The Z-Scheme MIL-88B(Fe)/BiOBr Heterojunction Promotes Fe(III)/Fe(II) Cycling and Photocatalytic-Fenton-Like Synergistically Enhances the Degradation of Ciprofloxacin.

The Z-scheme MIL-88B/BiOBr (referred to as MxBy, whereas x and y are the mass of MIL-88B(Fe) and BiOBr) heterojunction photocatalysts are successfully prepared by a facile ball milling method. By adding low concentration H2O2 under visible light irradiation, the Z-scheme heterojunction and photocatalytic-Fenton-like reaction synergistically enhance the degradation and mineralization of ciprofloxacin (CIP). Among them, M50B150 showed efficient photodegradation efficiency and excellent cycling stability, with 94.6% removal of CIP (10 mg L-1) by M50B150 (0.2 g L-1) under 90 min of visible light. In the MxBy heterojunctions, the rapid transfer of photo-generated electrons not only directly decomposed H2O2 to generate ·OH, but also improved the cycle of Fe3+/Fe2+ pairs, which facilitated the reaction with H2O2 to generate ·OH and ·O2 - radicals. In addition, the effects of photocatalyst dosages, pH of CIP solution, and coexisting substances on CIP removal are systematically investigated. It is found that the photocatalytic- Fenton-like reaction can be carried out at a pH close to neutral conditions. Finally, the charge transfer mechanism of the Z-scheme is verified by electron spin resonance (ESR) signals. The ecotoxicity of CIP degradation products is estimated by the T.E.S.T tool, indicating that the constructed photocatalysis-Fenton-like system is a green wastewater treatment technology.

The identification and classification of candidate genes during the zygotic genome activation in the mammals.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway.

Autism spectrum disorder (ASD) is a highly variable neurodevelopmental disorder that typically manifests childhood, characterized by a triad of symptoms: impaired social interaction, communication difficulties, and restricted interests with repetitive behaviors. De novo variants in related genes can cause ASD. We present the case of a 6-year-old Chinese boy with autistic behavior, including language communication impairments, intellectual disabilities, stunted development, and irritability in social interactions. Using Sanger sequencing, we confirmed a pathogenic in the RERE gene (NM_012102.4) (c.3732delC, p.Tyr1245Thrfs*12; EX21; Het). Subsequently, we generated an RERE point mutation cell line (ReMut) using CRISPR/Cas9 Targeted Genome Editing. Immunofluorescence was conducted to determine the location of the mutant RERE. RNA-sequencing and mass spectrometry analyses were performed to elucidate the ASD-related genes and signaling pathways disrupted by this variant in RERE. We identified 3790 differentially expressed genes and 684 differentially expressed proteins. The SHH signaling pathway was found to be downregulated, and the Hippo pathway was upregulated in ReMut. Genes implicated in autism, such as CNTNAP2, STX1A, FARP2, and GPC1, were significantly downregulated. Simultaneously, we noted alterations in HDAC1 and HDAC2, which are members of the WHHERE complex, suggesting their role in the pathogenesis of this patient. In conclusion, we report a de novo variant in RERE associated with autistic behavior. The finding that ASD is associated with RERE variants underscore the role of genetic factors in ASD and provides insights regarding the mechanisms underlying RERE variants in disease onset.

Development of Tailored Graphene Nanoparticles: Preparation, Sorting and Structure Assessment by Complementary Techniques.

We present a thorough structural characterization of Graphene Nano Particles (GNPs) prepared by means of physical procedures, i.e., ball milling and ultra-sonication of high-purity synthetic graphite. UV-vis absorption/extinction spectroscopy, Dynamic Light Scattering, Transmission Electron Microscopy, IR and Raman spectroscopies were performed. Particles with small size were obtained, with an average lateral size = 70−120 nm, formed by few = 1−10 stacked layers, and with a small number of carboxylic groups on the edges. GNPs relatively more functionalized were separated by centrifugation, which formed stable water dispersions without the need for any surfactant. A critical reading and unified interpretation of a wide set of spectroscopic data was provided, which demonstrated the potential of Specular Reflectance Infrared Spectroscopy for the diagnosis and quantification of chemical functionalization of GNPs. Raman parameters commonly adopted for the characterization of graphitic materials do not always follow a monotonic trend, e.g., with the particle size and shape, thus unveiling some limitations of the available spectroscopic metrics. This issue was overcome thanks to a comparative spectra analysis, including spectra deconvolution by means of curve fitting procedures, experiments on reference materials and the exploitation of complementary characterization techniques.

