Efficient Proton Conductor Based on Bismuth Oxide Clusters and Polyoxometalates.

Developing new solid-state electrolyte materials for improving the proton conductivity remains an important challenge. Herein, a novel two-dimensional layered solid-state proton conductor Bi2O2-SiW12 nanocomposite, based on silicotungstic acid (H4SiW12O40) and Bi(NO3)3·5H2O, was synthesized and characterized. The composite consists of a layered cation framework [Bi2O2]2+ and interlayer-embedded counteranionic [SiW12O40]4-, which forms continuous hydrogen bond (O-H···O) networks through the interaction of adjacent oxygen atoms on the surface of the [Bi2O2]2+ and oxygen atoms of the H4SiW12O40. Facile proton transfer along these pathways endows the Bi2O2-SiW12 (30:1) nanocomposite with an excellent proton conductivity of 3.61 mS cm-1 at 90 °C and 95% relative humidity, indicating that the nanocomposite has good prospects as a highly efficient proton conductor.

Association between urinary methylparaben level and bone mineral density in children and adolescents aged 8-19 years.

Previous epidemiological study has explored a positive association between methylparaben (Mep) and bone mineral density (BMD) in adults. Evidence linking Mep and BMD in children and adolescents is very limited. This study examined the association between Mep and BMD in children and adolescents aged 8-19 years. In this cross-sectional study, 1830 children and adolescents aged 8-19 years from NHANES 2011-2016 were analyzed. Mep was ln-transformed for analysis of the skewed distribution. Multiple linear regression analyses were performed to evaluate Mep's association with BMD (containing total BMD, trunk bone BMD, pelvis BMD, lumbar spine BMD, and thoracic spine BMD). Moreover, a generalized additive model (GAM) and a fitted smoothing curve (penalized spline method) were conducted to explore the exact shape of curve between them. In the fully adjusted model, ln-transformed Mep and BMD showed an independent and positive association (total BMD (ß = 0.003, 95% CI (0.001, 0.005), P = 0.01), trunk bone BMD (ß = 0.002, 95% CI (0.000, 0.005), P = 0.04), pelvis BMD (ß = 0.004, 95% CI (0.001, 0.008), P = 0.02), lumbar spine BMD (ß = 0.005, 95% CI (0.001, 0.008), P = 0.01), thoracic spine BMD (ß = 0.003, 95% CI (0.001, 0.005), P = 0.02)) and a linear association. Subgroup analysis showed positive association between ln-transformed Mep and BMD. Furthermore, the positive association was significant in females and children aged 12-19 years (P for trend < 0.05). This study is the first study to find evidence demonstrating that exposure to Mep may be positively associated with BMD in children and adolescents aged 8-19 years. Validation of our findings will need further research.

Prenatal diagnosis of paternal uniparental disomy for chromosome 2 in two fetuses with intrauterine growth restriction.

Uniparental disomy (UPD) is when all or part of the homologous chromosomes are inherited from only one of the two parents. Currently, UPD has been reported to occur for almost all chromosomes. In this study, we report two cases of UPD for chromosome 2 (UPD2) encountered during prenatal diagnosis. The ultrasound findings of the fetuses from two unrelated families showed intrauterine growth restriction. The karyotype analyses were normal. The two fetuses both had complete paternal chromosome 2 uniparental disomy detected by whole-exome sequencing, but their clinical outcomes were significantly different, with fetal arrest in case 1 and birth in case 2. In this report, we analyzed and discussed the phenotypes of the fetuses in these two cases and reviewed the literature on UPD2.

Hourglass shaped polyoxometalate-based materials as electrochemical sensors for the detection of trace Cr(VI) in a wide pH range.

