Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.
Alzheimer Disease , Lipid Metabolism , Parkinson Disease , Humans , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Lipid Metabolism/drug effects , Lipid Metabolism/physiology , Parkinson Disease/metabolism , Parkinson Disease/drug therapy , Animals
Cisplatin is a common anticancer drug able to kill tumor cells, but it causes adverse reactions in the kidney, digestive tract, and other systems. The antitumor effects of cisplatin are mainly due to its ability to bind to the DNA in tumor cells to prevent replication, thereby reducing RNA and protein syntheses, leading to cell damage and death. Cisplatin has a wide range of applications; it can be used to treat cervical, thyroid, ovarian, and other cancers. Cisplatin has a beneficial therapeutic effect, but its therapeutic selectivity is poor. In addition to eliminating diseased target cells, cisplatin can damage normal cells; in women of reproductive age being treated for cancer, cisplatin can lead to ovarian function impairment, premature ovarian failure (POF), and/or infertility. Therefore, reducing the adverse effects of cisplatin on ovarian function is an important topic in clinical research. In this paper, we explore the research progress on the POF caused by cisplatin treatment.
Migration models have evolved significantly during the last decade, most notably the so-called flow Fixed-Effects (FE) gravity models. Such models attempt to infer how human mobility may be driven by changing economy, geopolitics, and the environment among other things. They are also increasingly used for migration projections and forecasts. However, recent research shows that this class of models can neither explain, nor predict the temporal dynamics of human movement. This shortcoming is even more apparent in the context of forced migration, in which the processes and drivers tend to be heterogeneous and complex. In this article, we derived a Flow-Specific Temporal Gravity (FTG) model which, compared to the FE models, is theoretically similar (informed by the random utility framework), but empirically less restrictive. Using EUROSTAT data with climate, economic, and conflict indicators, we trained both models and compared their performances. The results suggest that the predictive power of these models is highly dependent on the length of training data. Specifically, as time-series migration data lengthens, FTG's predictions can be increasingly accurate, whereas the FE model becomes less predictive.
Climate , Gravitation , Humans
Objective: To explore the global research trends and hotspots of steroid-induced osteonecrosis of the femoral head (SONFH) through qualitative and quantitative analysis of bibliometrics. Methods: All publications on SONFH published from 1992 to 2021 were extracted from the Web of Science Core Collection database. CiteSpace was used for the visualization analysis of major countries, active institutions, productive authors, and the burst of keywords. VOSviewer was used for coupling analysis of countries/regions, institutions, and authors. Microsoft Excel 2017 was used for statistical analysis, drawing bar charts, pie charts, and cumulative area charts. The software of MapInfo was used to draw the distribution map of the publications. Results: A total of 780 publications were included for analyses. The most productive year was 2020 with 98 records. China was the most influential country with 494 publications, an H-index of 59, and total citations of 16820. The most prolific institution was Shanghai Jiaotong University in China with 53 publications and 998 citations. Clinical Orthopaedics and Related Research (IF = 4.755, 2021) was the most active journal with 26 articles. The hot keywords were "osteonecrosis", "avascular necrosis", "osteogenic differentiation", "proliferation", "PPAR gamma", "apoptosis", "oxidative stress", "genetic polymorphism" and "mesenchymal stem cells". The keywords like "proliferation", "PPAR gamma" and "genome-wide" have emerged in recent years. Conclusion: The number of publications in SONFH has increased significantly in the last three decades. The pathologic mechanism of SONFH gathered most research interests. Genomics and cell molecular biology of SONFH are the research frontiers.
Femur Head , Peroxisome Proliferator-Activated Receptors , Humans , China , Bibliometrics , Steroids
Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.
Arabidopsis , Animals , Arabidopsis/metabolism , Embryonic Development , Humans , RNA Precursors/genetics , RNA Precursors/metabolism , RNA Splicing/genetics , Ribonucleoprotein, U2 Small Nuclear/genetics , Ribonucleoprotein, U2 Small Nuclear/metabolism , Saccharomyces cerevisiae/metabolism , Zebrafish/genetics , Zebrafish/metabolism
Abscisic acid (ABA) is an important phytohormone regulating plant growth, development and stress responses. A multitude of key factors implicated in ABA signaling have been identified; however, the regulation network of these factors needs for further information. AtS40.4, a plant-specific DUF584 domain-containing protein, was identified previously as a senescence regulator in Arabidopsis. In this study, our finding showed that AtS40.4 was negatively involved in ABA signaling during seed germination and early seedling growth. AtS40.4 was highly expressed in seeds and seedlings, and the expression level was promoted by ABA. AtS40.4 was localized both in the nucleus and the cytoplasm. Moreover, the subcellular localization pattern of AtS40.4 was affected by ABA. The knockdown mutants of AtS40.4 exhibited an increased sensitivity to ABA, whereas the overexpression of AtS40.4 decreased the ABA response during seed germination and seedling growth of Arabidopsis. Furthermore, AtS40.4 was involved in ABRE-dependent ABA signaling and influenced the expression levels of ABA INSENTIVE (ABI)1-5 and SnRK2.6. Further genetic evidence demonstrated that AtS40.4 functioned upstream of ABI4. These findings support the notion that AtS40.4 is a novel negative regulator of the ABA response network during seed germination and early seedling growth.
Flowering is a critical stage of plant development and is closely correlated with seed production and crop yield. Flowering transition is regulated by complex genetic networks in response to endogenous and environmental signals. FLOWERING LOCUS C (FLC) is a central repressor in the flowering transition of Arabidopsis thaliana. The regulation of FLC expression is well studied at transcriptional and post-transcriptional levels. A subset of antisense transcripts from FLC locus, collectively termed cold-induced long antisense intragenic RNAs (COOLAIR), repress FLC expression under cold exposure. Recent studies have provided important insights into the alternative splicing of COOLAIR and FLC sense transcripts in response to developmental and environmental cues. Herein, at the 20th anniversary of FLC functional identification, we summarise new research advances in the alternative splicing of FLC sense and antisense transcripts that regulates flowering.
