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1.
Proc Natl Acad Sci U S A ; 121(9): e2316580121, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38377204

ABSTRACT

Achieving high-performance materials with superior mechanical properties and electrical conductivity, especially in large-sized bulk forms, has always been the goal. However, it remains a grand challenge due to the inherent trade-off between these properties. Herein, by employing nanodiamonds as precursors, centimeter-sized diamond/graphene composites were synthesized under moderate pressure and temperature conditions (12 GPa and 1,300 to 1,500 °C), and the composites consisted of ultrafine diamond grains and few-layer graphene domains interconnected through covalently bonded interfaces. The composites exhibit a remarkable electrical conductivity of 2.0 × 104 S m-1 at room temperature, a Vickers hardness of up to ~55.8 GPa, and a toughness of 10.8 to 19.8 MPa m1/2. Theoretical calculations indicate that the transformation energy barrier for the graphitization of diamond surface is lower than that for diamond growth directly from conventional sp2 carbon materials, allowing the synthesis of such diamond composites under mild conditions. The above results pave the way for realizing large-sized diamond-based materials with ultrahigh electrical conductivity and superior mechanical properties simultaneously under moderate synthesis conditions, which will facilitate their large-scale applications in a variety of fields.

2.
Small ; 20(22): e2309501, 2024 May.
Article in English | MEDLINE | ID: mdl-38109067

ABSTRACT

The development of lithium-based solid-state batteries (SSBs) has to date been hindered by the limited ionic conductivity of solid polymer electrolytes (SPEs), where nonsolvated Li-ions are difficult to migrate in a polymer framework at room temperature. Despite the improved cationic migration by traditional heating systems, they are far from practical applications of SSBs. Here, an innovative strategy of light-mediated energy conversion is reported to build photothermal-based SPEs (PT-SPEs). The results suggest that the nanostructured photothermal materials acting as a powerful light-to-heat converter enable heating within a submicron space, leading to a decreased Li+ migration barrier and a stronger solid electrolyte interface. Via in situ X-ray diffraction analysis and molecular dynamics simulation, it is shown that the generated heating effectively triggers the structural transition of SPEs from a highly crystalline to an amorphous state, that helps mediate lithium-ion transport. Using the assembled SSBs for exemplification, PT-SPEs function as efficient ion-transport media, providing outstanding capacity retention (96% after 150 cycles) and a stable charge/discharge capacity (140 mA g-1 at 1.0 C). Overall, the work provides a comprehensive picture of the Li-ion transport in solid polymer electrolytes and suggests that free volume may be critical to achieving high-performance solid-state batteries.

3.
Phys Chem Chem Phys ; 26(23): 16459-16465, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38832399

ABSTRACT

Developing high-loading spin-polarized p-block-element-based single-atom catalysts (p-SACs) upon defect-free substrates for various chemical reactions wherein spin selection matters is generally considered a formidable challenge because of the difficulty of creating high densities of underpinning stable defects and the delocalized electronic features of p-block elements. Here our first-principles calculations establish that the defect-free rutile TiO2(110) wide-bandgap semiconducting anchoring support can stabilize and localize the wavefunctions of p-block metal elements (Sb and Bi) via strong ionic bonding, forming spin-polarized p-SACs. Cooperated by the underlying d-block Ti atoms via a delicate spin donation-back-donation mechanism, the p-block single-atom reactive center Sb(Bi) exhibits excellent catalysis for spin-triplet O2 activation and CO oxidation in alignment with Wigner's spin selection rule, with a low rate-limiting reaction barrier of ∼0.6 eV. This work is crucial in establishing high-loading reactive centers of high-performance p-SACs for various important physical processes and chemical reactions, especially wherein the spin degree of freedom matters, i.e., spin catalysis.

