Modulating the Acidic and Basic Site Concentration of Metal-Organic Framework Derivatives to Promote the Carbon Dioxide Epoxidation Reaction.

Metal-organic framework (MOF) is an ideal precursor/template for porous carbon, and its active components are uniformly doped, which can be used in energy storage and catalytic conversion fields. Metal-organic framework PCN-224 with carboxylporphyrin as the ligand was synthesized, and then Zn2+ and Co2+ ions were coordinated in the center of the porphyrin ring by post-modification. Here, PCN-224-ZnCo with different ratios of bimetallic Zn2+ /Co2+ ions were used as the precursor, and the metal-nitrogen-carbon(M-N-C) material of PCN-224-ZnCo-950 was obtained by pyrolyzing the precursor at 950 °C in Ar. Because Zn is easy to volatilize at 950 °C, the formed M-N-C materials can reflect different Co contents and different basic site concentrations. The formed material still maintains the original basic framework. With the increase of Zn2+ /Co2+ ratio in precursor, the concentration of N-containing alkaline sites in pyrolysis products gradually increase. Compared with the precursor, PCN-224-ZnCo1 -950 with Zn2+ /Co2+ =1 : 1 has greatly improved basicity and suitable acidic/ alkaline site concentration. It can be efficiently used to carbon dioxide absorption and catalyze the cycloaddition of CO2 with epoxide. More importantly, the current method of adjusting the acidic/basic sites in M-N-C materials through volatilization of volatile metals can provide an effective strategy for adjusting the catalysis of MOF derivatives with porphyrin structure.

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.

OBJECTIVE: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population. METHODS: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing. RESULTS: Clinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively. SIGNIFICANCE: This is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.

Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease.

PURPOSE: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive hypomyelination disorder characterized by nystagmus, ataxia, impaired motor development, and progressive spasticity. Identification of proteolipid protein 1 (PLP1) mutations in Chinese patients with Pelizaeus-Merzbacher disease (PMD) and confirmation of the biological impacts of the identified mutations are the aims of this study. METHODS: An analysis of clinical materials and a follow-up study were conducted for the patients with PMD. Sequencing and immunofluorescence were applied for molecular analysis of the causative gene PLP1. RESULTS: We identified PLP1 mutations in seven male patients with PMD. Three novel missense mutations (c.353C>G, p.T118R; c.623G>T, p.G208V; c.709T>G, p.F237V) and three reported missense mutations (c.467C>T, p.T156I; c.517C>T, p.P173S; c.646C>T, p.P216S) of PLP1 were identified from seven Chinese PMD patients. The three mutations (F237V in patient 2, P216S in patient 5 and T156I in patient 6) were de novo. Mutant proteins were trapped in the lumen of endoplasmic reticulum. CONCLUSION: We have identified six pathogenic mutations, enriching the specific spectrum of missense mutations in the patients with PMD. The six PLP1 mutations are probably pathogenic. By reviewing the known PLP1 mutations, we have preliminarily revealed the position of missense mutation may be associated with the severity of PMD.

Redefining the modular organization of the core Mediator complex.

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.

Structural flexibility and functional interaction of Mediator Cdk8 module.

Mediator is a highly conserved large protein complex (25 proteins, >1000 kDa) and preeminently responsible for eukaryotic transcription, which contains a dissociable 'Cdk8 module'. Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation, the detailed structure, and subunit organization, molecular mechanism how it regulates transcription remain elusive. Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural flexibility. The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo. An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro, which is presumed to be an active functional state of Mediator. Taken together, our results illuminated the detailed architecture of Cdk8 module, and suggested the Cdk8 module could positively regulate transcription by modulating Mediator conformation.

[Relationship between gender, experience of migration and premarital sex among out-of-school youths in rural Hainan, China].

OBJECTIVE: To assess pre-marital sex behavior and its relationship with gender and experience of migration among 16 - 24 years-old out-of-school youths in rural Hainan province, China. METHODS: 160 eligible youths from each of the 2 townships in County A and 80 from each of the 6 townships in County B were recruited, under equal proportion on gender, age distribution and experience of migration. An interviewer-administered, standardized questionnaire was used. RESULTS: 760 eligible participants (with each gender of 380) were interviewed. There were no significant differences in the proportions of reporting as sexually active (56.8% and 57.9%) or having premarital sex (54.5% and 50.0%) between male and female youths. However, among those sexually active participants, the average age at first sexual intercourse was (18.2 ± 1.9 years or 19.2 ± 1.8 years, P < 0.01), the average age of first-time leaving hometown for work (18.0 ± 2.3 years or 16.5 ± 1.9 years P < 0.01) and the percentage of having first sexual intercourse before 18 years old (59.3% vs. 35.5%, P < 0.01) were different between males and females. 31.2% of the male youths reported that their sexual debut happened before they left their hometown for work and 45.9% of the sex debut appeared within 1 year after they left hometown. However, 78.5% of the sexually active female youths reported their sexual debut happened 1 year after leaving their hometown. Data from the multivariate analysis showed that being away from hometown for more than 3 months and having more friends who presumably had presumably pre-marital sex experiences were more likely to report pre-marital sex behavior. Older men were more likely to report pre-marital sex behavior than the younger ones. Married women were more likely to report pre-marital sex behavior than the unmarried ones. Through multivariate analysis on unmarried men, data showed that those having had experience on migration and at older age were associated with experiencing premarital sex. CONCLUSION: Gender difference was identified on the pattern of migration and its relationship with premarital sex among out-of-school rural youths in Hainan province. When prevention program is developed for rural youth, these differences should be taken into account.