Clinical report and genetic analysis of a novel variant in ZMIZ1 causing neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies in a Chinese family

He Liting,Wang Yao,Pan Jiahua,Guo Limin,Zhou Haoquan,Zhang Lan 한국유전학회 2024 Genes & Genomics Vol.46 No.4

Background Neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies (NEDDFSA) is a rare and phenotypically variable disorder. The zinc finger MIZ-type containing 1 gene (ZMIZ1) is a causative gene of NEDDFSA that encodes a protein inhibitor of the activated STAT-like family transcriptional regulator. Given the rarity of reported NEDDFSA cases, new phenotypes and genotypes of this disorder are still being discovered. Objective This study describes the phenotype characteristics of a Chinese NEDDFSA family caused by a novel ZMIZ1 variant. Methods We reviewed the clinical phenotype of a Chinese patient with NEDDFSA and performed whole-exome sequencing (WES) of the patient’s family. We simulated the potential biological harmfulness of the mutant protein. Plasmids were constructed and used for western blot and immunofluorescence assays to analyze protein expression levels. Results The patient was a 6-month-old male infant who exhibited dysmorphic facial features, neurodevelopmental abnormalities, congenital heart disease, and previously unreported genitourinary system anomalies. WES revealed a non-frameshift deletion variant in ZMIZ1 (NM_020338.4: c.858_875del, p.Val288_Ala293del), resulting in a structural alteration in the protein’s alanine-rich domain. Western blot and immunofluorescence assays indicated a significant decrease in the expression level of the mutant ZMIZ1 protein compared to the wild-type protein. Conclusion The clinical manifestations of this patient may be associated with the ZMIZ1 variant, and the structural alteration in the alanine-rich domain of the ZMIZ1 protein may contribute to a more complex disease phenotype. These results expand the genotype–phenotype correlation of ZMIZ1. Background Neurodevelopmental disorder with dysmorphic factors and distal skeletal anomalies (NEDDFSA) is a rare and phenotypically variable disorder. The zinc finger MIZ-type containing 1 gene (ZMIZ1) is a causative gene of NEDDFSA that encodes a protein inhibitor of the activated STAT-like family transcriptional regulator. Given the rarity of reported NEDDFSA cases, new phenotypes and genotypes of this disorder are still being discovered. Objective This study describes the phenotype characteristics of a Chinese NEDDFSA family caused by a novel ZMIZ1 variant. Methods We reviewed the clinical phenotype of a Chinese patient with NEDDFSA and performed whole-exome sequencing (WES) of the patient’s family. We simulated the potential biological harmfulness of the mutant protein. Plasmids were constructed and used for western blot and immunofluorescence assays to analyze protein expression levels. Results The patient was a 6-month-old male infant who exhibited dysmorphic facial features, neurodevelopmental abnormalities, congenital heart disease, and previously unreported genitourinary system anomalies. WES revealed a non-frameshift deletion variant in ZMIZ1 (NM_020338.4: c.858_875del, p.Val288_Ala293del), resulting in a structural alteration in the protein’s alanine-rich domain. Western blot and immunofluorescence assays indicated a significant decrease in the expression level of the mutant ZMIZ1 protein compared to the wild-type protein. Conclusion The clinical manifestations of this patient may be associated with the ZMIZ1 variant, and the structural alteration in the alanine-rich domain of the ZMIZ1 protein may contribute to a more complex disease phenotype. These results expand the genotype–phenotype correlation of ZMIZ1.

siRNA-Mediated Suppression of Synuclein γ Inhibits MDA-MB-231 Cell Migration and Proliferation by Downregulating the Phosphorylation of AKT and ERK

Jingsong He,Ni Xie,Jianbo Yang,Hong Guan,Weicai Chen,Huisheng Wu,Zishan Yuan,Kun Wang,Guojin Li,Jie Sun,Limin Yu 한국유방암학회 2014 Journal of breast cancer Vol.17 No.3

