Using the Photo-Piezoelectric Effect of AuPt@BaTiO3 Oxidase Mimetics for Colorimetric Detection of GSH in Serum.

Nanozymes possess major advantages in catalysis and biosensing compared with natural nanozymes. In this study, the AuPt@BaTiO3 bimetallic alloy Schottky junction is prepared to act as oxidase mimetics, and its photo-piezoelectric effect is investigated. The synergy between the photo-piezoelectric effect and the local surface plasmon resonance enhances the directional migration and separation of photogenerated electrons, as well as hot electrons induced by the AuPt bimetallic alloy. This synergy significantly improves the oxidase-like activity. A GSH colorimetric detection platform is developed based on this fading principle. Leveraging the photo-piezoelectric effect allows for highly sensitive detection with a low detection limit (0.225 µM) and reduces the detection time from 10 min to 3 min. The high recovery rate (ranging from 99.91% to 101.8%) in actual serum detection suggests promising potential for practical applications. The development of bimetallic alloy heterojunctions presents new opportunities for creating efficient nanozymes.

Using Multistage Energy Barrier of Heterojunctions in Improving Cr(VI) Detection.

Detecting heavy metals in seawater is challenging due to the high salinity and complex composition, which cause strong interference. To address this issue, we propose using a multistage energy barrier as an electrochemical driver to generate electrochemical responses that can resist interference. The Ni-based heterojunction foams with different types of barriers were fabricated to detect Cr(VI), and the effects of the energy barriers on the electrochemical response were studied. The single-stage barrier can effectively drive the electrochemical response, and the multistage barrier is even more powerful in improving sensing performance. A prototype Ni/NiO/CeO2/Au/PANI foam with multistage barriers achieved a high sensitivity and recovery rate (93.63-104.79%) in detecting seawater while resisting interference. The use of multistage barriers as a driver to resist electrochemical interference is a promising approach.

Novel pathogenic variants in the androgen receptor gene associated with androgen insensitivity syndrome identified through exome sequencing and in silico analysis.

Androgen insensitivity syndrome (AIS) is a common disorder/differences of sex development with a 46, XY karyotype, but diverse genital phenotypes. Various pathogenic variants within the androgen receptor (AR) gene on the X chromosome are the primary pathogenesis of AIS. However, some patients with AIS still lack a definitive molecular diagnosis. Here, molecular diagnosis of eight patients with the clinical phenotype of AIS was performed using exome sequencing. We found eight variants of the AR gene, including p.(C131*), p.(W435*), p.(T653Lfs*8), c.2318+1G>T, p.(S397R), p.(Y572C), p.(S648G), and p.(D691G), and a pathogenic copy number variation covering a deletion of exon 2 of AR gene. Patient pedigree validation confirmed that the discovered variants conformed to the X-linked recessive inheritance patterns of AIS. In silico analysis indicated that the splice site variant (c.2318+1G>T) could lead to loss of the original 5' splice donor site and exon skipping. Missense variants, including p.(S397R), p.(S648G), and p.(D691G), may affect the structure and function of the AR protein. Our results highlight the applicability of exome sequencing for molecular diagnosis of AIS. The novel variants found in this study enrich the pathogenic variant spectrum of the AR gene and provide a basis for the diagnosis and management of patients with AIS. A definite molecular diagnosis will provide accurate guidance for genetic counseling of proband's family members.

Plasmonic Array at the Liquid-Liquid Interface: A Dual-Mode Optical Sensing Platform for Multianalytes.

Analyte-triggered nanoparticle (NP) assemblies in bulk colloidal suspension have been extensively utilized in various optical sensors. Nevertheless, the assembling process is still limited by the slow diffusion dynamics of NPs and the low concentration of analytes in trace detections, which hinders further improvement of the sensitivity and repeatability of the sensors. In this work, by functionalizing the gold NPs with specific ligands, we constructed a dual-mode optical sensing platform for multianalytes based on the plasmonic NP array at the liquid-liquid interface. Through emulsification, the NP diffusion kinetics are boosted for several orders, and the NPs are condensed from the bulk aqueous phase to the liquid-liquid interface as a plasmonic array. The as-formed metasurface generates major reflectance and surface-enhanced Raman scattering changes in response to analytes, providing two optical sensing modes. As prototypes, cysteine and glucose are selected as the target molecules, achieving the limit of detection as 193 ± 2 and 297 ± 12 pM, respectively.

The construction and destruction of gold nanoparticle assembly at liquid-liquid interface for Cd2+ sensing.