4.
J Phys Chem A ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159008

ABSTRACT

Material stability is the focus on both experiments and calculations, which includes the energetic stability at the static state and the thermodynamic stability at the kinetic state. To show whether energetics or kinetics dominates on material stability, this study focuses on the Pd13 clusters, because of their observable magnetic moment in experiment. Energetically, the CALYPSO searching method and first-principles calculations find that Pd13(C2) is the ground state at 0 K while the static frequency calculations demonstrate that the icosahedron Pd13(Ih) becomes more favorable on free energy as temperature increases. However, their magnetic moments (8 µB) are not in agreement with the experimental value (<5.2 µB). Kinetically, ab initio molecular dynamics simulations reveal that Pd13(C3v) (6 µB) has supreme isomerization temperature and the other 11 low-lying isomers transform to Pd13(C3v) directly or indirectly, demonstrating that Pd13(C3v) has the maximum probability to be observed in experiment. The magnetic moment difference between experiment (<5.2 µB) and this calculation (6 µB) may be due to the spin multiplicities. Our result suggests that the magnetic moment disparity between theory and experiment (in Pd13 clusters) originates from the kinetic stability.

5.
Eur Spine J ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39134698

ABSTRACT

OBJECTIVE: To investigate the anatomical indexes and anatomical positional indexes of the atlantoaxial synchondroses in normal Chinese Han children aged 1-6 years, and to analyze the changing law of the atlantoaxial cartilage union with the growth and development of age and its influence on the atlantoaxial ossification in children. METHODS: A retrospective collection of CT imaging of 160 cases of normal cervical spine in children aged 1 to 6 years old was conducted. The cases were divided into six age groups, with each group representing a one-year age range. Measure the morphological anatomical indicators and anatomical positional indicators of the atlantoaxial synchondroses. Record and statistically analyze the measurements of each indicator. RESULTS: Measurements were taken on various parameters of the atlantoaxial synchondroses. TD, SD, height, area, and perimeter all gradually decreased among the groups. Distance between bilateral atlantal anterolateral synchondroses increased gradually from Group A to Group F, while the angle formed along the long axis in the cross-section showed a decreasing trend. Distance between the axoid dentolateral synchondroses and between the neurocentral synchondroses increased gradually from Group A to Group F, with the angle value in the cross-section showing a gradual decrease, and distance from the odontoid apex increasing from Group A to Group F. CONCLUSIONS: The atlantoaxial synchondroses gradually decrease in size with age, and ossification levels increase with age, with faster ossification occurring during a 1-2 years-old period. The anterolateral synchondroses, dentolateral synchondroses, and neurocentral synchondroses all gradually ossify towards the lateral direction with increasing age.

6.
Nano Lett ; 23(17): 8241-8248, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37594857

ABSTRACT

Next-generation mid-infrared (MIR) imaging chips demand free-cooling capability and high-level integration. The rising two-dimensional (2D) semimetals with excellent infrared (IR) photoresponses are compliant with these requirements. However, challenges remain in scalable growth and substrate-dependence for on-chip integration. Here, we demonstrate the inch-level 2D palladium ditelluride (PdTe2) Dirac semimetal using a low-temperature self-stitched epitaxy (SSE) approach. The low formation energy between two precursors facilitates low-temperature multiple-point nucleation (∼300 °C), growing up, and merging, resulting in self-stitching of PdTe2 domains into a continuous film, which is highly compatible with back-end-of-line (BEOL) technology. The uncooled on-chip PdTe2/Si Schottky junction-based photodetector exhibits an ultrabroadband photoresponse of up to 10.6 µm with a large specific detectivity. Furthermore, the highly integrated device array demonstrates high-resolution room-temperature imaging capability, and the device can serve as an optical data receiver for IR optical communication. This study paves the way toward low-temperature growth of 2D semimetals for uncooled MIR sensing.

