern China, include the naturalistic outlines of large mammals, which superficially resemble the Magdalenian rock art in Europe. Wanrendong Cave in Tiger Leaping Gorge, has preserved typical Jinsha River rock paintings, associated with some precipitates of secondary carbonates (i.e., speleothem). High precision U-series dating of 13 small speleothems, with a total of 36 subsamples overlying or underlying the pigment layers, revealed that these red paintings were created during the Pleistocene – Holocene transition, representing the oldest absolutely dated rock paintings from China so far. Our results show that at least three painting phases in Wanrendong Cave can be precisely constrained: ∼13,000–13,580 yr B.P., ∼10,540–10,830 yr B.P., and ∼8370–8700 yr B.P. These intervals are substantially earlier than the timing of agriculture in Yunnan Province (∼4600 yr BP), indicating that these paintings were created by Paleolithic hunter-gatherers. Additionally, these intervals coincide with the Bølling-Allerød and early Holocene warming periods, suggesting a possible link between the rock painting activity and climate changes. • High-precision U-series dating was applied to the speleothems associated with the rock paintings in Wanrendong Cave. • Wanrendong rock paintings were dated to three phases: 1) ∼13,000–13,580 yr B.P., 2) ∼10,540–10,830 yr B.P., and 3) ∼8370–8700 yr B.P. • The ages of Wanrendong rock paintings indicate that these paintings were created by Paleolithic hunter-gatherers. [ABSTRACT FROM AUTHOR]