Purpose: Synuclein-γ (SNCG), which was initially identified asbreast cancer specific gene 1, is highly expressed in advancedbreast cancers, but not in normal or benign breast tissue. Thisstudy aimed to evaluate the effects of SNCG siRNA-treatmenton breast cancer cells and elucidate the associated mechanisms. Methods: Vectors containing SNCG and negative control(NC) siRNAs were transfected into MDA-MB-231 cells; mRNAlevels were determined by real-time polymerase chain reaction. Cell proliferation was evaluated using the MTT assay, cell migrationwas assessed by the Transwell assay, apoptosis and cellcycle analyses were conducted with the flow cytometer, andWestern blot analysis was performed to determine the relativelevels of AKT, ERK, p-AKT, and p-ERK expression. Results:SNCG mRNA levels were significantly reduced in MDA-MB-231cells transfected with SNCG siRNA. Our results indicate that inSNCG siRNA-treated cells, cell migration and proliferation decreasedsignificantly, apoptosis was induced, and the cell cyclewas arrested. Western blot analysis indicated that the proteinlevels of p-AKT and p-ERK were much lower in the SNCG siRNA-treated groups, than in the control and NC groups. Conclusion:SNCG siRNA could decrease the migration and proliferationof breast cancer cells by downregulating the phosphorylationof AKT and ERK.

Enhancement of Kidney Invigorating Function in Mouse Model by Cistanches Herba Dried Rapidly at a Medium High Temperature

Yehong Guo,Limin Wang,Qian Li,Cheng Zhao,Ping He,Xudong Ma 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.12

Cistanches Herba is a popular Traditional Chinese Medicine and functional food that is used to treat kidney yang deficiency (KYD) in China. In this study, we investigated the effects of different drying methods for Cistanches Herba on kidney invigoration and yang strengthening. We established a mouse model of KYD by intraperitoneal injection of hydrocortisone for 8 days. We dried slices of Cistanches Herba in the sun, in the shade, in a microwave, or in an oven at 40°C, 60°C, 80°C or 100°C, then prepared and administered extracts to the mice by gastric gavage. We measured and evaluated the echinacoside (ECH) and acteoside (ACT) contents of the extracts, as well as the mice's body weight; testicular, epididymal, hepatic, and renal coefficients; and semen quality. All the Cistanches Herba extracts, obtained using different drying techniques, improved symptoms of KYD diagnosis in mice. Among them, treatments with Cistanches Herba dried in a microwave and dried in an oven at 100°C had the best therapeutic effects. Our results suggested that the higher the total content of ECH and ACT in Cistanches Herba extracts, the better the effects of kidney invigoration and yang strengthening. In addition, shorter drying times at higher temperatures lead to the highest recoveries of active components, and Cistanche dried in the sun at a medium-high temperature can improve sperm quality in mice.

A review of the recent advances in design of corrugated plate packs applied for oil–water separation

Yunrui Han,Limin He,Xiaoming Luo,Yuling Lü,Kaiyue Shi,Jianheng Chen,Xin Huang 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.53 No.-

The paper reviews the contradictions and problems existing on the oil–water separation technology in detail from the perspective of experiments, numerical simulation and coalescence mechanism analysis, and the future research directions are forecasted. The review points out that the law of droplet coalescence on the corrugated plates can be studied from the perspective of microscopic experiment and mechanism research, which are the theoretical bases for clarifying the coalescence mechanism of the corrugated plates and refining the droplet coalescence mathematical model. The further research topics are also clarified to promote future applications by combining the coalescence technology with surface bionic technology.

Effects of sweetener sucralose on diet preference, growth performance and hematological and biochemical parameters of weaned piglets

Zhang, Wenwei,He, Holden,Gong, Limin,Lai, Wenqing,Dong, Bing,Zhang, Liying Asian Australasian Association of Animal Productio 2020 Animal Bioscience Vol.33 No.5