7.
Angew Chem Int Ed Engl ; : e202403618, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819600

ABSTRACT

The sulfur reduction reaction (SRR) is an attractive 16-electron transfer process that endows Li-S batteries with a theoretical capacity of 1,672 mAh g-1. However, the slow kinetics and complex pathways of the SRR cause the shuttling of soluble polysulfides (PSs), thus fast capacity fading. Here, we report using cisplatin (cis-Pt) as a novel mediator to improve the SRR kinetics and a molecular probe to identify the SRR pathways. We show that cis-Pt with a reductive Pt2+ center can directly slice the S-S bonds of PSs, leading to enhanced charge transfer kinetics, guided SRR pathways, and depth conversion of PSs to Li2S. With cis-Pt added, Li-S coin cells deliver a maximum specific capacity of 1,437 mAh g-1 and a capacity decay of 0.017% per cycle after 1000 cycles, while a pouch cell with a practical electrolyte-sulfur ratio (2.5 µl mg-1) exhibits a high energy density of 318.8 Wh kg-1. Our mechanistic studies reveal that cis-Pt steers the cathodic SRR pathways by generating redox active cis-Pt/PSs complexes, enabling the replacement of the sluggish SRR with a faster redox cycling of Pt4+/Pt2+ pairs. These findings provide insights into the rational design of functional mediators for tackling the cathodic challenges inside Li-S batteries.

8.
Appl Microbiol Biotechnol ; 107(12): 3955-3966, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37166480

ABSTRACT

Fusion tag technology is an important tool for rapid separation, purification, and characterization of proteins. Combined with monoclonal antibodies, tag epitope systems can be rapidly adapted to many assay systems. A monoclonal antibody that reacts with the matrix protein of the rabies virus CVS-11 strain was reported. The epitope (termed M) targeted by this antibody contains only six amino acids. We examine whether this specific sequence epitope can be applied as a protein tag. We show ectopic expression of M-tagged proteins has little impact on cell viability or major signaling pathways. The M tag system can be used for western blotting, immunoprecipitation, immunofluorescence staining, and flow cytometry assays. The results indicate the specificity, sensitivity, and versatility of this novel epitope tag system are comparable to the widely used FLAG tag system, providing researchers with an additional tool for molecular analysis. KEY POINTS: • A short peptide (Pro Pro Tyr Asp Asp Asp) can be applied as a new tag. • The new epitope-tagging fusion system has no effect on the main cellular signaling pathway. • The epitope-tagging fusion system can be widely used for western blotting, immunoprecipitation, immunofluorescence, flow cytometry, etc.


Subject(s)
Rabies virus , Epitopes , Rabies virus/genetics , Peptides/metabolism , Antibodies, Monoclonal , Blotting, Western
9.
Nano Lett ; 22(9): 3744-3750, 2022 May 11.
Article in English | MEDLINE | ID: mdl-35437988

ABSTRACT

Deciphering the precise physical mechanism of interaction between an adsorbed species and a reactive site in heterogeneous catalysis is crucial for predictive design of highly efficient catalysts. Here, using first-principles calculations we identify that the two-dimensional ferromagnetic metal organic framework of Mn2C18H12 can serve as a highly efficient single-atom catalyst for spin-triplet O2 activation and CO oxidation. The underlying mechanism is via "concerted charge-spin catalysis", involving a delicate synergetic process of charge transfer, provided by the hosting Mn atom, and spin selection, preserved through active participation of its nearest neighboring Mn atoms for the crucial step of O2 activation. The synergetic mechanism is further found to be broadly applicable in O2 adsorption on magnetic X2C18H12 (X = Mn, Fe, Co, and Ni) with a well-defined linear scaling dependence between the chemical activity and spin excitation energy. The present findings provide new insights into chemical reactions wherein spin selection plays a vital role.

10.
Mol Genet Genomics ; 297(6): 1755-1765, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36152077

ABSTRACT

The rise of the Tubo Kingdom is considered as the key period for the formation of modern groups on the Tibetan Plateau. The ethnic origin of the residents of the Tubo Kingdom is quite complex, and their genetic structure remains unclear. The tombs of the Tubo Kingdom period in Dulan County, Qinghai Province, dating back to the seventh century, are considered to be the remains left by Tubo conquerors or the Tuyuhun people dominated by the Tubo Kingdom. The human remains of these tombs are ideal materials for studying the population dynamics in the Tubo Kingdom. In this paper, we analyzed the genome-wide data of eight remains from these tombs by shotgun sequencing and multiplex PCR panels and compared the results with data of available ancient and modern populations across East Asia. Genetic continuity between ancient Dulan people with ancient Xianbei tribes in Northeast Asia, ancient settlers on the Tibetan Plateau, and modern Tibeto-Burman populations was found. Surprisingly, one out of eight individuals showed typical genetic features of populations from Central Asia. In summary, the genetic diversity of ancient Dulan people and their affiliations with other populations provide an example of the complex origin of the residents in the Tubo Kingdom and their long-distance connection with populations in a vast geographic region across ancient Asia.


