To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used LC-MS/MS to construct a large-scale comparative proteome profile of human placentas from normal and preeclamptic pregnancies. A total of 2636 proteins were detected in human placentas, and 171 different proteins were definitively identified between control and preeclamptic placentas. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes which occur during pathological changes of preeclamptic placenta. 6 proteins were randomly selected to verify their expression patterns with Western blotting. Of which, 3 proteins’ cellular localizations were validated with immunohistochemistry. Elucidation of how protein-expression changes coordinate the pathological development would provide researchers with a better understanding of the critical biological processes of preeclampsia and potential targets for therapeutic agents to regulate placenta function, and eventually benefit the treatment of preeclampsia.

Objective: A limited number of studies have previously reported on the regional activity [amplitude of low-frequency fluctuation (ALFF)] and functional integration [functional connectivity (FC)] of the whole brain in deficit schizophrenia (DS). The present study investigates the resting-state characteristics of the fractional ALFF (fALFF) and the FC in both DS and non-deficit schizophrenia (NDS) patients, and further explores their correlations with neurocognitive features. Methods: Demographic, resting-state functional magnetic resonance imaging (MRI), and neurocognitive data were collected from 33 DS and 41 NDS male patients, as well as in 40 male healthy controls (HCs). The voxel-wise fALFF was measured to evaluate regional cerebral function. Regions with differences in fALFF between DS and NDS patients were used as seed points in whole-brain FC analysis. Partial correlation analysis was conducted to examine associations between the fALFF or the FC of altered regions and neurocognitive assessments. Results: Both patient groups showed decreased fALFF in the sensorimotor area, visual cortex, and frontoparietal pathway, but increased fALFF in the precuneus and middle cingulate gyrus when compared with the HCs. Moreover, the NDS group demonstrated higher fALFF than HCs in the left thalamus, caudate, and hippocampus. Compared with the NDS group, the fALFF of the visual cortex was specifically increased, but that of the bilateral insula, the anterior cingulate gyrus (ACG), and the regions extended to the frontotemporal cortex was decreased in the DS group. Numerous abnormal FCs of nerve pathways were found between the two patient groups, mainly concentrated in the frontooccipital, frontotemporal, insula-visual cortex, as well as the temporooccipital pathway. Correlation analysis indicated that, in the DS group, the FC value between the left insula and the visual cortex was positively correlated with cognitive flexibility. In the NDS group, the fALFF of the right insula was negatively correlated with speech fluency, and the FC value between the ACG and the visual cortex was positively correlated with visual spatial memory. Conclusion: The present study demonstrates different altered patterns of fALFF and FC between male patients with DS and NDS. The specific altered regions of the salience network (SN) associated with impaired neurocognition in male DS patients suggest novel insights into the pathogenesis of cognitive impairment in schizophrenia.

BackgroundChronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. The major challenges for current therapies are the low efficacy of current drugs and the occurrence of drug resistant HBV mutations. RNA interference (RNAi) of virus-specific genes offers the possibility of developing a new anti-HBV therapy. Recent reports have shown that lentiviral vectors based on HIV-1 are promising gene delivery vehicles due to their ability to integrate transgenes into non-dividing cells. Herein, a lentivirus-based RNAi system was developed to drive expression and delivery of HBV-specific short hairpin RNA (shRNA) in a mouse model for HBV replication.MethodsHepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the sera of the mice were analyzed by quantitative sandwich enzyme linked immunosorbent assay (ELISA) technique, hepatitis B core antigen (HBcAg) and HBsAg in the livers of the mice were detected by immunohistochemical assay, HBV DNA and HBV mRNA were measured by fluorogenic quantitative polymerase chain reaction (FQ-PCR) and quantitative real-time PCR respectively.ResultsCo-injection of HBV plasmids together with the lentivirus targeting HBV shRNA induced an RNAi response. Secreted HBsAg was reduced by 89% in mouse serum, and HBeAg was also significantly inhibited, immunohistochemical detection of HBcAg or HBsAg in the liver tissues also revealed substantial reduction. Lentiviral mediated shRNA caused a significant suppression in the levels of viral mRNA and DNA synthesis compared to the control group.ConclusionLentivirus-based RNAi can be used to suppress HBV replication in vivo, it might become a potential therapeutic strategy for treating HBV and other viral infections.

The function of zfp91 is mainly studied in vitro, but there is no study in vivo. Accumulative data suggest that zfp91 may be an important gene to regulate all aspects of human response. However, there are no data to date about the function of zfp91 on cardiac homeostasis. Thus, we aimed to observe the role of zfp91 gene in mouse cardiomyocytes on myocardial homeostasis and related mechanisms under pressure overload. In the study, zfp91 mRNA and protein levels were significantly reduced in TAC‐operated WT mice as compared with controls. Genetic ablation of zfp91 dramatically led to pathological cardiac dysfunction and hypertrophy after transverse aortic constriction (TAC). Adenosine A1 receptor (Adora1) mRNA and protein expressions were significantly down‐regulated in the heart of zfp91‐deletion mice with TAC. Zfp91 overexpression reversed isoproterenol‐induced cardiomyocyte hypertrophy, which was abolished by selective Adora1 antagonist. Dual‐luciferase reporter and ChIP‐qPCR assays indicated that zfp91 acted on Adora1 promoter through its binding site. Last, Adora1 agonist rescued heart dysfunction and cardiac hypertrophy in zfp91 loss mice after TAC. Zfp91 may transcriptionally regulate Adora1 expression in the heart, which mainly maintained cardiac homeostasis under pressure overload status. It will provide a new approach to treat cardiac hypertrophy.