One-Step Formation of Pickering Double Emulsion Costabilized by Hydrophobic Silica Nanoparticles and Sodium Alginate.

Pickering double emulsions exhibit higher stability and biocompatibility compared with surfactant-stabilized double emulsions. However, tailored synthesis of particle stabilizers with appropriate wettability is time consuming and complicated and usually limits their large-scale adoption. Using binary stabilizers may be a simple and scalable strategy for Pickering double emulsion formation. Herein, commercially available hydrophobic silica nanoparticles (SNPs) and sodium alginate (SA) as binary stabilizers are used to prepare O/W/O Pickering double emulsions in one-step emulsification. The influence of system composition on double emulsion preparation is identified by optical microscopy, confocal laser scanning microscopy, and interfacial tension and water contact angle analyses. The formation of the O/W/O Pickering double emulsion depends critically on the aqueous phase viscosity and occurrence of emulsion inversion. Both hydrophobic SNPs and SA adsorb at the droplet surface to provide a steric barrier, while SA also reduces interfacial tension and increases aqueous phase viscosity, giving double emulsion long-term stability. Their microstructure and stability are controlled by adjusting the SA concentration, water-oil volume ratio, concentration and wettability of the particle stabilizer, and oil type. As a demonstration, the middle layer of the as-prepared O/W/O Pickering double emulsions can be cross-linked in situ with calcium ions to produce calcium alginate porous microspheres. We believe that our strategy for double emulsion formation holds great potential for practical applications in food, cosmetics, or pharmaceuticals.

Dual-responsive colloidosome-like microgels as the building blocks for phase inversion of Pickering emulsions.

The intelligent regulation of microgel-stabilized Pickering emulsions with multi-responsiveness is presently constrained to the processes of emulsification and destabilization. However, the expansion of multi-control over Pickering emulsions to involve phase inversion and the investigation of the accompanying processes and mechanisms present a great challenge. In this study, a microgel with dual responsiveness to both pH and temperature was synthesized using an emulsion template. The resulting microgel exhibited a robust colloidosome-like structure, distinguished by the presence of monolayer-adsorbed silica nanoparticles. The regulation of the packing of surface-covered silica nanoparticles was easily achieved through the swelling of the microgel matrix. Furthermore, the wettability of the microgel can be adjusted between hydrophilic and hydrophobic intervals, allowing for the effective and dual-responsive phase inversion of Pickering emulsions. Moreover, it has been observed that colloidosome-like microgels can lead to unique interfacial structures during the emulsification process, thereby elucidating the fundamental mechanism governing emulsion phase inversion.

Multifunctional Silica-Modified Hybrid Microgels Templated from Inverse Pickering Emulsions.

Microgels are regarded as soft colloids with environmental responsiveness. However, the majority of reported microgels are inherently hydrophilic, resulting in aqueous dispersions, and only used in water-based applications. Herein, we reported an efficient method for hybridization of poly(N-isopropylacrylamide) microgel by coating hydrophobic silica nanoparticles on their surface. The resultant hybrid microgel had switchable surface wettability and could be dispersed in both aqueous and oil phases. Meanwhile, the coated hydrophobic silica nanoparticles solved the difficulty in redispersing microgels caused by particle aggregation and film formation during the drying process, providing a significant advantage in dried storage. Furthermore, the introduction of hydrophobic silica nanoparticles endowed the hybrid microgel with a variety of applications, including cargo encapsulation, active release induced by emulsion reversion, and trace water absorption.

Water-in-Oil Pickering Emulsions Stabilized by Hydrophobized Protein Microspheres.

Water-in-oil (w/o) Pickering emulsions have gained considerable attention in colloid science and daily applications. However, for the formation of w/o emulsions, especially those with high internal water content, the particulate stabilizers are required to be sufficiently hydrophobic, and synthetic or chemically modified particles have been mostly reported until now, which are not biocompatible and sustainable. We present a zein protein-based microsphere derived from the Pickering emulsion template, in which protein microspheres are feasibly in situ hydrophobized by silica nanoparticles, enabling the stabilization of w/o Pickering emulsions. The effects of microsphere concentration, water/oil volume ratio, oil types, and pH on the stabilization of prepared w/o emulsions are systematically studied, revealing prominent characteristics of the controllable size, high water fraction, universal adaptation of oils, as well as broad pH stability. As a demonstration, the Pickering emulsion effectively encapsulates vitamin C and shows high stability for long storage duration against ultraviolet radiation/heat. Therefore, this novel proteinaceous particle-stabilized w/o Pickering emulsion has great potential in the delivery and protection of water-soluble bioactive substrates.

