Increased level of RAB39B leads to neuronal dysfunction and behavioural changes in mice.

Duplications of the Xq28 region are a common cause of X-linked intellectual disability (XLID). The RAB39B gene locates in Xq28 and has been implicated in disease pathogenesis. However, whether increased dosage of RAB39B leads to cognitive impairment and synaptic dysfunction remains elusive. Herein, we overexpressed RAB39B in mouse brain by injecting AAVs into bilateral ventricles of neonatal animals. We found that at 2 months of age, neuronal overexpression of RAB39B impaired the recognition memory and the short-term working memory in mice and resulted in certain autism-like behaviours, including social novelty defect and repetitive grooming behaviour in female mice. Moreover, overexpression of RAB39B decreased dendritic arborization of primary neurons in vitro and reduced synaptic transmission in female mice. Neuronal overexpression of RAB39B also altered autophagy without affecting levels and PSD distribution of synaptic proteins. Our results demonstrate that overexpression of RAB39B compromises normal neuronal development, thereby resulting in dysfunctional synaptic transmission and certain intellectual disability and behavioural abnormalities in mice. These findings identify a molecular mechanism underlying XLID with increased copy numbers of Xq28 and provide potential strategies for disease intervention.

Genetic mapping reveals BjRf as a candidate gene controlling fertility restoration of the oxa CMS in Brassica juncea.

KEY MESSAGE: A candidate gene for male fertility restoration in Brassica juncea, BjRf, was isolated from a 23-kb interval on chromosome A05 using map-based cloning and BSA methods. The cytoplasmic male sterility/fertility restoration (CMS/Rf) system has been extensively used for heterosis in plants. It also provides valuable resources for studying mitochondrial-nuclear coevolution and interaction. The oxa CMS, which is a new CMS type reported in Brassica juncea (B. juncea), has been broadly used in the exploitation and application of heterosis in this species. However, the oxa CMS fertility restorer gene BjRf has not been reported. In this study, a stable restorer line was successfully constructed via continuous testcross and artificial selection. Besides, a new Rf gene was mapped in a 23-kb region on chromosome A05 in B. juncea with a genetic distance of 0.5 cM by the method incorporating bulk segregant analysis (BSA) and conventional map-based cloning. Finally, BjuA017917, a non-PPR Rf gene encoding a guanosine nucleotide diphosphate dissociation inhibitor (GDI), is proposed to be the candidate gene for fertility restoration of the oxa CMS line in B. juncea. Moreover, a functional marker, CRY3, was developed for marker-assisted selection for Brassica juncea breeding.

Fine-mapping of the BjPur gene for purple leaf color in Brassica juncea.

Purple leaves are rich in health-protecting anthocyanins and food colorants in Brassica juncea. But the causal gene, which is related to leaf color formation, have not been reported in B. juncea. Anthocyanins mainly accumulated throughout the adaxial and abaxial epidermal leaf cells of purple leaves. A genetic analysis indicated that an incompletely dominant gene controls the purple leaf trait in B. juncea. Furthermore, the BjPur gene, which increased anthocyanin accumulation in purple-leaf mustard, was cloned. Blast and phylogenetic analyses revealed that BjPur encodes a new R2R3-MYB transcription factor. Sequence analysis of two alleles revealed a DNA sequence insertion in the first intron of BjPur in green leaves parent line (LY) when compared with the BjPur gene in the purple-leaf parent line (ZY). And this insertion greatly reduced the transcription of BjPur in green leaves. In purple-leaf plants, the transcript level of BjPur was significantly higher in leaves than in roots, stems, siliques, and flower buds. Additionally, molecular markers linked to leaf color were developed to distinguish different genotypes of B. juncea. These results will be helpful for the genetic improvement of the purple leaf color in B. juncea.

Machine Learning Algorithm for Predicting Distant Metastasis of T1 and T2 Gallbladder Cancer Based on SEER Database.

(1) Background: This study seeks to employ a machine learning (ML) algorithm to forecast the risk of distant metastasis (DM) in patients with T1 and T2 gallbladder cancer (GBC); (2) Methods: Data of patients diagnosed with T1 and T2 GBC was obtained from SEER, encompassing the period from 2004 to 2015, were utilized to apply seven ML algorithms. These algorithms were appraised by the area under the receiver operating characteristic curve (AUC) and other metrics; (3) Results: This study involved 4371 patients in total. Out of these patients, 764 (17.4%) cases progressed to develop DM. Utilizing a logistic regression (LR) model to identify independent risk factors for DM of gallbladder cancer (GBC). A nomogram has been developed to forecast DM in early T-stage gallbladder cancer patients. Through the evaluation of different models using relevant indicators, it was discovered that Random Forest (RF) exhibited the most outstanding predictive performance; (4) Conclusions: RF has demonstrated high accuracy in predicting DM in gallbladder cancer patients, assisting clinical physicians in enhancing the accuracy of diagnosis. This can be particularly valuable for improving patient outcomes and optimizing treatment strategies. We employ the RF algorithm to construct the corresponding web calculator.