The analyte-induced aggregation of plasmonic nanoparticles (NPs) in the bulk solution have been widely employed in optical sensors. However, in trace detection, the slow diffusion kinetics of NPs and the ultralow concentration of analytes significantly limit the binding opportunity of the analytes, thus impose penalties on the sensitivity, reproducibility and response time of the sensors. Herein, we propose a novel sensing method with two working modes that based on the construction/destruction of NP arrays at the liquid-liquid interface (LLI). For the turning-on mode, the emulsion state of the two immiscible liquid phases and specific binding between Cd2+ and cysteine (Cys) assemble NPs into a liquid plasmonic mirror at the LLI whose reflectance has a positive relationship with the concentration of Cd2+. For the turning-off mode, the assembled NP arrays are intentionally destructed with the introduction of Cd2+ which aggregates neighboring NPs, reduces the interfacial reflectance. Compared with the conventional bulk aggregation method in a single phase, the NPs here that scavenge Cd2+ in the aqueous phase are condensed onto the LLI, boosting the local NP concentration and the diffusion kinetics for several orders. The prototypes achieve the limit of detection as 29.3 ± 0.03 µg L-1, and are applicable in real-life samples.

Dual-Modulated Heterojunctions for Anti-Interference Sensing of Heavy Metals in Seawater.

Trace analyte detection in a complex environment such as in seawater is usually challenging for classic redox-based electrochemical sensors since the matrix effect of high salinity and various interfering species with similar redox properties can generate false positive/negative signals, thus impacting the sensitivity and specificity of the sensors. In this work, unlike redox-based approaches, we propose a novel sensing mode that relies on dual-modulated interfacial energy barriers of heterojunctions. By constructing the hierarchical structure of Ni/TiO2/porous-reduced graphene oxide/chitosan (CS), we introduce interfacial energy barriers of Schottky junctions into the electrochemical sensors for Cu2+. Most importantly, we found that two factors, light and the electrostatic interactions between the heterojunctions and Cu2+, can be coupled to regulate the height of the interfacial energy barrier and at last exponentially magnify the sensing signals in response to Cu2+. Since the electrostatic interaction is inert to redox, the proposed sensor is robust against most interfering species even in seawater. Illumination further enhances its sensitivity by 6.23 times and endows it a limit of detection of 0.22 nM. Such a dual-modulated sensing mode is also valid in other heterojunctions such as in the p-n junctions of Ni/NiO/MoS2/CS, demonstrating its potential in more universal applications.

Ion-bearing stairs: alkali metal complexes of 1,2-diaza-4-phospholides.

In this work, eight alkali metal complexes with 1,2-diaza-4-phospholide ligands were prepared and characterized by X-ray single-crystal structural analysis and NMR spectroscopy. Their structures showed varied coordination motifs: (i) a dimeric 1,2-diaza-4-phospholide lithium complex with exo-bidentate bridging coordination (4) consists of two lithium atoms that are linked via two µ2-bridging, κN,κN'-coordinated ligands; (ii) the polymeric chain 1,2-diaza-4-phospholide potassium complex (5) showed an ion-bearing stair-shaped chain structure running through axis a, where the steps are η2 interactions, and there is a transition platform between every two stairs; (iii) the polymeric chain 1,2-diaza-4-phospholide potassium complex (6) also presented a polymeric chain structure in the solid state but displayed a head-to-tail arrangement of two 1,2-diaza-4-phospholides; (iv) in comparison to 6, the 1,2-diaza-4-phospholide sodium complex (7) displayed a tetrameric structure, in which the sodium ions are arranged in a distorted tetrahedral fashion and each of them occupies a vertex of the tetrahedron; (v) the polymeric chain 1,2-diaza-4-phospholide potassium complex (8) presented a solvent-free chain structure, in which potassium ions each is η5-bonded by two 1,2-diaza-4-phospholides and η2-coordinated by another, consisting of a stair-shaped chain structure running through axis a but without significant intermolecular contacts between the adjacent stairs in comparison to that of 5; (vi) the polymeric chain 1,2-diaza-4-phospholide sodium complex (9) presented a solvent-free chain structure, in which sodium ions each is η1(N),η2(N,N),η1(P)-bonded by three 1,2-diaza-4-phospholides, consisting of a chain structure running through axis a; and (vii) the treatment complex 8 with elemental sulphur or selenium in the presence of crown ether gave rare thiophosphonato potassium [η3(S,P,S)-3,5-tBu2dp-(µ-K)(S2)([18]crown-6)] (10) or a selenophosphonato potassium [η3(Se,P,Se)-3,5-tBu2dp-(µ-K)(Se2)([18]crown-6)] (11). Both of the complexes crystallized in the orthorhombic space group Pnma as pale-yellow (or red) crystals. The X-ray diffraction analysis revealed 10 or 11 as a terminal complex with the η1,η1-X,X-coordination mode (X = S and Se). The 1H DOSY NMR spectroscopy study of the species 8 in DMSO-d6 suggested that polymeric complexes (4-9) in the solid state should dissociate into the related monomers in the solutions when the donor solvents were used.

