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Background Acute meningitis and encephalitis syndromes (AMES) is a severe neurological infection which causes high case fatality and severe sequelae in children. To determine the etiology of childhood AMES in Shenzhen, a hospital-based study was undertaken. Methods A total of 240 cerebrospinal fluid (CSF) samples from 171 children meeting the case definition were included and screened for 12 common causative organisms. The clinical data and conventional testing results were collected and analyzed. Whole genome sequencing was performed on a Neisseria meningitidis isolate. Results A pathogen was found in 85 (49.7%) cases; Group B Streptococcus (GBS) was detected in 17 cases, Escherichia coli in 15, Streptococcus pneumoniae in 14, enterovirus (EV) in 13, herpes simplex virus (HSV) in 3, N. meningitidis in 1, Haemophilus influenzae in 1, and others in 23. Notably, HSV was found after 43 days of treatment. Twelve GBS and 6 E. coli meningitis were found in neonates aged less than 1 month; 13 pneumococcal meningitis in children aged > 3 months; and 12 EV infections in children aged > 1 year old. The multilocus sequence typing of serogroup B N. meningitidis isolate was ST-3200/CC4821. High resistance rate to tetracycline (75%), penicillin (75%), and trimethoprim/sulfamethoxazole (75%) was found in 4 of S. pneumoniae isolates; clindamycin (100%) and tetracycline (100%) in 9 of GBS; and ampicillin (75%) and trimethoprim/sulfamethoxazole (67%) in 12 of E. coli . Conclusions The prevalence of N. meningitidis and JEV was very low and the cases of childhood AMES were mainly caused by other pathogens. GBS and E. coli were the main causative organisms in neonates, while S. pneumoniae and EV were mainly found in older children. HSV could be persistently found in the CSF samples despite of the treatment. A better prevention strategy for GBS, the introduction of pneumococcal vaccine, and incorporation of PCR methods were recommended.

Emerging evidence suggests that microRNAs (miRNAs) are essential for metabolic haemostasis of liver tissues. Among them, miR‐33a is supposed to modulate the cholesterol export and fatty acid oxidation, but whether miR‐33a involves in the process of fatty liver disease is unclear. To disclose the hypothesis, we utilized miR‐33a mimic and antisense to explore their effects in primary hepatocytes or high‐fat diet (HFD)‐fed mice. Treatment with palmitic acid (PA) or HFD significantly increased the expression of miR‐33a in hepatocytes or liver tissues. In primary hepatocytes, miR‐33a mimic decreased mitochondrial function, including reduction of ATP production and oxygen consumption, whereas miR‐33a inhibition protected PA‐induced mitochondrial dysfunction. Interestingly, miR‐33a selectively suppressed mitochondrial complex I activity and protein expression, but not other complexes. Through bioinformatics prediction, we found miR‐33a directly targeted on the 3′‐UTR of NDUFA5. Dual‐luciferase reporter analysis further confirmed the direct suppression of miR‐33a on NDUFA5 expression. More importantly, administration of miR‐33a antisense could effectively restore HFD‐induced mitochondrial dysfunction through up‐regulation of NDUFA5 levels. Mice treated with miR‐33a antisense also exhibited improved liver function and structural disorders under obese status. Taken together, miR‐33a was an important mediator of hepatocyte mitochondrial function, and the therapeutic benefits implied miR‐33a antisense had the potential clinical application in combating the fatty liver disease.

Fragile X mental retardation protein (FMRP), associated with fragile X syndrome, is known as an RNA-binding protein to regulate gene expression at post-transcriptional level in the brain. FMRP is also involved in microRNA (miRNA) biogenesis during the process of precursor miRNA (pre-miRNA) into mature miRNA. However, there is no description of the effect of FMRP on primary miRNA (pri-miRNA) processing. Here, we uncover a novel role of FMRP in pri-miRNA processing via controlling Drosha translation. We show that the expression of DROSHA protein, instead of its messenger RNA (mRNA) transcripts, is downregulated in both the hippocampus of Fmr1-knockout mice and the FMRP-knockdown Neuro-2a cells. Overexpression or knockdown FMRP does not alter Drosha mRNA stability. Immunoprecipitation and polysome analyses demonstrate that FMRP binds to the Drosha mRNA and enhances its translation. Additionally, we show that loss of FMRP in Fmr1-deficient mice results in the accumulation of three in six analyzed pri-miRNAs and the reduction of the corresponding pre-miRNAs and mature miRNAs. Thus, our data suggest that FMRP is involved in pri-miRNA processing via enhancing DROSHA expression that may play an important role in fragile X syndrome.

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