Checkerboard arranged G4 nanostructure-supported electrochemical platform and its application to unique bio-enzymes examination.

In this study, a checkerboard arranged G4 nanostructure-supported electrochemical platform is developed well for the application to unique bio-enzymes examination. Herein, we focus on the two bio-enzymes involving histone acetyltransferase (HAT) and terminal deoxynucleotidyl transferase (TdT); the former leads to the acetyl transfer of acetyl coenzyme A to the lysine residue of the substrate peptide and the latter achieves the polymeric extension of DNA without template under a unique pool of dATP and dGTP (4: 6). A complex of antibody and short DNA is introduced onto the electrode surface based on the affinity interaction between acetyl in acetylated peptide and its antibody. and used for initiating reaction. Then, TdT-yielded rich-G sequence is formed to act as the backbone of checkerboard, and subsequently free G-DNAs can be stacked continually on the backbone under Mg2+. An excellent electrocatalytic signal to H2O2 emerges noticeably, which is related with the activity of HAT p300 and TdT with a low detection limit of 2.3 pM and 0.38 mU/mL, respectively. Finally, this strategy is also used successfully for the inhibitor screening and complex sample analysis, which has important implications for the advancement of HAT- and TdT-related electrochemical bioassay and drug discovery.

Novel mutations in TUBB8 and ZP3 cause human oocyte maturation arrest and female infertility.

PURPOSE: Variations in many genes may lead to the occurrence of oocyte maturation defectsand female infertility. The objective was to describe newly discovered mutations in TUBB8 and ZP3, and to characterise the accompanying spectrum of phenotypes and modes of inheritance. METHODS: TUBB8 and ZP3 were sequenced from genomic DNA samples extracted from peripheral blood of patients and their family members by the whole-exome sequencing. The TUBB8 and ZP3 sequences are then aligned with cryptographic software to identify rare variations. Sanger sequencing and mass spectrometry were used to validate mutations. ExAC database was used to retrieve the frequency of corresponding mutations. PolyPhen-2 and PROVEAN were analyzed for mutations using silicon. RESULTS: We identified Three novel mutations and two known variant in TUBB8 and ZP3 associated with maturation in five families, and fertilization and developmental arrest are in these patients. These mutations include four heterozygous mutations in TUBB8 (c.730G > A, p.Gly244Ser, c.124C > G, p.Leu42Val, c.1172G > T, p.Arg391Leu and c.178G > A, p.Val60Met), and a heterozygous mutation in ZP3 (c.400G > A, p.Ala134Thr). Among them, these variants of TUBB8 were highly conserved among primates. CONCLUSION: As far as we know, the TUBB8 mutations detected in our study at four sites have not been reported before, and the variant of ZP3 has been published as pathogenic. Our findings extend the known mutant spectrum of TUBB8 and ZP3, and provide insights into the etiology of infertility in human women. The exact molecular mechanism has not been analyzed and should be further investigated in the future.

Development of ZnO nanoflowers-assisted DNAzyme-based electrochemical platform for invertase and glucose oxidase-dominated biosensing.