Using photo-induced p-n junction interface effect of CoMn2O4/ß-MnO2 oxidase mimetics for colorimetric determination of hydroquinone in seawater.

Detection of pollutants in seawater faces a great challenge of strong interference, and the facile detection method is lacked. The CoMn2O4/ß-MnO2 p-n junction oxidase mimetics were successfully prepared for colorimetric detection of hydroquinone in seawater. The catalysis ability was enhanced significantly by the photo-induced p-n junction interface effect. It not only promoted the formation of H2O2 by suppressing the recombination of photon-generated carriers, but also provided the driving force for electron transport. The colorimetric detection of hydroquinone was achieved by fading and exhibited good adaptability in seawater. The obtained good recovery rate (97.23%-101.37%) in seawater makes it an inspiring method for practical application. The photo-induced p-n junction interface effect provides an opportunity for developing the application of colorimetric sensing in seawater detection.

Hypogonadotropic hypogonadism associated with another small supernumerary marker chromosome (sSMC) derived from chromosome 22, a case report.

The idiopathic hypogonadotropic hypogonadism (IHH) is portrayed as missing or fragmented pubescence, cryptorchidism, small penis, and infertility. Clinically it is characterized by the low level of sex steroids and gonadotropins, normal radiographic findings of the hypothalamic-pituitary areas, and normal baseline and reserve testing of the rest of the hypothalamic-pituitary axes. Delay puberty and infertility result from an abnormal pattern of episodic GnRH secretion. Mutation in a wide range of genes can clarify ~40% of the reasons for IHH, with the majority remaining hereditarily uncharacterized. New and innovative molecular tools enhance our understanding of the molecular controls underlying pubertal development. In this report, we aim to present a 26-year-old male of IHH associated with a small supernumerary marker chromosome (sSMC) that originated from chromosome 22. The G-banding analysis revealed a karyotype of 47,XY,+mar. High-throughput DNA sequencing identified an 8.54 Mb duplication of 22q11.1-q11.23 encompassing all the region of 22q11 duplication syndrome. Pedigree analysis showed that his mother has carried a balanced reciprocal translocation between Chromosomes 22 and X[t(X;22)]. To the best of our knowledge, this is the second confirmed case of IHH with an sSMC deriving from chromosome 22. Based on our study, the duplicated chromosome fragment 22q11.1-q11.23 might be the reason for the phenotype of our case. Meanwhile, High-throughput DNA sequencing combined with cytogenetic analysis can provide a more accurate clinical diagnosis for patients carrying sSMCs.

Fabrication of the Ni-based composite wires for electrochemical detection of copper(â ¡) ions.

Copper ions (Cu2+) pollution in the water environment poses a great threat to the health function of life-sustaining metabolic activities. However, the current detection methods need relatively expensive instruments, complex operation procedures and long time, so a facile and direct detection method is desired to be developed. In this work, the Ni-based composite wires with p-n junction (the Ni/NiO/ZnO/Chitosan wire) and Schottky junction (the Ni/NiO/Au/Chitosan wire) were fabricated, and the barrier driven electrochemical sensing mechanism was studied. The direct and facile detection of Cu2+ was achieved with a wide linear range (0-6000 nM) and a low LOD (0.81 nM). The excellent stability and recovery in real water samples made the Ni-based composite wires a promising candidate for the practical application. The interfacial barriers of semiconductor can be used as a special sensing factor to develop novel sensors.

Construction of hierarchical 2D/2D Ti3C2/MoS2 nanocomposites for high-efficiency solar steam generation.

Solar steam generation has been considered one of the most promising approaches for dealing with the energy and freshwater resource crises in recent years. However, achieving high efficiency in photo-thermal conversion remains a considerable challenge. Here, a series of hierarchical Ti3C2/MoS2 nanocomposites were designed for steam generation by a hydrothermal method. When the mass fraction of MoS2 reached 65 wt% (TM-3), the Ti3C2/MoS2 nanocomposite presented a strong broad-band light absorption of 92.4% from the UV to NIR region because of the accordion-like layered structure. The evaporation rate and solar-thermal conversion efficiency of the TM-3 with as-fabricated evaporator could reach 1.36 kg·m-2·h-1 and 87.2% under 1 kW/m2, due to the excellent light absorption ability of TM-3 and the low thermal energy loss (8.8%) of the evaporator. Meanwhile, TM-3 permits the evaporator to have remarkable cycle stability because of its hydrophobic properties. Moreover, TM-3 showed excellent seawater desalination and wastewater treatment abilities. Thus, the excellent light absorption ability, photo-thermal conversion efficiency, and stability of the overall system suggested that these nanocomposites show great potential applications in synergetic solar desalination and sewage treatment.

