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Objective To analyze the incidence and influencing factors of acute adverse reactions (AARs) of non-ionic iodine contrast medium (ICM) in the real world. Methods A retrospective case-control study was carried out on 332 683 patients receiving ICM-enhanced CT examination at our medical center from 2014 to 2020. They were 184 498 males and 148 185 females, at an age from 0 to 101 (57.91±14.36) years. According to experiencing AARs or not, the patients were divided into case group (ICM-AARs, n=931) and control group (no ICM-AARs, n=331 752). Single factor and multi factor logistic regression analyses were used to screen out the influencing factors of ICM-AARs. Results In the cohort, the incidence of ICM-AARs was 0.28% (931/332 683), with mild, moderate and severe AARs accounted for 93.88%, 4.83% and 1.29%, respectively. The results of regression analysis showed that history of ICM adverse reactions (OR=22.881, 95%CI: 16.235~32.246), history of other allergies (OR=4.406, 95%CI: 2.338~8.303) and asthma (OR=5.614, 95%CI: 2.596~12.138) were closely associated with the occurrence of ICM-AARs (P < 0.05). Gender, source, history of drug allergy, ICM type and injection speed were risk factors, while older age, history of ICM use and hypertension history were protective factors (OR=0.396~1.674, P < 0.05), but the strengths of above associations with the ICM-AARs were relatively weak (P < 0.05). Conclusion The incidence of ICM-AARs is 0.28%, mainly mild adverse reactions. Previous history of ICM adverse reactions, other allergies, and asthma are the main factors affecting the occurrence of ICM-AARs.

Microglia play a pivotal role in the coordination of brain development and have emerged as a critical determinant in the progression of neurodegenerative diseases; however, the role of microglia in the onset and progression of neurodevelopmental disorders is less clear. Here we show that conditional deletion of αVβ8 from the central nervous system (Itgb8ΔCNS mice) blocks microglia in their normal stepwise development from immature precursors to mature microglia. These "dysmature" microglia appear to result from reduced TGFβ signaling during a critical perinatal window, are distinct from microglia with induced reduction in TGFβ signaling during adulthood, and directly cause a unique neurodevelopmental syndrome characterized by oligodendrocyte maturational arrest, interneuron loss, and spastic neuromotor dysfunction. Consistent with this, early (but not late) microglia depletion completely reverses this phenotype. Together, these data identify novel roles for αVβ8 and TGFβ signaling in coordinating microgliogenesis with brain development and implicate abnormally programmed microglia or their products in human neurodevelopmental disorders that share this neuropathology.

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.

The study of functional traits and their relationship to trade-offs has provided valuable insights into how plants adapt to environmental changes. Nonetheless, further research is necessary to fully comprehend the subtropical montane trade-off patterns in moss functional traits and the impact of environmental gradients on the correlation of these traits. To address this gap, we conducted a study of 11 moss species (7 families, 9 genera) in 54 patches from two subtropical mountain ranges, examining 40 functional traits related to photosynthesis, nutrients, water retention, and architecture. Through principal component analysis (PCA) and bi-variate correlation analysis, our findings reveal a strong correlation between light capture and nutrient assimilation strategies, as evidenced by the coordination between the traits of light capture and nutrient per area along a main principal component. Interestingly, we observed a trend towards smaller leaves and leaf cells in species with higher capacity for photosynthesis and metabolism, consistent with global trait spectra in vascular plants. However, we found that the trade-off between light capture and nutrient assimilation strategies was independent of water-holding capacity at shoot levels. Instead, we found that water-holding capacity was closely associated with nutrient utilization, energy metabolism, chlorophyll synthesis, and the primary process of photosynthesis. Our results highlight the multiple dimensions of functional traits in subtropical montane mosses and demonstrate that variation in these traits is driven by water availability, slope, and canopy density. Overall, our study provides valuable insights into the co-variation of moss traits and how environmental changes may impact mosses and ecosystem function. [ABSTRACT FROM AUTHOR]

Over 30% of patients with amyotrophic lateral sclerosis (ALS) exhibit cognitive deficits indicative of frontotemporal dementia (FTD), suggesting a common pathogenesis for both diseases. Consistent with this hypothesis, neuronal and glial inclusions rich in TDP43, an essential RNA-binding protein, are found in the majority of those with ALS and FTD, and mutations in TDP43 and a related RNA-binding protein, FUS, cause familial ALS and FTD. TDP43 and FUS affect the splicing of thousands of transcripts, in some cases triggering nonsense-mediated mRNA decay (NMD), a highly conserved RNA degradation pathway. Here, we take advantage of a faithful primary neuronal model of ALS and FTD to investigate and characterize the role of human up-frameshift protein 1 (hUPF1), an RNA helicase and master regulator of NMD, in these disorders. We show that hUPF1 significantly protects mammalian neurons from both TDP43- and FUS-related toxicity. Expression of hUPF2, another essential component of NMD, also improves survival, whereas inhibiting NMD prevents rescue by hUPF1, suggesting that hUPF1 acts through NMD to enhance survival. These studies emphasize the importance of RNA metabolism in ALS and FTD, and identify a uniquely effective therapeutic strategy for these disorders.

Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (Bdnf) as a target of FUS-R521C-associated DNA damage and RNA splicing defects in mice. Compared with WT FUS, mutant FUS-R521C proteins formed a more stable complex with Bdnf RNA in electrophoretic mobility shift assays. Stabilization of the FUS/Bdnf RNA complex contributed to Bdnf splicing defects and impaired BDNF signaling through receptor TrkB. Exogenous BDNF only partially restored dendrite phenotype in FUS-R521C neurons, suggesting that BDNF-independent mechanisms may contribute to the defects in these neurons. Indeed, RNA-seq analyses of FUS-R521C spinal cords revealed additional transcription and splicing defects in genes that regulate dendritic growth and synaptic functions. Together, our results provide insight into how gain-of-function FUS mutations affect critical neuronal functions.