The activation loop and substrate-binding cleft of glutaminase C are allosterically coupled.

The glutaminase C (GAC) isoform of mitochondrial glutaminase is overexpressed in many cancer cells and therefore represents a potential therapeutic target. Understanding the regulation of GAC activity has been guided by the development of spectroscopic approaches that measure glutaminase activity in real time. Previously, we engineered a GAC protein (GAC(F327W)) in which a tryptophan residue is substituted for phenylalanine in an activation loop to explore the role of this loop in enzyme activity. We showed that the fluorescence emission of Trp-327 is enhanced in response to activator binding, but quenched by inhibitors of the BPTES class that bind to the GAC tetramer and contact the activation loop, thereby constraining it in an inactive conformation. In the present work, we took advantage of a tryptophan substitution at position 471, proximal to the GAC catalytic site, to examine the conformational coupling between the activation loop and the substrate-binding cleft, separated by ∼16 Å. Comparison of glutamine binding in the presence or absence of the BPTES analog CB-839 revealed a reciprocal relationship between the constraints imposed on the activation loop position and the affinity of GAC for substrate. Binding of the inhibitor weakened the affinity of GAC for glutamine, whereas activating anions such as Pi increased this affinity. These results indicate that the conformations of the activation loop and the substrate-binding cleft in GAC are allosterically coupled and that this coupling determines substrate affinity and enzymatic activity and explains the activities of CB-839, which is currently in clinical trials.

Pickering Emulsions Simultaneously Stabilized by Starch Nanocrystals and Zein Nanoparticles: Fabrication, Characterization, and Application.

Using two types of colloidal particles having natural origins to synergistically stabilize Pickering emulsions is essential for food, cosmetics, and pharmaceutics, especially when neither particle can stabilize the Pickering emulsions alone. The use of two natural stabilizers avoids the complicated surface treatments of particles and the introduction of poisonous or harmful chemicals. In this work, we report an all-natural Pickering emulsion stabilized synergistically by starch nanocrystals and zein protein nanoparticles. Our result shows that the electrostatic interaction between the two types of particles greatly affects their assembled structure at the oil/water interface, which is closely related to the emulsion stability. Specifically, particle bilayers could form with oppositely charged particles at the interface to endow the emulsion with improved stability. As a demonstration, the resultant Pickering emulsions effectively carry ß-carotene and have high stability against high temperatures and ultraviolet radiation. This type of all-natural Pickering emulsion is a promising tool to protect and deliver liposoluble bioactive components.

Flexible and highly responsive photodetectors based on heterostructures of MoS2and all-carbon transistors.

Heterostructures of graphene and transition-metal dichalcogenides (TMDCs) are promising candidates for high-performance flexible photodetectors because of their high photoresponsivity and detectivity. However, the mechanical stability of current flexible photodetectors is limited, due to a mechanical mismatch between their two-dimensional channel materials and metallic contacts. Herein, we develop a type of mechanically stable, highly responsive, and flexible photodetector by integrating MoS2and all-carbon transistors. By combining the high mobility of graphene with the strong light-matter interactions of MoS2, our heterostructure photodetector exhibits a greatly improved photoresponse performance, compared with individual graphene or MoS2photodetectors. In addition, the mechanical properties of the all-carbon electrodes are a good match for those of the active two-dimensional channels, resulting in greatly improved electrical stability of the heterostructure photodetector under mechanical deformation. These capabilities make our heterostructure photodetector a promising candidate for flexible photodetection and photoimaging applications.

A Smart Route for Encapsulating Pd Nanoparticles into a ZIF-8 Hollow Microsphere and Their Superior Catalytic Properties.