1,2,4-Triazolato paddlewheel dibismuth complexes with very short Bi(II)-Bi(II) bonds: bismuth(III) oxidation of 1,2,4-triazolato anions into neutral N-1,2,4-triazolyl radicals.

Bismuth(iii) oxidation of 3,5-di-substituted-1,2,4-triazolato anions afforded a paddlewheel 1,2,4-triazolato dibismuth complex [L2(Bi-Bi)L2] (L = η1,η1-3,5-R2tz, R = Ph (3), iPr (4)) with very short Bi(ii)-Bi(ii) bonds (2.8650(4)-2.8721(3) Å). The reaction involved the intermediates of the organobismuth radical [Bi(R2tz)2]˙ and neutral N-1,2,4-triazolyl radical [3,5-R2tz]˙. The dimerization of the former produced the corresponding dibismuth complex while the latter was trapped by using spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) to give the radical adduct of {(3,5-R2tz)(DMPO)}˙ which was unambiguously evidenced by EPR analysis.

Preparation of NiMn2O4/C necklace-like microspheres as oxidase mimetic for colorimetric determination of ascorbic acid.

The NiMn2O4/C necklace-like microspheres (NLM) were successfully prepared by hydrothermal method and oil bath. This unique necklace-like structure makes them exhibit the enhanced intrinsic oxidase-like activity, as the special interface can help capture electrons from 3,3',5,5'-tetramethylbenzidine. The fabricated NiMn2O4/C NLM were successfully used as the high-performance oxidase mimetic to catalyze the oxidation of TMB directly for the color reaction. A simple colorimetric method for detection of ascorbic acid by fading was developed, and the high sensitivity with the low detection limit (0.047 µM) was achieved. It is a facile route to fabricate the NiMn2O4/C NLM as the high-performance oxidase mimetic for colorimetric biosensing.

Using the interfacial barrier effects of p-n junction on electrochemistry for detection of phosphate.

A novel type of electrochemical sensor for detection of phosphate in water environment was developed by combining the interfacial barrier of p-n junction with the adsorption of phosphate. The electrochemical response was produced by the induced change of the barrier height, which was only caused by the specific adsorption of phosphate. Two linear concentration ranges (0-0.045 mg L-1 and 0.045-0.090 mg L-1) with two sensitivities (4.98 µA (µg L-1)-1 and 1.28 µA (µg L-1)-1) were found. The good performance made the sensor meet the requirements of the World Health Organization for drinking water (1 mg L-1 of phosphate). It is an approach to develop electrochemical sensors by employing the interfacial barrier effects on electrochemistry.

Trifluridine selectively inhibits cell growth and induces cell apoptosis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with a high rate of recurrence and metastasis. Trifluridine (TFT) is a thymidine analog to target thymidylate synthase (TS) and has potent ant-herpes simplex virus activity. However, little is known whether and how TFT treatment can modulate the growth of TNBC. In this study, we found that treatment with TFT selectively inhibited the proliferation of TNBC cells and triggered their apoptosis. TFT treatment significantly up-regulatd the expression of G1 phase inhibitor p21 and p27, and pro-apoptotic factor γ-H2AX, Bax and cleaved caspase-7 in TNBC cells. TFT treatment significantly down-regulated the expression of proliferating cell nuclear antigen (PCNA), minichromosome maintenance component 7 (MCM7) and anti-apoptotic Bcl-2 in TNBC cells. TFT treatment significantly mitigated the growth of implanted mouse TNBC in vivo, associated with increased expression of γ-H2AX and cleaved caspase-7 in mouse TNBC tumors. TS expression was up-regulated in breast cancer, particularly in TNBC tissues, and up-regulated TS expression was significantly associated with a shorter overall survival and disease free survival in TNBC patients. TS silencing selectively decreased the proliferation of TNBC cells, but did not trigger their apoptosis. Treatment with TFT induced DNA double strand break (DSB) and damages in TNBC cells. Collectively, TFT selectively inhibited the growth of TNBC by inducing chromosome instability and inhibiting thymidine synthase. Therefore, TFT may be valuable for the intervention of TNBC.

