The genome of Lespedeza potaninii reveals biased subgenome evolution and drought adaptation.

Lespedeza potaninii, a xerophytic subshrub belonging to the legume family, is native to the Tengger Desert and is highly adapted to drought. It has important ecological value due to its drought adaptability, but the underlying molecular mechanisms remain largely unknown. Here, we report a 1.24 Gb chromosome-scale assembly of the L. potaninii genome (contig N50 = 15.75 Mb). Our results indicate that L. potaninii underwent an allopolyploid event with 2 subgenomes, A and B, presenting asymmetric evolution and B subgenome dominance. We estimate that the 2 diploid progenitors of L. potaninii diverged around 3.6 million years ago (MYA) and merged around 1.0 MYA. We revealed that the expansion of hub genes associated with drought responses, such as the binding partner 1 of accelerated cell death 11 (ACD11) (BPA1), facilitated environmental adaptations of L. potaninii to desert habitats. We found a novel function of the BPA1 family in abiotic stress tolerance in addition to the known role in regulating the plant immune response, which could improve drought tolerance by positively regulating reactive oxygen species homeostasis in plants. We revealed that bZIP transcription factors could bind to the BPA1 promoter and activate its transcription. Our work fills the genomic data gap in the Lespedeza genus and the tribe Desmodieae, which should provide theoretical support both in the study of drought tolerance and in the molecular breeding of legume crops.

Identifying miRNA-mRNA Pairs and Novel miRNAs from Hepatocelluar Carcinoma miRNomes and TCGA Database.

Increasing evidence shows microRNAs (miRNAs) are engaged in hepatocelluar carcinoma (HCC). To identify novel feasible miRNA/mRNA pairs involved in hepatocarcinogenesis, an in-depth analysis of miRNomes in human non-tumor liver and HCC samples was carried out in this study. Firstly, differentially expressed miRNAs were obtained from deep sequencing of 15 liver samples, and verified in an independent data from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed mRNA targets were selected from TCGA, and the differential miRNA/mRNA pairs with negative correlations were screened out. Finally, functional enrichment analysis was used to predict the functions of miRNA/mRNA pairs in HCC. In our study, 81 miRNA/mRNA pairs and 7 novel miRNAs were found. We constructed a hub interaction model with 9 miRNA/mRNA pairs to further investigate molecular mechanism of HCC. Survival analysis identified nine genes (hsa-miR-137, hsa-miR-490, BIRC5, TOP2A, CDC25C, IGF2BP1, IQGAP3, NCAPG and VIPR1) with significant influence on prognosis of HCC patients. In conclusion, the miRNA/mRNA pairs identified in our study may have some potential values to be further studied in progression, diagnosis and prognosis of HCC.

Role of Granulocyte-colony Stimulating Factor in the Protection of Cerebral Vascular Endothelium, White Matter, and Cognition.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has protective effects on many neurological diseases. The effects of G-CSF on vascular endothelium and White Matter (WM) injury in Cerebral Small Vessel Disease (CSVD) were explored in this study via a model of spontaneously hypertensive rat (SHR) in order to elucidate the mechanism of G-CSF in Vascular Cognitive Impairment (VCI). METHODS: 24-week-old male SHRs were randomly divided into the treatment group and model group, with the same age Wistar rats as the control group. The novel object recognition test (NORT) and Morris water maze were conducted after 7 days of G-CSF(50ug/kg) or normal saline treatment to examine their non-spatial and spatial cognitive functions. After that, a transmission electron microscope (TEM) and FLB staining were used to observe the vascular endothelial cell and WM damage. Furthermore, the expression of VEGF, MMP-9, Caspase-3, TUNEL and BrdULaminin in the cortical area was detected by immunostaining methods. RESULTS: Our results showed that G-CSF promoted the expression of VEGF and BrdU+-Laminin+ endothelial cells, but down-regulated the level of MMP-9, thus significantly repaired the cerebral vascular endothelial cells and perivascular structure in SHR. The WM damage, the expression of caspase-3 and the apoptosis rate decreased after G-CSF treatment. Ultimately, G-CSF improved the non-spatial cognitive function in SHR rather than the spatial cognitive function. CONCLUSION: Therefore, our findings indicated that G-CSF might facilitate the improvement of non-spatial cognitive function in CSVD by repairing endothelial cells and alleviating WM damage.