The investigation on invertase (INV) and glucose oxidase (GOx)-dominated biological process offers a new opportunity for the development of clinical diagnosis and prognostic treatment. Herein, a ZnO nanoflowers (ZnONFs)-assisted DNAzyme-based electrochemical platform for INV- and GOx-dominated biosensing is proposed by the change of pH in microenvironment. In this strategy, INV can usually catalyze the dissolution of sucrose to generate glucose, and glucose is then consumed by GOx to produce H2O2 and gluconic acid, in which ZnONFs can be effectively etched into free Zn2+ ions. Subsequently, the released Zn2+ ions have a shearing action for Zn2+-specific DNAzyme, thus triggering hybridization chain reaction along with the imbedding of methylene blue. The excellent electrochemical signals illustrate the method can be employed well for testing sucrose, INV and GOx with a low detection limit (0.019 µM, 0.047 mU/mL and 0.012 mU/mL, respectively). Finally, a series of basic and advanced logic gates (YES, AND, INHIBIT, and AND-AND-INHIBIT) in the biological process are constructed with different logic inputs, providing a valuable platform for the establishment of advanced molecular devices for bioanalysis and clinical diagnostics.

Supramolecular Host-Guest Interaction-Driven Electrochemical Recognition for Pyrophosphate and Alkaline Phosphatase Analysis.

We report an electrochemical biosensor based on the supramolecular host-guest recognition between cucurbit[7]uril (CB[7]) and L-phenylalanine-Cu(II) complex for pyrophosphate (PPi) and alkaline phosphatase (ALP) analysis. First, L-Phe-Cu(II) complex is simply synthesized by the complexation of Cu(II) (metal node) with L-Phe (bioorganic ligand), which can be immobilized onto CB[7] modified electrode via host-guest interaction of CB[7] and L-Phe. In this process, the signal of the complex-triggered electro-catalytic reduction of H2 O2 can be captured. Next, due to the strong chelation between PPi and Cu(II), a biosensing system of the model "PPi and Cu(II) premixing, then adding L-Phe" was designed and the platform was applied to PPi analysis by hampering the formation of L-Phe-Cu(II) complex. Along with ALP introduction, PPi can be hydrolyzed to orthophosphate (Pi), where abundant Cu(II) ions are released to form L-Phe-Cu(II) complex, which gives rise to the catalytic reaction of complex to H2 O2 reduction. The quantitative analysis of H2 O2 , PPi and ALP activity was achieved successfully and the detection of limits are 0.067 µM, 0.42 µM and 0.09 mU/mL (S/N=3), respectively. With its high sensitivity and selectivity, cost-effectiveness, and simplicity, our analytical system has great potential to for use in diagnosis and treatment of ALP-related diseases.

Effective Anti-Oxidation Repair Coating for C/C Brake Materials Comprising Lead-Borosilicate and Bismuth-Borosilicate Glass.

To achieve effective antioxidation of on-site repair coating for C/C brake materials in the full temperature range (500-900 °C), lead glass and bismuth glass were introduced into the borosilicate glass to acquire the protective coatings. Before preparing coating samples, the thermal gravity characteristics of the lead/bismuth-borosilicate glass powders were analyzed by TG/DSC. The results revealed that the temperature at which weight gain begins was 495 °C and 545 °C, respectively. The oxidation behaviors of the lead- and bismuth-modified borosilicate glass coatings were compared at 500 °C, and the antioxidation properties of the former were further examined from 500 to 900 °C. The oxidation results indicated that mixing lead glass with borosilicate glass realized effective oxidation resistance in the full temperature range. With a lead content of 20%, the lead-borosilicate glass coating was able to protect C/C substrates from oxidation. The corresponding weight loss of the lead-glass-coated samples was -1.89% when oxidized at 500 °C for 10 h, while the weight loss was -2.55% when further oxidized at 900 °C for 10 h. However, mixing bismuth glass with borosilicate glass was difficult to achieve the oxidation resistance of the coating at 500 °C due to the significant phase separation.

Multidisciplinary management for Peutz-Jeghers syndrome and prevention of vertical transmission to offspring using preimplantation genetic testing.