Subject(s)
DNA, Ancient , Genetics, Population , Humans , Tibet , Asian People/genetics , Ethnicity , Genetic Variation/genetics
11.
Pediatr Blood Cancer ; 69(9): e29842, 2022 09.
Article in English | MEDLINE | ID: mdl-35758531

ABSTRACT

BACKGROUND: There are no international standards or normalizations for diagnosing and treating complications from blood transfusions. We comprehensively compared the incidence of adverse blood transfusions in children and adults. METHODS: Available literature on blood transfusion adverse reactions in children and adults prior to November 27, 2021 was collected from several electronic databases. This meta-analysis was performed using Revman 5.2 and Stata 15.1. RESULTS: The incidence of transfusion reactions is higher in children than in adults. Children transfused with red blood cells and platelets exhibited a higher incidence of transfusion reaction than that of adults. Moreover, the incidence of allergic and febrile non-hemolytic transfusion reactions was significantly higher in children than in adults. The incidence of some rare transfusion reactions was also significantly higher in children than in adults. CONCLUSION: The incidence of transfusion reactions in children and adults is varied. Guidelines for children are necessary.


Subject(s)
Hypersensitivity , Transfusion Reaction , Adult , Blood Transfusion , Child , Erythrocytes , Humans , Hypersensitivity/complications , Hypersensitivity/epidemiology , Incidence , Transfusion Reaction/epidemiology , Transfusion Reaction/etiology
12.
Phys Chem Chem Phys ; 24(29): 17832-17840, 2022 Jul 27.
Article in English | MEDLINE | ID: mdl-35851386

ABSTRACT

Hydrogen energy is considered to be one of the most promising clean energy sources. The development of highly active, low-cost catalysts, and good stability is essential for hydrogen production. Herein, the catalytic activity of a two-dimensional ß-Sb surface doped with main-group elements (N, P, As, O, S, Se, and Te) for the hydrogen evolution reaction (HER) was investigated by density functional theory, and the catalytic activity of the ß-Sb monolayer can be improved by doping group VIA atoms. The catalytic activity of Se@Sb and O@Sb structures at the doping concentration of 2.78% and the S@Sb structure at the doping concentration of 5.56% may be as good as the Pt(111) surface, while keeping energetically stable. In addition, the catalytic performance could be optimized under biaxial strain. Further analysis suggests that the activity is caused by hole states in the lone pair electrons, which are created by the group VIA atom dopants. And our work also reveals that the density of states at the Fermi level could be an appropriate descriptor of the hydrogenation Gibbs free energy. This work not only proposes a novel non-platinum HER catalyst but also provides physical foundations for further application on antimonene-based catalysts.

13.
Metab Brain Dis ; 37(7): 2417-2429, 2022 10.
Article in English | MEDLINE | ID: mdl-35819709

ABSTRACT

CDGSH iron sulfur domain 2 (Cisd2) is known as a key determinant factor in maintaining cellular homeostasis. However, whether Cisd2 contributes to the mediation of neuronal injury during ischemic stroke has not been well stressed. This work focuses on investigating the role of Cisd2 in regulating neuronal injury caused by oxygen-glucose deprivation/reoxygenation (OGD/R). The dramatic down-regulation of Cisd2 was observed in hippocampal neurons suffering from OGD/R injury. In Cisd2-overexpressed neurons, OGD/R-induced neuronal apoptosis, oxidative stress and inflammation were prominently mitigated. Further investigation uncovered that the forced expression of Cisd2 reinforced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in OGD/R-exposed neurons. Moreover, the overexpression of Cisd2 enhanced Akt activation, and the restraint of Akt abolished Cisd2-induced Nrf2 activation. Importantly, restraint of Nrf2 reversed Cisd2-conferred neuroprotective effects in OGD/R-exposed neurons. Taken together, our findings indicate that Cisd2 is able to protect neurons from OGD/R-induced injuries by strengthening Nrf2 activation via Akt. Our work identifies Cisd2 as a potential determinant factor for neuronal injury during cerebral ischemia/reperfusion injury.