Due to Chromium hexavalent Cr(VI) is one of the most carcinogenic toxic ions, it is essential for finding a low-cost, efficient and highly selective detection method. Considering the wide range of pH detection in water, a major issue is exploring high sensitive electrocatalyst. Thus, two crystalline materials with hourglass {P4Mo6} clusters in different metal centers were synthesized and had fabulous Cr(VI) detection performance in a wide pH range. At pH = 0, the sensitivities of CUST-572 and CUST-573 were 133.89 µA µM-1 and 30.05 µA µM-1, and the detection limits (LODs) of Cr(VI) were 26.81 nM and 50.63 nM which met World Health Organization (WHO) standard for drinking water. CUST-572 and CUST-573 also had good detection performance at pH = 1-4. In actual water samples, CUST-572 and CUST-573 also possessed sensitivities of 94.79 µA µM-1 and 20.09 µA µM-1 and LODs were 28.25 nM and 52.24 nM, showing high selectivity and chemical stability. The difference of the detection performance of CUST-572 and CUST-573 were mainly attributed to the interaction between {P4Mo6} and different metal centers of crystalline materials. In this work, electrochemical sensors for Cr(VI) detection in a wide pH range were explored, providing important guidance for the design of efficient electrochemical sensors for ultra-trace detection of heavy metal ions in practical environments.

Methyltransferase-like 3 enhances cell proliferation and cisplatin resistance in natural killer/T-cell lymphoma through promoting N6-methyladenosine modification and the stability of staphylococcal nuclease and Tudor domain-containing protein 1 mRNA.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is a typical class of non-Hodgkin's lymphoma, which is quite malignant because of its high resistance to chemotherapy. N6-methyladenosine (m6A) modification, a prevalent modification of eukaryotic RNA, was emerging as an important regulatory mechanism in progression of various tumors. Here, we demonstrated that methyltransferase-like 3 (METTL3), an RNA methyltransferase, was obviously upregulated in human NKTCL cell lines (NK-92, YTS, SNT-8, and SNK-6) compared with normal NK cells. Knockdown of METTL3 noticeably repressed proliferation and facilitated apoptosis in SNT-8 cells, whereas overexpression of METTL3 showed opposite results in SNK-6 cells. In the mechanism exploration, we found that METTL3 stimulated the m6A modification of staphylococcal nuclease and Tudor domain-containing protein 1 (SND1) mRNA, recruited YTH m6A RNA binding protein 1 to recognize the m6A site, thereby enhancing its mRNA stability. Rescue experiments demonstrated that METTL3 significantly prohibited NKTCL cell chemotherapy sensitivity to cisplatin (DDP) through regulating SND1 expression. Furthermore, knockdown of SND1 suppressed tumor growth and reduced DDP resistance in vivo . Taken together, our findings uncovered the role of METTL3 in the regulation of chemotherapy resistance in NKTCL oncogenesis.

Detection of four rare thalassemia variants using Single-molecule realtime sequencing.

Conventional methods for the diagnosis of thalassemia include gap polymerase chain reaction (Gap-PCR), reverse membrane hybridization (RDB), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. In this study, we used single molecule real-time technology (SMRT) sequencing and discovered four rare variants that have not been identified by conventional diagnostic methods for thalassemia. We also performed genotype and phenotype analyses on family members of thalassemia patients. The SMRT technology detected five cases in which the proband had abnormal results by conventional diagnostic methods or inconsistencies between the genotype and phenotype. The variants included two cases of an α-globin gene cluster 27,311 bp deletion, --27.3/αα (hg38 chr16:158664-185974), one case of an HS-40 region 16,079 bp deletion (hg38 chr16:100600-116678), one case of a rearrangement of -α3.7α1α2 on one allele and one case of a ß-globin gene cluster HBG1-HBG2 4,924 bp deletion (hg38 chr11:5249345-5254268). This study clarified the hematological phenotypes of four rare variants and indicated the application value of SMRT in the diagnosis of rare α-globin and ß-globin gene cluster deletions, gene recombination and deletion breakpoints. The SMRT method is a comprehensive one-step technology for the genetic diagnosis of thalassemia and is particularly suitable for the diagnosis of thalassemia with rare deletions or genetic recombination.

First-Time Diagnosis and Ultrasound Features of Extranodal Lymphoma in Children.