The encapsulation of catalytically active noble metal nanoparticles (NM NPs) into metal-organic frameworks (MOFs) represents an effective strategy for enhancing their catalytic performance. Despite a myriad of reports on the nanocomposites consisting of NM NPs and MOFs, it remains challenging to develop a sustainable and convenient method for realizing confined integration of NM NPs within a porous and hollow zinc-based MOF. Herein, a simple and well-designed approach is reported to the fabrication of Pd@ZIF-8 hollow microspheres with a number of Pd nanoparticles immobilized on the inner surface. This method capitalized on the use of polyvinylpyrrolidone (PVP)-stabilized polystyrene (PS) microspheres as templates, to harness the dual functions of PVP for reducing PdCl2 to generate Pd NPs and coordinating with zinc ions to grow ZIF-8 shells. Consequently, it avoids the complicated protocols involving surface treatment of template microspheres that conventionally adopts hazardous or costly agents. The obtained Pd@ZIF-8 hollow microspheres exhibit outstanding catalytic activity, size selectivity, and stability in the hydrogenation of alkenes. This study presents both the advances in the green synthesis and great potential of Pd@ZIF-8 hollow microspheres for catalytic applications.

Carbon nanotube spiderweb promoted growth of hierarchical transition metal dichalcogenide nanostructures for seamless devices.

Hierarchical transition metal dichalcogenide (h-TMDC) nanostructures with abundant active edge sites and good electrical conductivity hold great promise for numerous applications. Here, we report a general method for the chemical synthesis of a series of large-area, free-standing h-TMDC films and their devices by using carbon nanotube (CNT) spiderwebs as both growth promoters and electrical/mechanical reinforcement networks. Our approach allows the seamless integration of h-TMDC nanostructures with abundant active edge sites and CNT networks with good electrical conductivity and mechanical flexibility. As a proof of concept, h-MoSe2/CNT hybrid films with CNT contacts have been chemically synthesized and applied as flexible electrocatalytic devices for hydrogen evolution reaction (HER). Owing to the seamless connection between the CNT contacts and the electroactive h-TMDC/CNT nanostructures, the flexible electrocatalytic devices exhibited excellent mechanical stability and maintained stable electrocatalytic performance under cyclic bendings. Our method can be readily extended to the large-scale production of various h-TMDC/CNT hybrid films and their seamless devices.

Measurements of Particle-Surface Interactions in Both Equilibrium and Nonequilibrium Systems.

Total internal reflection microscopy (TIRM) is a passive technique that measures colloidal interactions in aqueous solution. A traditional Boltzmann method requires that particles must fluctuate around equilibrium positions for a long time. A method based on multiparticle tracking and drift velocity method was developed to measure interactions in both equilibrium and nonequilibrium systems. This method relaxed the limitation of the traditional Boltzmann method and do not require any external force like optical tweezer. Theoretical predictions of particle sedimentation under the influence of various forces were investigated to determine the proper particle size and solution properties. We found that the polystyrene (PS) particle with a size of 2.1 µm took the longest time to finish sedimentation, and 5% (w/w) sucrose was chosen to suppress the Brownian motion. For single and ensemble particles in equilibrium, the experimental diffusion coefficients and potential energy profiles were consistent with the theoretical prediction. In nonequilibrium experiments, the van der Waals force between the bare/hybrid particles and flat surface was measured, and the silica shell acted to strengthen the van der Waals attraction. This method extends the application of TIRM to nonequilibrium systems without any active control. Moreover, the silica-coated PS core-shell hybrid particles facilitate surface modification with a variety of active chemicals. It would be a great advantage to measure all kinds of long-range interactions between surface-modified particles and surface in aqueous solution with TIRM.

Mechanism by which a recently discovered allosteric inhibitor blocks glutamine metabolism in transformed cells.

The mitochondrial enzyme glutaminase C (GAC) catalyzes the hydrolysis of glutamine to glutamate plus ammonia, a key step in the metabolism of glutamine by cancer cells. Recently, we discovered a class of allosteric inhibitors of GAC that inhibit cancer cell growth without affecting their normal cellular counterparts, with the lead compound being the bromo-benzophenanthridinone 968. Here, we take advantage of mouse embryonic fibroblasts transformed by oncogenic Dbl, which hyperactivates Rho GTPases, together with (13)C-labeled glutamine and stable-isotope tracing methods, to establish that 968 selectively blocks the enhancement in glutaminolysis necessary for satisfying the glutamine addiction of cancer cells. We then determine how 968 inhibits the catalytic activity of GAC. First, we developed a FRET assay to examine the effects of 968 on the ability of GAC to undergo the dimer-to-tetramer transition necessary for enzyme activation. We next demonstrate how the fluorescence of a reporter group attached to GAC provides a direct read-out of the binding of 968 and related compounds to the enzyme. By combining these fluorescence assays with newly developed GAC mutants trapped in either the monomeric or dimeric state, we show that 968 has the highest affinity for monomeric GAC and that the dose-dependent binding of 968 to GAC monomers directly matches its dose-dependent inhibition of enzyme activity and cellular transformation. Together, these findings highlight the requirement of tetramer formation as the mechanism of GAC activation and shed new light on how a distinct class of allosteric GAC inhibitors impacts the metabolic program of transformed cells.

