Human Dicer (hDicer) is a multi-domain protein belonging to the RNase III family. It plays pivotal roles in small RNA biogenesis during the RNA interference (RNAi) pathway by processing a diverse range of double-stranded RNA (dsRNA) precursors to generate ∼22 nt microRNA (miRNA) or small interfering RNA (siRNA) products for sequence-directed gene silencing. In this work, we solved the cryoelectron microscopy (cryo-EM) structure of hDicer in complex with its cofactor protein TRBP and revealed the precise spatial arrangement of hDicer's multiple domains. We further solved structures of the hDicer-TRBP complex bound with pre-let-7 RNA in two distinct conformations. In combination with biochemical analysis, these structures reveal a property of the hDicer-TRBP complex to promote the stability of pre-miRNA's stem duplex in a pre-dicing state. These results provide insights into the mechanism of RNA processing by hDicer and illustrate the regulatory role of hDicer's N-terminal helicase domain.

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The need to implement wastewater reuse in Beijing is discussed. Based on the investigation of the built wastewater reuse projects in Beijing, the differences between small wastewater reuse system and large systems were analyzed according to the technical, economical and social issues. The advantages and disadvantages of the small system and the large system were then given. In wastewater reuse planning in Beijing urban region, the large system was adopted. The rations of reclaimed water for difference land use type, including industrial reuse, municipal reuse, grass irrigation, and scenes water reuse were determined. Then according to the land use information in every block in central Beijing, using GIS techniques, the amounts of the reclaimed water needed in every block were calculated, and the main pipe system of reclaimed water was planned.

Although more than 80 psoriasis genetic risk loci have been reported through genome-wide association studies (GWASs), the genetic mechanism of psoriasis remains unclear. To identify novel candidate genes associated with psoriasis and reveal the potential effects of genetic factors in the development of psoriasis, we conducted a transcriptome-wide association study (TWAS) based on summary statistics from GWAS of psoriasis (5175 cases and 447 089 controls) and gene expression levels from six tissues datasets (blood and skin). We identified 11 conditionally independent genes for psoriasis after Bonferroni corrections, such as the most significant genes UBLCP1 (PYFS = 2.98 × 10−16), and LCE3C (PSNSE = 9.72 × 10−12, PSSE = 6.24 × 10−12). The omnibus test identified additional 5 genes associated with psoriasis via the joint association model from multiple reference tissues. Among the 16 identified genes, 5 genes (CTSW, E1F1AD, KLRC3, FIBP, and EFEMP2) were regarded as novel genes for psoriasis. We evaluated the 16 candidate genes by querying public databases and identified 11 differentially expressed genes and 8 genes proved by the knockout mice models. Through GO enrichment analyses, we found that TWAS genes were enriched in the known GO terms associated with skin development, such as cornified envelope (P = 4.80 × 10−8) and peptide cross-linking (P = 1.50 × 10−7). Taken together, our results detected multiple novel candidate genes for psoriasis, providing clues for understanding the genetic mechanism of psoriasis.