Objective: To assess the diagnostic value of ultrasound for extranodal lymphoma in children. Methods: In this retrospective study, the first diagnostic clinical manifestation, ultrasound sonograms, and puncture pathology of 40 cases of pediatric lymphoma treated in Xi'an Children's Hospital from August 2018 to March 2020 were analyzed. Results: The first diagnostic clinical manifestation varied from jaundice to gastrointestinal, motor, neurological, respiratory, circulatory skin, and soft tissue multisystem disorders. The intranodal ultrasound results showed abnormally enlarged lymph nodes with extranodal involvement of the liver, pancreas, spleen, kidney, ovaries, and mediastinum as hypoechoic masses with multiple plasma cavity effusions, and color Doppler flow imaging (CDFI) results showed abundant blood flow signals in the lesions. The pathological diagnosis by ultrasound-guided puncture was Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple subtypes. Conclusion: Routine ultrasound can provide an imaging basis for early identification and differential diagnosis of lymphoma, and ultrasound-guided puncture biopsy is simple, minimally invasive, and histopathological-based.

LINC00839 Promotes Neuroblastoma Progression by Sponging miR-454-3p to Up-Regulate NEUROD1.

Neuroblastoma (NB) is the most common extracranial solid malignancy in children. Increasing long non-coding RNAs (lncRNAs) are reported to be associated with NB tumorigenesis and aggressiveness. Here, we attempted to investigate the biological functions of LINC00839 in NB progression as well as its possible pathogenic mechanisms. Public microarray datasets were applied to unearth the abnormally expressed lncRNAs in NB. RT-qPCR analysis was used to measure the expression of LINC00839, miR-454-3p, and neuronal differentiation 1 (NEUROD1) mRNA. The protein level was determined by a western blot assay. CCK-8, plate clone formation, EdU, wound-healing scratch, and transwell assays were employed to evaluate cell proliferation, migration, and invasion. Xenografts were developed in nude mice to determine the effects of LINC00839 on NB tumor growth. Dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments were performed to identify the interaction between miR-454-3p and LINC00839 or NEUROD1. According to GSE datasets (GSE16237 and GSE16476), LINC00839 was found as a potential driver of NB progression. LINC00839 expression was higher in NB tumor tissues and cells. Also, LINC00839 expression was positively correlated with MYCN amplification, advanced INSS stages, and worse prognosis. Silencing of LINC00839 suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, LINC00839 could act as a sponge of miR-454-3p to facilitate the expression of its target NEUROD1. Moreover, miR-454-3p was demonstrated to exert an anti-cancer activity in NB. More importantly, the tumor-suppressive properties mediated by LINC00839 knockdown were significantly counteracted by the inhibition of miR-454-3p or overexpression of NEUROD1. Our study demonstrates that LINC00839 exerts an oncogenic role in NB through sponging miR-454-3p to up-regulate NEUROD1 expression, deepening our comprehension of lncRNA involved in NB and providing access to the possibility of LINC00839 as a therapeutic target for NB.

Licochalcone E inhibits trxR1 expression, alters Nrf2/STAT6 signal, and induces antitumor effects in vitro against human SH-SY5Y and SK-N-BE(2) neuroblastoma cells.

Neuroblastoma (NB) is the most common solid tumor of the sympathetic nervous system (SNS) arising in childhood less than 15 years age. Licochalcone (Lic) is known to show inhibitory effects in cancer growth, and there has evidence suggested that Lic A inhibits hypoxic induced NB SK-N-SH cell proliferation. However, it is unclear whether LicE exerts similar effects in NB and the associated molecular mechanism of Lic in neuroblastoma is still unclear. In the current study, we found that LicE at the concentration 2, 4 and 6 µM all induced a profound reduction in cell viability, colony formation and cell proliferation. Next, LicE treatment effectively promoted cell apoptosis, inhibited cell migration and invasion. LicE significantly suppressed trxR1 expression, activated Nrf2 expression and inhibited STAT6 expression in SH-SY5Y and SK-N-BE(2) NB cells. We further identified that trxR1, STAT6 overexpression or Nrf2 silence reversed the antitumor effects of LicE in human SH-SY5Y and SK-N-BE(2) NB cells. Finally, LicE treatment significantly inhibited tumor growth in nude mice carrying a SK-N-SH cell xenograft. These results provide new insights into the effects and highlighting a novel mechanism of LicE through regulating trxR1/Nrf2/STAT6 signal pathway in NB.

Hourglass-Type Polyoxometalate-Based Crystalline Material as an Efficient Proton-Conducting Solid Electrolyte.