Objective: Two experiments were conducted to investigate the effects of dietary sucralose on diet preference and growth performance of weaned piglets, and a third experiment was a 28-d safety study to examine if high-dose sucralose could affect the health state of weaned piglets. Methods: In experiment one, 48 piglets had free access to a corn-soybean based diet and the same diet supplemented with 150 mg/kg sucralose for 15 d. In experiment two, 180 piglets were blocked into 5 treatments with 6 replications. They were fed basal diets supplemented with 0, 75, 150, 225, and 300 mg/kg sucralose for 28 days. In experiment three, 108 piglets were randomly assigned to 3 treatments and fed diets supplemented with 0, 150 (suitable level), and 1,500 (ten-fold suitable level) mg/kg sucralose for 28 d. Results: The experiment 1 showed that piglets preferred (p<0.05) diets containing sucralose during experimental period. In experiment 2, piglets fed a diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than pigs in the control group and other treatment groups during the experiment period. The concentrations of sucralose over 150 mg/kg may decrease feed intake. However, no difference in feed conversion ratio was observed. In experiment 3, piglets fed diet supplemented with 150 mg/kg sucralose had a higher ADG and ADFI than that of pigs in the control group and 1,500 mg/kg treatment groups during the experiment period. Clinical blood metabolites, organ index and histological morphology were not significantly different between sucralose treatments. Conclusion: Sucralose can promote feed intake and thereby improve growth performance of weaned piglets. Moreover, inclusion of 1,500 mg/kg sucralose was demonstrated to have no observed adverse effects. Supplementing 150 mg/kg sucralose for weaned piglets is recommended in this study.

Dynamic optimization design of the suspension parameters of car bodymounted equipment via analytical target cascading

Jie Chen,Yangjun Wu,Limin Zhang,Xiaolong He,Shijie Dong 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.5

Under dynamic conditions, the dynamic force between the suspended equipment and the car body is substantially increased. This increase not only affects the ride comfort but also substantially raises the likelihood of fatigue damage to the suspended equipment. A multiobjective analytical target cascading (ATC) optimization is proposed to improve the ride comfort of high-speed trains and reduce the vibration of the suspended equipment. A mathematical simulation model of the vehicle equipment system is established, and the acceleration frequency-response function expression of the car body and the suspension system is obtained. The comfort index of the car body and the acceleration root mean square (RMS) of the suspended equipment are calculated by combining the German vertical irregular track spectrum and the comfort filter function. Meanwhile, the ATC method is used to optimize the car body comfort index and the acceleration RMS of the underframe suspended equipment. Then, the availability of the optimization method is evaluated via numerical simulation. Compared with the original suspension scheme of the underframe equipment, when the running speed of the vehicle is 300 km/h, the RMS value of the vibrational acceleration of the underframe equipment after optimization decreases by 19.9 %, and the ride comfort indexes at the car body center and above the front and rear bogies are improved by 6.4 %, 0.1 %, and 1.1 %, respectively. Simulation results demonstrate that ATC optimization can improve the railway vehicle ride comfort and reduce the vibration of the suspended equipment. This paper provides a new approach to the suspension parameter design of equipment.

Risk Factors for Poor Outcomes Following Minimally Invasive Discectomy: A Post Hoc Subgroup Analysis of 2-Year Follow-up Prospective Data

Zihao Chen,Lei He,Lijun Huang,Zhongyu Liu,Jianwen Dong,Bin Liu,Ruiqiang Chen,Liangming Zhang,Peigen Xie,Limin Rong 대한척추신경외과학회 2022 Neurospine Vol.19 No.1

Objective: A post hoc subgroup analysis of prospectively collected data from a randomized controlled trial was conducted to identify risk factors related to poor outcomes in patients who underwent minimally invasive discectomy. Methods: Patients were divided into satisfied and dissatisfied subgroups based on Oswestry Disability Index (ODI), visual analogue scale (VAS) back pain score (VAS-back) and leg pain score (VAS-leg) at short-term and midterm follow-up according to the patient acceptable symptom state threshold. Demographic characteristics, radiographic parameters, and clinical outcomes between the satisfied and dissatisfied subgroups were compared using univariate and multivariate analysis. Results: A total of 222 patients (92.1%) completed 2-year follow-up, and the postoperative ODI, VAS-back, and VAS-leg were significantly improved after surgery as compared to preoperatively. Multivariate analysis indicated older age (p = 0.026), lateral recess stenosis (p = 0.046), and lower baseline ODI (p = 0.027) were related to poor short-term functional improvement. Higher baseline VAS-back (p = 0.048) was associated with poor short-term relief of back pain, while absence of decreased sensation (p = 0.019) and far-lateral disc herniation (p = 0.004) were associated with poorer short-term relief of leg pain. Lumbar facet joint osteoarthritis was identified as a risk factor for poor functional improvement (p = 0.003) and relief of back pain (p = 0.031). Disc protrusion (p = 0.036) predicted poorer relief of back pain at midterm follow-up. Conclusion: In this study, several factors were identified to be predictive of poor surgical outcomes following minimally invasive discectomy. (ClinicalTrials.gov number: NCT01997086).