Fabrication of the Ni/ZnO/BiOI foam for the improved electrochemical biosensing performance to glucose.

The Ni foam decorated with ZnO/BiOI core-shell p-n junction nanorods was prepared and employed as an enzyme loading matrix to detect glucose. The detection potential was decreased significantly (0.3 V) and the sensitivity was enhanced largely (115.2 µA mM-1 cm-2). The metal-semiconductor foam can afford the porous surface for loading enzymes and achieving the multiple catalysis. More important, the built-in electric field and electron well in the p-n junction interface provide the driving force for electron transport. It was an effective strategy to enhance the biosensing performance by the rational design of p-n junction.

Regioselective N-Addition/Substitution Reaction of α-Alkylidene Pyrazolinones with Propargyl Sulfonium Salts to Construct Allylthio-Containing Pyrazolones.

The regioselective N-addition/substitution reaction between α-alkylidene pyrazolinones and propargyl sulfonium salts has been developed to construct functionalized allylthio-containing pyrazolones with moderate to excellent yields. α-Alkylidene pyrazolinones act as N-nucleophilic agents which are distinguished from reported C-nucleophilic reactions. Excellent regioselectivity, readily available starting materials, the broad range of substrates, gram-scale synthesis, and simple operation illustrate the synthetic advantages of this new reaction pathway.

Fabrication of CQDs/MoS2/Mo foil for the improved electrochemical detection.

We proposed a new method for regulating the electrochemical signal by using Schottky barrier. The results show that the height of Schottky barrier can be altered by adsorbing charged substance to control the enhancement and attenuation of electrochemical signal. The Schottky interface formed by MoS2 and CQDs (carbon quantum dots) can achieve the selective detection of dopamine and overcome the distraction of ascorbic acid and uric acid with similar redox signal. The combination of Schottky barrier and electrochemical detection enhance the sensitivity and selectivity of electrochemical sensor significantly. It is a new strategy for improving electrochemical detection by introducing Schottky barrier into electrochemical process.

Novel pathogenic mutations in disorders of sex development associated genes cause 46,XY complete gonadal dysgenesis.

Disorders of sex development (DSDs) are congenital conditions in which chromosomal, gonadal and sex is atypical. It is difficult to diagnose and manage patients with DSD in clinical practice, and the molecular etiology of DSD is still not completely understood. Here, we identified two novel pathogenic mutations from three unrelated Chinese patients with 46,XY complete gonadal dysgenesis (CGD) that is a clinical subgroup of DSD by whole exome sequencing. A novel mutation in the SRY gene (c.161delG) was identified in the first patient, and the second patient carried a novel missense mutation in the MAP3K1 gene (c.2117T>G). Bioinformatics analysis found that the deletion of SRY (c.161delG) led to a premature stop codon at amino acid 59 in the SRY protein, which resulted in lacking the DNA binding domain of SRY protein. Functional studies found that the missense mutation in the MAP3K1 gene (c.2117T>G) could interfere with the gene function through increasing the phosphorylation of the downstream targets of MAP3K1, ERK1/2 and p38, which resulted in reducing testis-determining factor SOX9 expression and increasing ovary-promoting factor ß-catenin activity. According to the American college of medical genetics and genomics (ACMG) standards and guidelines, these mutations were categorized as "pathogenic" mutations. Thus, our findings provide two novel pathogenic mutations associated with 46,XY CGD that can improve the etiological diagnosis for 46,XY CGD. ABBREVIATIONS.

Auxetic Thermoresponsive Nanoplasmonic Optical Switch.

Development and use of metamaterials have been gaining prominence in large part due to the possibility of creating platforms with "disruptive" and unique optical properties. However, to date, the majority of such systems produced using micro or nanotechnology are static and can only perform certain target functions. Next-generation multifunctional smart optical metamaterials are expected to have tunable elements with the possibility of controlling the optical properties in real time via variation in parameters such as pressure, mechanical stress, and voltage or through nonlinear optical effects. Here, we address this challenge by developing a thermally controlled optical switch, based on the self-assembly of poly( N-isopropylacrylamide)-functionalized gold nanoparticles on a planar macroscale gold substrate. We show that such meta-surfaces can be tuned to exhibit substantial changes in the optical properties in terms of both wavelength and intensity, through the temperature-controlled variation of the interparticle distance within the nanoparticle monolayer as well as its separation from the substrate. This change is based on temperature-induced auxetic expansion and contraction of the functional ligands. Such a system has potential for numerous applications, ranging from thermal sensors to regulated light harnessing.