Proton exchange membrane fuel cells are limited because they are limited to working temperatures and are susceptible to damage by dramatic electrochemical environments such as hydrogen peroxide/radicals. It is necessary to develop new proton-conducting materials that are water-stable and can operate at high temperatures. The hourglass reduced molybdophosphate-based compound (H2bimb)3[Zn3(H6P4Mo6O31)2] (bimb = 1,4-bis[(1H-imidazol-1-yl)methyl]benzene) was designed and synthesized under solvothermal conditions. Single-crystal X-ray diffraction analyses demonstrated noticeably that CUST-571 was composed of an hourglass {Zn[P4Mo6]2} structure, which consisted of two fully reduced half-units {P4Mo6}. It was found that CUST-571 possessed an excellent proton conductivity of 4.54 × 10-3 S cm-1 at 85 °C and 98% RH (relative humidity). In addition, CUST-571 is capable of an excellent catalytic decomposition of H2O2, which is beneficial to increase the life of fuel cells. On the basis of the aforementioned results, CUST-571 may be a promising proton-conducting polyoxometalate hybrid material in the future.

Precise Molecular-Level Modification of Nafion with Bismuth Oxide Clusters for High-performance Proton-Exchange Membranes.

Fabricating proton exchange membranes (PEMs) with high ionic conductivity and ideal mechanical robustness through regulation of the membrane microstructures achieved by molecular-level hybridization remains essential but challenging for the further development of high-performance PEM fuel cells. In this work, by precisely hybridizing nano-scaled bismuth oxide clusters into Nafion, we have fabricated the high-performance hybrid membrane, Nafion-Bi12 -3 %, which showed a proton conductivity of 386 mS cm-1 at 80 °C in aqueous solution with low methanol permeability, and conserved the ideal mechanical and chemical stabilities as PEMs. Moreover, molecular dynamics (MD) simulation was employed to clarify the structural properties and the assembly mechanisms of the hybrid membrane on the molecular level. The maximum current density and power density of Nafion-Bi12 -3 % for direct methanol fuel cells reached to 432.7 mA cm-2 and 110.2 mW cm-2 , respectively. This work provides new insights into the design of versatile functional polymer electrolyte membranes through polyoxometalate hybridization.

How the surfactants mixed with emulsion can enhance the sand-fixation ability in the high salt-affected sandy land.

In order to control the impacts of salt crystallization damage, in this article, the surfactant Pluronic L35 (L35, a nonionic surfactant), for the first time, was added into P(VAc-DBM-AA-SSS) emulsion to improve the ecological sand-fixing capability in high salt-affected sandy land. This study started from the analysis of salt tolerance of P(VAc-DBM-AA-SSS) film by scanning electron microscope (SEM) and mechanical property. Then, the surfactant L35 has been selected to study the effect on salt crystal behaviour before reaction with emulsion. The performance and morphology of adding varied L35 and 3% NaCl into P(VAc-DBM-AA-SSS) emulsion have been considered. In addition, sand-fixing properties (e.g. compressive strength and water retaining) of the emulsion mixed with L35 were evaluated. Finally, the influence of the emulsion mixed with L35 on the growth of plant was investigated for understanding its ecological effect. The experimental results showed that the L35 could change the morphology of salt in sand; moreover, adding L35 into P(VAc-DBM-AA-SSS) emulsion can visibly enhance the sand-fixing ability in high salt-affected sandy land. The investigation into the influence of the emulsion mixed with L35 on the growth of plant also showed a dependable ecological effect.

Early Onset of Combined Oxidative Phosphorylation Deficiency in Two Chinese Brothers Caused by a Homozygous (Leu275Phe) Mutation in the C1QBP Gene.