BACKGROUND: Peutz Jeghers syndrome (PJS) is an autosomal dominant genetic disorder caused by STK11 mutation with a predisposition to gastrointestinal polyposis and cancer. PJS patients suffer poor quality of life and are highly concerned about whether deleterious mutations transmit to their offspring. Therefore, this study aimed to propose feasible clinical management and provide effective preimplantation genetic testing for monogenic defect (PGT-M) strategies to protect offspring from inheriting the disease. METHODS: A hospital-based clinical retrospective analysis reviewing the clinical characteristics and fertility aspects was first conducted on 51 PJS patients at the First Affiliated Hospital of Zhengzhou University between January 2016 and March 2021. Among the 51 patients, the PGT-M strategy was further carried out in 4 couples, which started with a biopsy of the trophectoderm cells of embryos and whole genome amplification using multiple displacement amplification. Thereafter, single nucleotide polymorphism linkage analyses based on karyomapping were performed with copy number variations of the embryos identified simultaneously. Finally, prenatal diagnosis was used to verify the validity of the PGT-M results. RESULTS: A comprehensive management flowchart adopted by the multidisciplinary team model was formulated mainly focusing on clinical genetic and gastrointestinal aspects. Under the guidelines of this management, 32 embryos from 4 PJS pedigrees were diagnosed and 2 couples successfully conceived healthy babies free of the STK11 pathogenic mutation. CONCLUSIONS: Our comprehensive management could help affected families avoid having children with PJS through preimplantation genetic testing and provide meaningful guidance for multidisciplinary clinical practice on PJS.

Cascade i-motifs-dependent reversibleelectrochemical impedance strategy-oriented pH and terminal deoxynucleotidyl transferase biosensing.

In this study, we develop a novel and reversibleelectrochemical impedance strategy for pH and terminal deoxynucleotide transferase (TdT) analysis based on the TdT-assisted generation of long enough cytosine (C)-rich DNAs. The formation of this special DNA is rationally designed on 5'-thiol DNA modified Au electrode surface, and TdT can catalyze the extension of this 3'-OH end to form a long C-rich DNA in the presence of deoxycytidine triphosphate (dCTP). Here, we discover a reversible process, in which the TdT-generated C-rich DNA maintains an irregular single chain state under neutral conditions and some stable DNA i-motifs (cascade i-motifs) are formed due to the partial protonation of C under acidic conditions. More importantly, the electrochemical impedance spectroscopy (EIS) response varies with the configuration change of the TdT-mediated C-rich DNA under different pH conditions. In view of this, a unique EIS switch ("on-off-on") is constructed faithfully with the configuration change, thus achieving pH analysis well. Additionally, the TdT activity can be also detected well by recording the EIS response, because it can catalyze the DNA tailing process up to hundreds of cytosines; on the contrary, if its inhibitor exists, TdT-based extension and formation of cascade i-motifs will not occur. Using this strategy, the detection of limit for TdT is 0.79 × 10-5 U/mL (pH 7.0) and 0.25 × 10-5 U/mL (pH 5.8) (S/N = 3), respectively. All the above features make our biosensor a promising assay for in situ monitoring of pH and TdT in complex clinical diagnosis.

The single-nucleotide polymorphism rs743572 of CYP17A1 shows significant association with polycystic ovary syndrome: a meta-analysis.

Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving cytochrome P450, 17α-hydroxylase (CYP17A1). This meta-analysis aimed to evaluate the association between CYP17A1 polymorphism rs743572 and PCOS risk. Studies on the CYP17A1 gene were retrieved by searching PubMed, Embase and Web of Science and statistical analyses were performed by STATA software. Fifteen eligible studies were included, dated from January 1994 to 19 November 2020, involving 2277 patients with PCOS and 1913 control individuals. Overall, the results showed that the rs743572 T>C mutation was most likely to be associated with PCOS risk under the recessive model, which was further confirmed by heterogeneity analysis and publication bias detection (CC versus CT + TT, odds ratio [OR] 1.24, 95% confidence interval [CI] 1.02-1.50, P = 0.028, I²â€¯= 35.9%). Moreover, subgroup analysis by ethnicity demonstrated that Caucasian but not Asian women carrying the CC genotype of rs743572 had an elevated risk of PCOS (CC versus CT + TT, OR 1.45, 95% CI 1.03-2.06, P = 0.035, I²â€¯= 15.10%, six studies). In conclusion, rs743572 is highly likely to be a risk factor for PCOS, and the mutant genotype CC may increase susceptibility to PCOS in Caucasians rather than Asians.