Subject(s)
Neuroprotective Agents , Reperfusion Injury , Humans , Apoptosis , Glucose/metabolism , Hippocampus/metabolism , Iron/metabolism , Neurons/metabolism , Neuroprotective Agents/pharmacology , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Oxygen/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion Injury/metabolism , Signal Transduction , Sulfur/metabolism , Sulfur/pharmacology
14.
Mar Drugs ; 20(1)2022 Jan 12.
Article in English | MEDLINE | ID: mdl-35049921

ABSTRACT

As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a drug delivery system. In this paper, a novel alginate lyase, Algpt, was cloned and characterized from a marine bacterium, Paenibacillus sp. LJ-23. The purified enzyme was composed of 387 amino acid residues, and had a molecular weight of 42.8 kDa. The optimal pH of Algpt was 7.0 and the optimal temperature was 45 °C. The analysis of the conserved domain and the prediction of the three-dimensional structure indicated that Algpt was a novel alginate lyase. The dominant degradation products of Algpt on alginate were AOS dimer to octamer, depending on the incubation time, which demonstrated that Algpt degraded alginate in an endolytic manner. In addition, Algpt was a salt-independent and thermo-tolerant alginate lyase. Its high stability and wide adaptability endow Algpt with great application potential for the efficient preparation of AOS with different sizes and AOS-based products.


Subject(s)
Alginates/chemistry , Lyases/chemistry , Paenibacillus/genetics , Animals , Aquatic Organisms , China , Cloning, Molecular , Drug Delivery Systems
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(6): 637-640, 2022 Jun 10.
Article in Zh | MEDLINE | ID: mdl-35773771

ABSTRACT

OBJECTIVE: To investigate the molecular mechanism of B antigen weaken expression in 4 cases of ABO blood group samples. METHODS: ABO blood group phenotypes were detected by micro-column gel method and saline test tube method. Exon 1-7 and promoter region of the ABO gene were amplified by polymerase chain reaction (PCR) and PCR products were directly sequenced. RESULTS: Mixed agglutination occurs between RBC and B antibody in all the 4 samples. Three patients were identified as ABweak phenotype, and the mother of the patient ID 2 was identified as Bweak. Direct sequencing and pedigree analysis showed that there were -35 to -18 del GGCGGAAGGCGGAGGCCG mutation in the B allele of 3 samples and C>T mutation in -119 base site of one sample in promoter regions. CONCLUSION: The promoter of ABO gene plays an important role in the normal expression of ABO blood group, and the mutation of the promoter can lead to the decreased expression of ABO blood group antigen. In this study, a new abnormal mutation (C>T of -119 base site) in the promoter was found, which should be concerned.


Subject(s)
ABO Blood-Group System , Nucleotides , ABO Blood-Group System/genetics , Alleles , Genotype , Mutation , Phenotype , Promoter Regions, Genetic
16.
Exp Cell Res ; 391(1): 111988, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32251645