Mitochondrial diseases constitute a group of heterogeneous hereditary diseases caused by impairments in mitochondrial oxidative phosphorylation and abnormal cellular energy metabolism. C1QBP plays an important role in mitochondrial homeostasis. In this study, clinical, laboratory examinations, 12-lead electrocardiographic, ultrasonic cardiogram, and magnetic resonance imaging data were collected from four members of a Chinese family. Whole exome were amplified and sequenced for the proband. The structure of protein encoded by the mutation was predicted using multiple software programs. The proband was a 14-year old boy with myocardial hypertrophy, exercise intolerance, ptosis, and increased lactate. His 9-year old brother exhibited similar clinical manifestations while the phenomenon of ptosis was not as noticeable as the proband. The onset of this disease was in infancy in both cases. They were born after uneventful pregnancies of five generation blood relative Chinese parents. A homozygous mutation (Leu275Phe) in the C1QBP gene was identified in both brothers in an autosomal recessive inherited pattern. Their parents were heterozygous mutation carriers without clinical manifestations. We demonstrated that a homozygous C1QBP- P.Leu275Phe mutation in an autosomal recessive inherited mode of inheritance caused early onset combined oxidative phosphorylation deficiency 33 (COXPD 33) (OMIM:617713) in two brothers from a Chinese family.

Polyoxometalate-based electron transfer modulation for efficient electrocatalytic carbon dioxide reduction.

The electrocatalytic carbon dioxide (CO2) reduction reaction (CO2RR) involves a variety of electron transfer pathways, resulting in poor reaction selectivity, limiting its use to meet future energy requirements. Polyoxometalates (POMs) can both store and release multiple electrons in the electrochemical process, and this is expected to be an ideal "electron switch" to match with catalytically active species, realize electron transfer modulation and promote the activity and selectivity of the electrocatalytic CO2RR. Herein, we report a series of new POM-based manganese-carbonyl (MnL) composite CO2 reduction electrocatalysts, whereby SiW12-MnL exhibits the most remarkable activity and selectivity for CO2RR to CO, resulting in an increase in the faradaic efficiency (FE) from 65% (MnL) to a record-value of 95% in aqueous electrolyte. A series of control electrochemical experiments, photoluminescence spectroscopy (PL), transient photovoltage (TPV) experiments, and density functional theory (DFT) calculations revealed that POMs act as electronic regulators to control the electron transfer process from POM to MnL units during the electrochemical reaction, enhancing the selectivity of the CO2RR to CO and depressing the competitive hydrogen evolution reaction (HER). This work demonstrates the significance of electron transfer modulation in the CO2RR and suggests a new idea for the design of efficient electrocatalysts towards CO2RR.

SS30, a novel thioaptamer targeting CD123, inhibits the growth of acute myeloid leukemia cells.

AIMS: CD123 represents an important acute myeloid leukemia (AML) therapeutic target. CD123 aptamers may potentially serve as tumor-homing ligands with excellent affinity and specificity for AML targeted therapy, but their complexity, laborious preparation and nuclease digestion limited pharmacological application. The aim of this study was to develop the first CD123 thioaptamer to overcome these obstacles. MAIN METHODS: Flow cytometry was utilized to assess the binding specificity, affinity and anti-nuclease ability of thioaptamer. CCK8, Annexin-V/DAPI, and colony forming assays were used to evaluate the anti-cancer ability of thioaptamer in vitro. The tumor volume, weights, survival rate, H&E staining of organs, and serum level of organ damage biomarkers of animal model were applied to investigate the anti-cancer ability of thioaptamer in vivo. Furthermore, we explored the binding mechanism between thioaptamer and CD123. KEY FINDINGS: CD123 thioaptamer SS30 was able to bind to CD123 structure with high specificity in complex nuclease environment, the dissociation constant of 39.1 nM for CD123 peptide and 287.6 nM for CD123+ AML cells, while exhibiting minimal cross-reactivity to albumin. Furthermore, SS30 inhibited the proliferation and survival of AML cell lines and human AML blasts selectively in vitro (P < 0.01). In addition, SS30 prolonged the survival and inhibited tumor growth in a mouse xenograft tumor model in vivo. Of note, SS30 blocked the interaction between IL-3 and CD123, and decreased expression of p-STAT5 and p-AKT. SIGNIFICANCE: The proliferation inhibition and nuclease resistance ability of SS30 made it as a more promising functional molecule for AML targeted therapy.

[SLC22A5 gene mutation analysis and prenatal diagnosis for a family with primary carnitine deficiency].