[Genetic analysis of a 46,XY female with sex reversal due to duplication of NR0B1 gene].

OBJECTIVE: To explore the pathogenesis of a 46,XY female with sex reversal. METHODS: Peripheral blood lymphocytes of the patient were subjected to G-banding karyotype analysis. Sex chromosomes were analyzed with fluorescence in situ hybridization (FISH). SRY gene was analyzed by Sanger sequencing. The whole exome of the patient was subjected to next generation sequencing. Copy number variations (CNVs) of the NR0B1, SF1, SRY, SOX9 and WNT4 genes were validated by multiplex ligation-dependent probe amplification (MLPA). RESULTS: The patient had a 46,XY karyotype. FISH analysis showed that her sex chromosomes were X and Y. No mutation was found in the SRY gene, and no pathogenic mutation was detected in her exome. However, a duplication spanning approximately 67.31 kb encompassing the MAGEB1, MAGEB3, MAGEB4 and NR0B1 genes at Xp21, was predicted by software analysis. MLPA confirmed duplication of the NR0B1 gene in the patient and her mother. CONCLUSION: A duplication fragment of Xp21 encompassing the NR0B1 gene in the 46,XY female with sex reversal is transmitted from her asymptomatic carrier mother. Attention should be paid towards the insidious nature and high morbidity of this duplication.

[Application of quantitative fluorescencet-PCR in the prenatal diagnosis of chromosomale aneuploidies].

OBJECTIVE: To assess the accuracy of quantitative fluorescence PCR(QF-PCR) for the detection of fetal chromosomal aneuploidies and its values for prenatal diagnosis. METHODS: QF-PCR and chromosomal karyotyping were used to analyze 6066 amniotic fluid samples derived from 6034 pregnant women. RESULTS: Both QF-PCR and karyotyping analysis have detected 135 cases of fetal aneuploidies involving chromosomes 21, 18, 13, X, and Y. The QF-PCR assay was also successful in 67 cases for which amniotic fluid culture has failed. Furthermore, it has identified maternal cell contamination in 7 cases. By determining the consistency of short tandem repeat (STR) sites, the QF-PCR assay has identified 22 dizygotic twins among 32 twins with double chorions and double amniotic sacs. In 12 cases, it has signaled numerical chromosomal aberration by critical or partial abnormal values for the fluorescence peak area ratio, which were verified by karyotyping analysis as mosaicisms of chromosome aneuploidies. CONCLUSION: The QF-PCR can provide an useful supplement for chromosomal karyotyping and has an important role in rapid prenatal diagnosis.

All-Silica Submicrometer Colloidosomes for Cargo Protection and Tunable Release.

Colloidosomes have received considerable attention for the controlled delivery of active ingredients in medicine, agrochemicals, and cosmetics. However, most reported colloidosomes are highly permeable and size is larger than 1 µm. All silica colloidosomes have now been prepared with adjustable size, compact shell and low permeability. Our approach is based on the formation of inverse water-in-oil (w/o) emulsions stabilized solely by hydrophobic silica nanoparticles and subsequent locking of the particle at the oil-water interface by a simple sol-gel reaction of silica precursor at room temperature. The colloidosomes obtained display a robust and closed shell, ensuring a long-term retention of small hydrophilic molecules such as Methylene Blue. Remarkably, unlike all other reported silica colloidosomes, a timely and stepwise release of the encapsulated cargo can be triggered by adding ethanol or surfactant without destroying the capsule shell.

Mechanistic Basis of Glutaminase Activation: A KEY ENZYME THAT PROMOTES GLUTAMINE METABOLISM IN CANCER CELLS.