NF-κB pathway play a role in SCD1 deficiency-induced ceramide de novo synthesis.

Stearoyl-CoA-desaturase 1 (SCD1) deficiency mediates apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis. The mechanisms underlying the cross-talk between SCD1 and ceramide synthesis have not been explored. We treated colorectal cancer cells with an SCD1 inhibitor and examined the effects on gene expression, cell growth, and cellular lipid contents. The main effect of SCD1 inhibition on the fatty acid contents of colorectal cancer cells was a decrease in monounsaturated fatty acids (MUFAs). RNA sequencing (RNA-seq) showed that the most intense alteration of gene expression after SCD1 inhibition occurred in the NF-κB signaling pathway. Further experiments revealed that SCD1 inhibition resulted in increased levels of phosphorylated NF-κB p65 and increased nuclear translocation of NF-κB p65. Treatment with an NF-κB inhibitor eliminated several effects of SCD1 inhibition, mainly including overexpression of serine palmitoyltransferase1 (SPT1), elevation of dihydroceramide contents, and suppression of cell growth. Furthermore, treatment with supplemental oleate counteracted the SCD1-induced NF-κB activation and downstream effects. In summary, our data demonstrate that the NF-κB pathway plays a role in SCD1 deficiency-induced ceramide de novo synthesis in colorectal cancer cells, and that reduced MUFA levels contribute to the course.

RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.

RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson's disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. In the present study, we established Rab39b knockout (KO) mice, which exhibited overall normal birth rate and morphologies as wild type mice. However, Rab39b deficiency led to reduced anxiety and impaired learning and memory in 2 months old mice. Deletion of Rab39b resulted in impairments of synaptic structures and functions, with reductions in NMDA receptors in the postsynaptic density (PSD). RAB39B deficiency also compromised autophagic flux at basal level, which could be overridden by rapamycin-induced autophagy activation. Further, treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice, without affecting the PSD distribution of NMDA receptors. Together, these results suggest that RAB39B plays an important role in regulating both autophagy and synapse formation, and that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations.

Dental fluorosis of children aged 8-12 in diseased areas in Xi an City from 2014 to 2018 / 中国学校卫生

Objective@#To evaluate the dynamic prevalence of dental fluorosis of children and levels of fluoride in drinking water after improvement of water in Xi an City, to provide scientific basis for water fluoridation improvement.@*Methods@#A total of 35 fluorosis endemic villages were selected as fixed monitor sites in 2014-2018, the ways of water improvement were surveyed, water fluorine content were detected and the prevalence of dental fluorosis in children aged 8 to 12 years were examined.@*Results@#Rates of excess fluoride in drinking water from 2014 to 2018 were 22.86%, 14.29%,11.43%, 11.43% and 8.57%, the difference were significant(χ2=16.44, P<0.01).The dental fluorosis detection rates of children aged 8 to 12 years were 20.89%,18.22%,17.46%,18.13% and 16.76% in 2014-2018 which showed a obvious descending trend by year(χ2=10.02, P<0.01). The detection rate of dental fluorosis in children aged 8 and 9 years showed a decreasing trend by year(χ2=6.53, 4.54, P<0.05).The difference of total rate of dental fluorisis,rate of mild cases rate of moderate-to-severe cases were statistically between the villages without qualified water and the villages with normal fluorine water(χ2=179.22, 167.93,10.35, P<0.01). The rate of detection in the villages with the water fluorine exceed standard in 2014-2018 showed a declining trend year by year(χ2=28.50, P<0.01). The detection rate were significant different across water improvement methods(χ2=197.76, P<0.01). Detection rate of dental fluorosis decreased from 2014 to 2018 in the areas with municipal water supply showed a decreasing after year(χ2=12.16, P<0.01).@*Conclusion@#The improvement of municipal water supply shows significant effects on water fluorosis control, the detection rate of water fluoride and children s dental fluorosis in some villages with the other ways of water improvement are still higher than expected, the continuously monitor of fluoride content in water and dental fluorosis in children should be strengthened.