OBJECTIVE: To carry out mutation analysis and prenatal diagnosis for a family affected with primary carnitine deficiency. METHODS: Genomic DNA of the proband was extracted from peripheral blood sample 10 days after birth. The 10 exons and intron/exon boundaries of the SLC22A5 gene were subjected to PCR amplification and Sanger sequencing. The proband's mother was pregnant again two years after his birth. Fetal DNA was extracted from amniocytes and subjected to PCR and Sanger sequencing. RESULTS: Tandem mass spectrometric analysis of the proband revealed low level of plasma-free carnitine whilst organic acids in urine was normal. Compound heterozygous SLC22A5 mutations c.1195C>T (inherited from his father) and c.517delC (inherited from his mother) were detected in the proband. Prenatal diagnosis has detected no mutation in the fetus. The plasma-free carnitine was normal after birth. CONCLUSION: Appropriate genetic testing and prenatal diagnosis can prevent further child with carnitine deficiency. The identification of c.517delC, a novel mutation, enriched the spectrum of SLC22A5 mutations.

[Clinical and genetic analysis of a child with Noonan syndrome].

OBJECTIVE: To identify potential mutation in a child clinically diagnosed as Noonan syndrome and to provide genetic counseling and prenatal diagnosis for his family. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents, and amniotic fluid was taken from the mother during the second trimester. Next generation sequencing (NGS) was used to screen potential mutations from genomic DNA. Suspected mutation was verified by Sanger sequencing. RESULTS: A heterozygous c.4A>G (p.Ser2Gly) mutation of the SHOC2 gene was identified in the patient but not among other family members including the fetus. CONCLUSION: The Noonan syndrome is probably caused by the c.4A>G mutation of the SHOC2 gene. NGS is helpful for the diagnosis of complicated genetic diseases. SHOC2 gene mutation screening is recommended for patient suspected for Noonan syndrome.

A bismuth oxide/graphene oxide nanocomposite membrane showing super proton conductivity and low methanol permeability.

Proton exchange membrane fuel cells are still limited as state-of-art proton exchange membranes perform poorly at high and low temperature and are easily damaged by harsh electrochemical conditions such as reactive peroxide species. One effective solution to this issue is to develop new types of proton conductive materials that are capable of working in a broad temperature range. A simple vacuum-assisted filtration method is employed to obtain a well-ordered new proton-conducting membrane by immobilizing nanosized bismuth oxide clusters [H6Bi12O16] (NO3)10·6(H2O) {H6Bi12O16} onto graphene oxide (GO) supports (named as {H6Bi12O16}/GO). {H6Bi12O16}/GO is stable in acidic media and has high proton conductivity over the temperature range from -40 to 80 °C. The proton conductivity of the {H6Bi12O16}/GO membrane is 0.564 S cm-1 at 80 °C in aqueous solution (in plane), and 0.1 S cm-1 at 80 °C and 97% RH (out of plane), respectively. Without loss of high proton conductivity, the membrane also exhibited 100-fold lower methanol permeability than a Nafion 117 membrane. Moreover, {H6Bi12O16}/GO displayed good catalytic decomposition of hydrogen peroxide and superior humidity response and recovery properties. These advantages mean that {H6Bi12O16}/GO holds great promise as a solid-state electrolyte that can potentially be applied in energy conversion devices in the future.

[Screening for spinal muscular atrophy mutation carriers among 4931 pregnant women from Liuzhou region of Guangxi].

OBJECTIVE: To screen for carriers of SMN1 gene mutation, which underlies spinal muscular atrophy (SMA), in 4931 pregnant women from Liuzhou region of Guangxi, and to determine the carrier rate. METHODS: Combined denaturing high-performance liquid chromatography (DHPLC) and multiple PCR techniques were used to detect the copy number of SMN1 gene. The carrier frequency was calculated. The spouse of the carrier was also screened, and prenatal diagnosis was provided to the couples who were both positive. RESULTS: Among the 4931 pregnant women, 61 were found to harbor only one copy of the SMN1 gene, which yielded a carrier rate of 1.2%. Subsequent testing has identified 1 fetus carrying homozygous deletions of the SMN1 gene. CONCLUSION: The carrier rate of SMA mutation in Liuzhou region is slightly lower than that of other regions of southern China. DHPLC can effectively screen the carriers of SMA mutation and provide a basis for genetic counseling and prenatal diagnosis.