Genetic spectrum of MCM3AP and its relationship with phenotype of Charcot-Marie-Tooth disease.

Mutations in MCM3AP have recently been reported to cause autosomal recessive Charcot-Marie-Tooth disease (CMT). However, only nine CMT families with MCM3AP mutations have been reported and genotype-phenotype correlation remains unclear. This study aimed to investigate the genetic spectrum of MCM3AP and its relationship with phenotype of CMT. Whole-exome sequencing (WES) was performed in the family and variants were validated by Sanger sequencing. Reverse transcription-PCR (RT-PCR) were performed in splicing analysis. We reported a novel splicing variant (c.5634-1G>T) and a known missense variant (c.2633G>A, p.Arg878His). Functional studies showed that c.5634-1G>T led to splicing defect and aberrant transcript eliminated by nonsense-mediated mRNA decay. The symptom of the patient was less severe and slowly progressed with axonal peripheral neuropathy compared to the reported CMT patients. Genotype-phenotype correlation analysis indicated that affected individuals with null mutations presented with delayed independent walking. The percentage of intellectual disability and loss of ambulation in the null group tended to be greater, although this failed to reach statistical significance. Our findings expand the genetic spectrum of MCM3AP and suggest that genotype-phenotype correlation would help genetic counseling of MCM3AP in CMT patients.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

Endogenous biopolymer hydrolysis for enhancing short-chain fatty acids recovery from excess sludge: Combination of lysozyme-catalyzing and cation exchange resin-mediated metal regulation.

In decades, anaerobic fermentation with short-chain fatty acids (SCFAs) recovery from excess sludge have attained rising attention. However, rigid particulate organic matter (POMs) structure with slow hydrolysis limited anaerobic fermentation performance of excess sludge. Remarkable sludge hydrolysis performance was supposed to be achievable by the synchronous EPS repture and microbial cell lysis. This study clarified the improvement of overall anaerobic fermentation performance by combination treatment of lysozyme (Lyso) catalysis and metal regulation (MR). The Lyso + MR treatment triggered EPS rupture by protein structure deflocculation while catalyzing microbial cell lysis, which promoted massive extracellular and intracellular POMs hydrolysis. As a result, a significant amount of SCOD (5646.67 mg/L) was produced. Such endogenous organic matters hydrolysis led to considerable SCFAs accumulation (3651.14 mg COD/L) through 48-h anaerobic fermentation at 1.75 g/g SS cation-exchange resin and Lyso dosage of 10% (w/w), which was 5.945 times higher than that in the control. Additionally, it suggested that most of the recovered SCFAs remained in fermentative liquid after chemical conditioning and mechanical dewatering towards solid-liquid separation, which provided considerable economic benefit of 363.6-1059.1 CNY/ton SS.

Sulfur rich microporous polymer enables rapid and efficient removal of mercury(II) from water.

Design and synthesis of adsorbents for efficient decontamination of hazardous contaminants Hg2+ from wastewater, based on a facile and economical strategy, is an attractive target. Here, a novel sulfur rich microporous polymer (sulfur content of 31.4 wt %) with high surface area as well as densely populated sulfur atom with fast accessibility was reported to remove mercury (II) from water. The as prepared polymer (SMP) exhibited high binding affinity, high adsorption capacities, rapid adsorption kinetics, and good recyclability for Hg2+. The adsorption capacity of SMP was 595.2 mg g-1. Furthermore, SMP could reduce trace concentrations of Hg2+ from 200 p. p. b. to a level below drinking water standards (2 p. p. b.) within 3 min. This work allows large-scale production of sulfur rich porous materials for the practical application in water treatment.

Temporal and spatial expression of osteoprotegerin and receptor activator of nuclear factor -kappaB ligand during mandibular distraction in rats.

PURPOSE: The expression profiles of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) were investigated in the distraction region to reveal bone remodelling characters during mandibular distraction osteogenesis. MATERIAL AND METHODS: Osteotomies were performed and external distractors were used on the mandibles of 42 adult male SD rats. After a 5-day latency period, the distractors were activated at a rate of 0.4mm/day for 6 days, followed by a 4-week consolidation period. Radiographs were taken, and specimens were harvested at the end of the latency period, when distraction was completed, and at the end of 1, 2, 3 and 4 weeks of the consolidation period. Tartrate-resistant acid phosphatase staining was used to detect activated osteoclasts. Temporospatial expression of osteoprotegerin and RANKL was investigated by using immunohistochemistry, in situ hybridization and reverse transcription polymerase chain reaction. Semi-quantitative analysis was used to characterize osteoprotegerin (OPG). RANKL and RANKL/OPG ratio. RESULTS: In all time points, osteoprotegerin and RANKL were co-localized in bone marrow lining cells, osteoblasts and newly embedded osteocytes. Osteoprotegerin mRNA expression increased to a peak when distraction was completed and maintained this level until the end of week 2 of the consolidation period. RANKL mRNA expression increased steadily until the end of week 1 of the consolidation period and maintained a peak level until the end of week 3, with a slight decrease at the end of week 2. The RANKL/OPG ratio increased continuously and reached its highest level at the end of weeks 3 and 4 of the consolidation period. Tartrate-resistant acid phosphatase staining positive osteoclasts were mainly detected at weeks 2, 3 and 4 of the consolidation period in bone marrow cavities and bone surfaces. CONCLUSIONS: The temporospatial expression patterns of osteoprotegerin and RANKL suggest that the osteoblast lineage cell network orchestrates bone remodelling during distraction osteogenesis and most activated bone resorption takes place during weeks 3 and 4 of the consolidation phase.