Power control of CiADS core with the intensity of the proton beam

Kai Yin,Wenjing Ma,Wenjuan Cui,Zhiyong He,Xinxin Li,Shiwu Dang,Feng Yang,Yuhui Guo,Limin Duan,Meng Li,Yikai Hou 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.4

This paper reports the control method for the core power of the China initiative Accelerator DrivenSystem (CiADS) facility. In the CiADS facility, an intense external neutron source provided by a protonaccelerator coupled to a spallation target is used to drive a sub-critical reactor. Without any control rodinside the sub-critical reactor, the core power is controlled by adjusting the proton beam intensity. Inorder to continuously change the beam intensity, an adjustable aperture is considered to be used at theLow Energy Beam Transport (LEBT) line of the accelerator. The aperture size is adjusted based on theProportional Integral Derivative (PID) controllers, by comparing either the setting beam intensity or thesetting core power with the measured value. To evaluate the proposed control method, a CiADS coremodel is built based on the point reactor kinetics model with six delayed neutron groups. The simulations based on the CiADS core model have indicated that the core power can be controlled stably byadjusting the aperture size. The response time in the adjustment of the core power depends mainly onthe adjustment time of the beam intensity

Measurement of TOF of fast neutrons with ²³⁸U target

Li, Meng,Guan, Yuanfan,Lu, Chengui,Zhang, Junwei,Yuan, Xiaohua,Duan, Limin,Yang, Herun,Hu, Rongjiang,He, Zhiyong,Wei, Xianglun,Ma, Peng,Gan, Zaiguo,Yang, Chunli,Zhang, Hongbin,Chen, Liang,Qiu, Tianli Korean Nuclear Society 2021 Nuclear Engineering and Technology Vol.53 No.6

We developed a Dual-PPACs detector for fast neutron measurements that consists of two sets of PPAC: conventional PPAC and fission PPAC. A²³⁸U(U₃O₈) coating is placed in the fission PPAC's anode, which is used as the neutrons conversion layer. An experiment was performed to measure neutron time-of-flight (TOF) in which ²⁵²Cf spontaneous fission source was used. An excellent time resolution of 164ps has been observed at 6 mbar in isobutene gas. With the excellent time resolution of Dual-PPACs detector, exact neutron energy can be extracted from the timing measurement. The experimental detection efficiency was 1.9 × 10^-7, consistent with the efficiency of 2.5 × 10^-7 given by a Geant4 simulation. Ultimately, the results show that the Dual-PPACs detector is a suitable candidate for measuring fast neutrons in the future CiADS system.

A rapid and quantitative fluorescent microsphere immunochromatographic strip test for detection of antibodies to porcine reproductive and respiratory syndrome virus

Yanqiu Wei,Baozhi Yang,Yunlong Li,Yongcheng Duan,Deyu Tian,Baoxiang He,Chuangfu Chen,Wenjun Liu,Limin Yang 대한수의학회 2020 Journal of Veterinary Science Vol.21 No.4

A fluorescent microsphere-based immunochromatographic strip test (FICT) was developed for the rapid, sensitive, and quantitative detection of porcine reproductive and respiratory syndrome virus (PRRSV) antibodies at the pen-side. The assay was based on the formation of a sandwich immune-complex (anti-pig IgG-PRRSV antibodies-NSP7/N), which was validated by a comparison with IDEXX-ELISA using 3325 clinical specimens. The diagnostic specificity, sensitivity, and accuracy of FICT were 97.28, 93.41, and 94.95%, respectively. FICT showed a good correlation with the virus neutralization assay. Overall, a promising pen-side diagnostic tool was developed for the rapid and quantitative detection of PRRSV antibodies within 15 min.