ABSTRACT

Tripartite motif 16 (TRIM16) has emerged as a novel oxidative stress-responsive protein that confers cytoprotective effects by reinforcing the cellular antioxidant system. However, whether TRIM16 is involved in regulating oxidative stress during cerebral ischemia/reperfusion injury remains unclear. In the present study, we aimed to explore the potential function and molecular mechanism of TRIM16 in regulating oxidative stress in neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Here, we found that OGD/R exposure resulted in a significant induction of TRIM16 expression in neurons. Depletion of TRIM16 by siRNA-mediated gene knockdown markedly upregulated the sensitivity of neurons to OGD/R-induced apoptosis and reactive oxygen species (ROS) generation. Notably, upregulation of TRIM16 expression significantly alleviated OGD/R-induced apoptosis and ROS generation in neurons. Moreover, TRIM16 overexpression markedly increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression and enhanced Nrf2/antioxidant response element (ARE) activation associated with downregulation of kelch-like ECH-associated protein 1 (Keap1) expression. Restoration of Keap1 significantly reversed the TRIM16-mediated promotion effect on Nrf2/ARE activation. In addition, knockdown of Nrf2 also markedly abrogated the TRIM16-conferred neuroprotective effect in OGD/R-exposed neurons. Taken together, our results of our study demonstrate that induction of TRIM16 confers a cytoprotective effect in OGD/R-exposed neurons through enhancement of Nrf2/ARE antioxidant signaling via downregulation of Keap1. These findings suggest that TRIM16 may play a critical role in cerebral ischemia/reperfusion injury and serve as a promising target for neuroprotection.


Subject(s)
Antioxidants/metabolism , Kelch-Like ECH-Associated Protein 1/biosynthesis , NF-E2-Related Factor 2/metabolism , Neuroprotection/physiology , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Anaerobiosis , Animals , Apoptosis/physiology , Cell Line , Glucose/metabolism , Hippocampus/cytology , Hippocampus/metabolism , Hypoxia, Brain/pathology , Mice , Neurons/metabolism , Oxidative Stress/physiology , RNA Interference , RNA, Small Interfering/genetics , Reactive Oxygen Species/metabolism , Signal Transduction/physiology , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/genetics
17.
J Phys Chem A ; 124(22): 4325-4332, 2020 Jun 04.
Article in English | MEDLINE | ID: mdl-32390419

ABSTRACT

Identification of the geometric structures of silver clusters is of great importance in future nanotechnologies due to their superior properties. Nevertheless, some ground-state structures are still in academic debate, partly because the experiments and theoretical calculations are not performed at the same temperatures. For example, silver clusters usually have compact configurations. However, a combined experimental and theoretical study proposed that the most stable structure of Ag13- had a two-coordinated atom. By using the CALYPSO approach for the global minima search followed by first-principles calculations, we discovered that a more compact trilayer Ag13- cluster was the ground state, in accordance with another three works published recently. In addition, its O2 adsorption structure is also energetically favored. By tracing characteristic bond changes in ab initio molecular dynamics (MD) simulations, we confirmed that, compared with other isomers, this trilayer structure and its O2 adsorption structure also had the highest thermal stability. This work emphasized the thermal stability concept in theoretical calculations, which may be a necessary supplement to explain the experimental observations on cluster science.

18.
Clin Exp Hypertens ; 42(2): 167-170, 2020.
Article in English | MEDLINE | ID: mdl-30978117

ABSTRACT

Objectives: The involvement of oxidative stress in the pathophysiology of preeclampsia (PE) has been already suggested. In this present study, we aimed to investigate the association of the genetic frequency of heme oxygense-1 (HMOX1) polymorphism with PE in Chinese Han women.Methods: We researched the genetic distribution of rs2071746 polymorphism in HMOX1 by the TaqMan allelic discrimination real-time PCR between 1235 PE patients and 1720 healthy women.Results: We found there were't significant differences in the distribution of HMOX1 rs2071746 polymorphism in PE compared to the control group (rs2071746, genotype χ2 = 0.282, P = 0.869 and allele χ2 = 0.027, P = 0.869, OR = 1.009, 95% = 0.909-1.120).Conclusion: The rs2071746 polymorphism in HMOX1 might not be related to PE in Chinese women, although further investigations should be conducted to confirm our findings.


