Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 (infancy), 59,257,530 (adolescence) and 72,729,636 (adulthood) reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of reg-ulatory genes up-regulated and some crucial pathways activated. Transcription factor (TF) analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regula-tion. Moreover, our data revealed a drastic increase in myelin basic protein (MBP)-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since mouse adolescence. In addition, differential gene expression analysis indicated the activation of rhythmic pathway, suggesting the function of rhythmic movement since adolescence;Furthermore, during infancy and adolescence periods, gene expression related to axon repulsion and attraction showed the opposite trends, indicating that axon repulsion was activated after birth, while axon attraction might be activated at the embryonic stage and declined during the postnatal develop-ment. Our results from the present study may shed light on the molecular mechanism underlying the postnatal development of the mammalian cerebrum.

Our recent investigation in the protist Trichomonas vaginalis suggested a DNA sequence periodicity with a unit length of 120.9 nt, which represents a sequence signature for nucleosome positioning. We now extended our observation in higher eukaryotes and identified a similar periodicity of 175 nt in length in Caenorhabditis elegans. In the process of defining the sequence compositional characteristics, we found that the 10.5-nt periodicity, the sequence signature of DNA double helix, may not be sufficient for cross-nucleosome positioning but provides essential guiding rails to facilitate positioning. We further dissected nucleosome-protected sequences and identified a strong positive purine (AG) gradient from the 5'-end to the 3'-end, and also learnt that the nucleosome-enriched regions are GC-rich as compared to the nucleosome-free sequences as purine content is positively correlated with GC content. Sequence characterization allowed us to develop a hidden Markov model (HMM) algorithm for decoding nucleosome positioning computationally, and based on a set of training data from the fifth chromosome of C. Elegans, our algorithm predicted 60%-70% of the well-positioned nucleosomes, which is 15%-20% higher than random positioning. We concluded that nucleosomes are not randomly positioned on DNA sequences and yet bind to different genome regions with variable stability, well-positioned nucleosomes leave sequence signatures on DNA, and statistical positioning of nucleosomes across genome can be decoded computationally based on these sequence signatures.

Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation.However,when investigating the H3K4me3 profiles in the mouse cerebrum and testis,we discovered that H3K4me3 also has a significant enrichment at the 3' end of actively transcribed (sense) genes,named as 3′-H3K4me3.3′-H3K4me3 is associated with ～15％ of protein-coding genes in both tissues.In addition,we examined the transcriptional initiation signals including RNA polymerase II (RNAPII)binding sites and 5′-CAGE-tag that marks transcriptional start sites.Interestingly,we found that 3′-H3K4me3 is associated with the initiation of antisense transcription.Furthermore,3′-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes,implying that 3′-H3K4me3 is involved in the activation of antisense transcription.Taken together,our findings suggest that H3K4me3 may be involved in the regulation of antisense transcription that initiates from the 3′ end of sense genes.In addition,a positive correlation was also observed between the expression of antisense and the associated sense genes with 3'-H3K4me3 modification.More importantly,we observed the 3'-H3K4me3 enrichment among genes in human,fruitfly and Arabidopsis,and found that the sequences of 3'-H3K4me3-marked regions are highly conserved and essentially indistinguishable from known promoters in vertebrate.Therefore,we speculate that these 3'-H3K4me3-marked regions may serve as potential promoters for antisense transcription and 3′-H3K4me3 appear to be a universal epigenetic feature in eukaryotes.Our results provide a novel insight into the epigenetic roles of H3K4me3 and the regulatory mechanism of antisense transcription.

The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years,but most of these studies were performed in mammalian cell lines.In this work,wegenerated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChlP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology.We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression,function and development.Moreover,we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes,which contradicts the findings in previous studies.Finally,we observed that bivalent domains,with both H3K4me3 and H3K27me3,existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes.However,the bivalent domains tend towards a "winner-takes-all" approach to regulate the expression of associated genes.We also verified the above results in mouse ES cells.As expected,the results in ES cells are consistent with those in cerebrum and testis.In conclusion,we present two very important findings.One is that H3K4me3 and H3K27me3 rarely occur in silent genes.The other is that bivalent domains may adopt a "winner-takes-all" principle to regulate gene expression.

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.