Association between alcoholic interventions and abstinence rates for alcohol use disorders: A meta-analysis.

OBJECTIVE: The aim of present study is to quantitatively evaluate the association between different interventions and abstinence rates based on network meta-analysis. METHOD: Following PRISMA guidelines, randomized clinical trials that compared different alcoholic interventions for alcohol use disorders associated with abstinence rates in treatment sessions or/and follow-up sessions were recruited. Main data synthesis was performed by Bayesian random-effects network meta-analyses, and the relative ranking of interventions was estimated by cumulative probability P values (SUCRA). Funnel plot symmetry was used to detect publication bias. Moreover, pair-wised comparison was also conducted to determine the statistical difference and forest plots were generated to calculate the differences between the groups. The Grades of Recommendations Assessment, Development and Evaluation (GRADE) criteria were utilized for the recommendations of evidence from pairwise direct comparisons. RESULTS: A total of 137 RCTs containing 27,282 participants and 8 variations of psychotherapy, pharmacotherapy, contingency management, and brief intervention used as treatment interventions were included. In summary, contingency management plus psychotherapy was demonstrated to be effective and possessed the best rank of achieving the highest abstinence rate in treatment sessions (SUCRA, 0.61). Pharmacotherapy plus psychotherapy also revealed its efficacy and was associated with the highest abstinence rate in follow-up sessions (SUCRA, 0.40). More importantly, psychotherapy alone was demonstrated not to be associated with higher abstinence rates in both treatment (OR, 1.052; 95% CI, 0.907-1.220) and follow-up sessions (OR, 0.967; 95% CI, 0.552-1.693), yet pharmacotherapy seemed to be the only intervention associated with higher abstinence rates compared to controls in both sessions (treatment session: OR, 1.074; 95% CI, 1.002-1.152) (follow-up session: OR, 1.442; 95% CI, 1.094-1.900). CONCLUSIONS: Contingency management plus psychotherapy and pharmacotherapy plus psychotherapy were demonstrated to be associated with the highest abstinence rates in treatment sessions and follow-up sessions, respectively. However, contingency management and pharmacotherapy seemed to be the substantial crucial factors allowing for the maintenance of the highest abstinence rates in respective sessions, although we need more evidence for further validation.

Granulocyte Colony-Stimulating Factor Attenuates Blood-Brain Barrier Damage and Improves Cognitive Function in Spontaneously Hypertensive Rats.

BACKGROUND: Cerebral small vessel diseases (CSVDs) always coincide with endothelial dysfunction and blood-brain barrier (BBB) damage. However, the detailed mechanisms of CSVD are still unclear and the therapeutic efficacy is not so satisfaction. Granulocyte-colony stimulating factor (G-CSF) can play a neuroprotective role in many neurological diseases. We investigated whether G-CSF exerted positive effects on BBB protection and cognitive function improvement in spontaneously hypertensive rats (SHRs), a rat model displaying the early histopathological changes of CSVD. METHOD: Twenty-four-week-old SHRs received daily administrations of either G-CSF (50µg/kg) or normal saline (NS) for 7 days. The novel object recognition test (NORT) was then conducted after treatment. After behavioral test, we examined IgG fluorescence staining to indicate BBB leakage. G-CSF receptor (G-CSFR), aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression were determined by immunofluorescence. The surface structure of endothelial cells was examined by scanning electron microscopy (SEM). RESULTS: G-CSF significantly attenuated IgG leakage and improved non-spatial memory in SHRs. G-CSFR was expressed at higher levels in both G-CSF-SHRs and NS-SHRs. The surface structural changed on the endothelial cells and expression of AQP-4 and GFAP decreased after G-CSF treatment. However, no significant differences in Claudin-5 expression were observed. CONCLUSION: These findings demonstrated that the administration of exogenous G-CSF can improve cognitive function in a model of CSVD, possibly due to the recovery of endothelial and BBB function.