Subject(s)
Heme Oxygenase-1/genetics , Pre-Eclampsia/genetics , Adult , Alleles , Asian People/genetics , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , Hypertension/genetics , Polymorphism, Single Nucleotide , Pregnancy , Real-Time Polymerase Chain Reaction
19.
J Biol Chem ; 293(9): 3321-3334, 2018 03 02.
Article in English | MEDLINE | ID: mdl-29348176

ABSTRACT

The 1555A→G mutation in mitochondrial 12S rRNA has been associated with aminoglycoside-induced and non-syndromic deafness in many individuals worldwide. Mitochondrial genetic modifiers are proposed to influence the phenotypic expression of m.1555A→G mutation. Here, we report that a deafness-susceptibility allele (m.4317A→G) in the tRNAIle gene modulates the phenotype expression of m.1555A→G mutation. Strikingly, a large Han Chinese pedigree carrying both m.4317A→G and m.1555A→G mutations exhibited much higher penetrance of deafness than those carrying only the m.1555A→G mutation. The m.4317A→G mutation affected a highly conserved adenine at position 59 in the T-loop of tRNAIle We therefore hypothesized that the m.4317A→G mutation alters both structure and function of tRNAIle Using lymphoblastoid cell lines derived from members of Chinese families (three carrying both m.1555A→G and m.4317A→G mutations, three harboring only m.1555A→G mutation, and three controls lacking these mutations), we found that the cell lines bearing both m.4317A→G and m.1555A→G mutations exhibited more severe mitochondrial dysfunctions than those carrying only the m.1555A→G mutation. We also found that the m.4317A→G mutation perturbed the conformation, stability, and aminoacylation efficiency of tRNAIle These m.4317A→G mutation-induced alterations in tRNAIle structure and function aggravated the defective mitochondrial translation and respiratory phenotypes associated with the m.1555A→G mutation. Furthermore, mutant cell lines bearing both m.4317A→G and m.1555A→G mutations exhibited greater reductions in the mitochondrial ATP levels and membrane potentials and increasing production of reactive oxygen species than those carrying only the m.1555A→G mutation. Our findings provide new insights into the pathophysiology of maternally inherited deafness arising from the synergy between mitochondrial 12S rRNA and tRNA mutations.


Subject(s)
Deafness/genetics , Mutation , Phenotype , RNA, Mitochondrial/genetics , RNA, Ribosomal/genetics , RNA, Transfer, Ile/genetics , Adenosine Triphosphate/biosynthesis , Alleles , Case-Control Studies , Cell Respiration/genetics , Cohort Studies , Deafness/metabolism , Deafness/pathology , Electron Transport Chain Complex Proteins/metabolism , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Mitochondria/genetics , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Young Adult
20.
J Obstet Gynaecol Res ; 43(10): 1578-1584, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28708319

ABSTRACT

AIM: The aim of the current study was to investigate whether iodized oil (IO) enhances high-intensity focused ultrasound (HIFU) ablation of uterine leiomyoma and to determine the features of hyperechoic changes in the target region. METHODS: Forty samples of uterine leiomyoma were randomly divided into an experimental group and a control group. In the experimental group, the leiomyoma was ablated by HIFU 30 min after 1 mL of iodized oil had been injected into the center of the myoma. The hyperechoic values and areas in the target region were observed by B-modal ultrasound after HIFU ablation. The samples were cut successively into slices and stained by triphenyltetrazolium chloride (TTC) solution within 1 h after HIFU ablation. The diameters of TTC-non-stained areas were measured and tissues in the borderline of the TTC-stained and -non-stained areas were observed pathologically. All procedures in the control group were the same as those in the experimental group except IO was replaced by physiological saline. RESULTS: The hyperechoic value in the target region in the experimental group was higher than that in the control group 4 min after HIFU ablation (P < 0.05). Hyperechoic areas in the target region as well as TTC-non-stained volumes in the experimental group were greater than those in the control group (P < 0.05). Routine pathologic observation showed that coagulation necrosis of leiomyoma occurred in the target region in both groups. CONCLUSION: IO causes coagulation necrosis, enlarges tissue damage, and postpones the attenuation of hyperechoic changes in the target region when HIFU ablation is carried out for leiomyoma in vitro.


Subject(s)
Contrast Media/therapeutic use , High-Intensity Focused Ultrasound Ablation/methods , Iodized Oil/therapeutic use , Leiomyoma/therapy , Uterine Neoplasms/therapy , Contrast Media/adverse effects , Female , Humans , In Vitro Techniques , Iodized Oil/adverse effects
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