Efficient fixation of CO2 by a zinc-coordinated conjugated microporous polymer.

Zinc-coordinated conjugated microporous polymers (Zn-CMPs), prepared by linking salen zinc and 1,3,5-triethynylbenzene, exhibit extraordinary activities (turnover frequencies of up to 11600 h(-1) ), broad substrate scope, and group tolerance for the synthesis of functional organic carbonates by coupling epoxides with CO2 at 120 °C and 3.0 MPa without the use of additional solvents. The catalytic activity of Zn-CMP is comparable to those of homogeneous catalysts and superior to those of other heterogeneous catalysts. This catalyst could be reused more than ten times without a significant decrease in performance.

[Molecular mechanism of bone remodelling during mandibular distraction osteogenesis in rats].

OBJECTIVE: To study the expression profiles of osteoprotegerin (OPG) and receptor activator of nuclear factor-KB ligand (RANKL) in the distraction region and to investigate the mechanism of bone remodelling during mandibular distraction osteogenesis. METHODS: Osteotomies were performed and external distractors were installed on the mandibles of 42 adult male SD rats. After a 5-day latency period, the distractors were activated at a rate of 0.4 mm/day for 6 days, followed by a 4-week consolidation period. Radiographs were taken, and specimens were harvested at the end of the latency period, when distraction was completed, and at of 1, 2, 3 and 4 weeks of the consolidation period. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the activated osteoclasts. Temporospatial expression of OPG and RANKL was investigated by using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Semi-quantitative analysis was used to characterize OPG,RANKL and RANK/OPG ratio. RESULTS: In all time points, OPG and RANKL were co-localized in bone marrow lining cells, osteoblasts and newly embedded osteocytes. OPG mRNA expression increased to a peak level when distraction was completed and maintained the level until the end of 2nd week of the consolidation period. RANKL mRNA expression increased steadily until the end of 1 st week of the consolidation period and maintained a peak level until the end of 3rd week, with a slight decrease at the end of 2nd week. The RANKL/OPG ratio increased continuously and reached its highest level at the end of 3rd and 4th week of the consolidation period. TRAP positive osteoclasts were mainly detected at 2, 3 and 4 weeks of the consolidation period in bone marrow cavities and bone surfaces. CONCLUSIONS: The temporospatial expression patterns of osteoprotegerin and RANKL suggest that osteoblasts and the lineage cell network orchestrates bone remodelling during distraction. Osteogenesis and the most activated bone resorption takes place during 3rd and 4th week of the consolidation phase.

Fluorinated imidazoles as proton carriers for water-free fuel cell membranes.

We propose an alternative new material (2,4,5-trifluoroimidazole impregnated Nafion) for use as a high-temperature, water-free membrane for proton-exchange membrane fuel cells. This material has been tested computationally using molecular dynamics and quantum mechanics techniques, leading to an estimated conductivity of approximately 0.06 S/cm at 177 degrees C. This material overcomes the weakness of the imidazole-impregnated membranes, i.e., the poisoning of the Pt electrode. We find that 2,4,5-trifluoroimidazole binds weakly to platinum surfaces, so poisoning is not expected.

[Non-osteogenic malocclusion after anatomic reduction and miniplate rigid fixation in condylar neck and subcondylar fractures].

OBJECTIVE: To analysis the cause of malocclusion that was found in patients suffering from condylar neck and subcondylar fractures after perfectly anatomic reduction and rigid fixation. METHODS: There were 23 cases of malocclusion in the patients of condylar neck and subcondylar fractures after anatomic reduction and rigid fixation during 1994 to 2001. The possible reasons were studied, and the treatment methods were proposed. RESULTS: Both distortion and(or) fracture of miniplates and displacement anain of the condylar process after operation were not found in all 23 cases. There were 6 cases of open bite at the molar teeth of the fractured side, while the normal occlusions were showed in the nonfractured side. 11 cases showed that the whole mandibles were moved slightly to the nonfractured side. 4 cases showed that the mandible of fractured side moved slightly to the nonfractured side and the occlusion of nonfractured side were normal. 2 cases showed premature contact at the fractured molar teeth and the anterior teeth showed open bite. There were 5 cases of facial nerve damages, 2 cases wound infection, 2 cases TMJ chronic pain and 1 cases TMJ click and(or) murmur. CONCLUSIONS: Although the anatomical reduction and miniplate rigid fixation were operated on the condylar neck and subcondylar fractures, there were probably having the chance of showing malocclusion. The malocclusion was not caused by the fracture itself, but in the TMJ and/or muscular injury. Therefore, the malocclusion can be cured with intermaxillary elastic traction and functional exercise. Sometimes, the occlusal adjustment may be performed to resume the normal occlusion. In any case, operation is not needed.