Glutamine-derived carbon becomes available for anabolic biosynthesis in cancer cells via the hydrolysis of glutamine to glutamate, as catalyzed by GAC, a splice variant of kidney-type glutaminase (GLS). Thus, there is significant interest in understanding the regulation of GAC activity, with the suggestion being that higher order oligomerization is required for its activation. We used x-ray crystallography, together with site-directed mutagenesis, to determine the minimal enzymatic unit capable of robust catalytic activity. Mutagenesis of the helical interface between the two pairs of dimers comprising a GAC tetramer yielded a non-active, GAC dimer whose x-ray structure displays a stationary loop ("activation loop") essential for coupling the binding of allosteric activators like inorganic phosphate to catalytic activity. Further mutagenesis that removed constraints on the activation loop yielded a constitutively active dimer, providing clues regarding how the activation loop communicates with the active site, as well as with a peptide segment that serves as a "lid" to close off the active site following substrate binding. Our studies show that the formation of large GAC oligomers is not a pre-requisite for full enzymatic activity. They also offer a mechanism by which the binding of activators like inorganic phosphate enables the activation loop to communicate with the active site to ensure maximal rates of catalysis, and promotes the opening of the lid to achieve optimal product release. Moreover, these findings provide new insights into how other regulatory events might induce GAC activation within cancer cells.

In Situ Growth of Clean Pd Nanoparticles on Polystyrene Microspheres Assisted by Functional Reduced Graphene Oxide and Their Excellent Catalytic Properties.

Herein an in situ growth of clean palladium nanoparticles (Pd NPs) on functional reduced graphene oxide (RGO)-coated polystyrene (PS) microspheres is achieved by a simple two-step process. On the basis of the hydrophobic interaction and π-electron interaction, the PS/RGO composite particles are first prepared by the reduction of graphene oxide in the presence of PS microspheres. Second, without using any additional reducing agent or stabilizer, the clean Pd NPs grow in situ on the surface of PS/RGO composite particles in water through a spontaneous redox reaction between Pd2+ and RGO. Significantly, owing to the stabilizer-free surface of Pd NPs and the synergistic effect of RGO and Pd NPs, the resultant PS/RGO@Pd composite particles feature pronounced catalytic activity toward the reduction of p-nitrophenol and Suzuki coupling reactions. Moreover, the catalyst particles can be easily recovered by centrifugation because of the large size of support microspheres and recycled consecutively.

A Hexagonal Covalent Porphyrin Framework as an Efficient Support for Gold Nanoparticles toward Catalytic Reduction of 4-Nitrophenol.

A hexagonal porphyrin-based porous organic polymer, namely, CPF-1, was constructed by 3+2 ketoenamine condensation of the C2 -symmetric porphyrin diamine 5,15-bis(4-aminophenyl)-10,20-diphenylporphyrin and 1,3,5-triformylphloroglucinol. This material exhibits permanent porosity and excellent thermal and chemical stability. CPF-1 can be employed as a superior supporting substrate to immobilize Au nanoparticles (NPs) as a result of the strong interactions between Au NPs and the CPF support. An Au@CPF-1 hybrid was synthesized by an interfacial solution infiltration method with NaBH4 as reducing agent. Au NPs (5 nm) grew on CPF-1 and were distributed without aggregation. Moreover, Au@CPF-1 exhibits superior catalytic activity compared to many other reported Au-based catalysts for the reduction of 4-nitrophenol in the presence of NaBH4 . In addition, Au@CPF-1 has excellent stability and recyclability, and it can be reused for three successive reaction cycles without loss of activity. The dense distribution of phenyl rings on the channel walls of the CPF support can reasonably be regarded as the active sites that adsorb the 4-nitrophenol molecule through hydrogen-bonding and C-H⋅⋅⋅π interactions, as was confirmed by the X-ray structure of model compound DAPP-Benz.

[Influence of sperm nucleoprotein transition on in vitro embryo development].

OBJECTIVE: To correlate sperm nucleoprotein transition (SNT) with sperm morphology, DNA damage and embryo development, and assess its value for assisted reproductive technology (ART). METHODS: The SNT of 437 infertile men underwent ART were assayed, and its correlation with sperm morphology, DNA damage, fertilization rate, normal fertilization rate, cleavage rate, available embryo rate, D3 high quality embryo rate, blastocyst formation rate and high quality blastocyst rate were analyzed. RESULTS: The normal morphology rate of sperms, DNA damage, fertilization rate, normal fertilization rate, cleavage rate, embryo transfer rate (ETR), D3 high quality embryo rate, blastocyst formation rate (BFR) and high quality blastocyst in normal males (Group A, abnormal rate≤30%, 135 subjects) did not significantly differ from those with an abnormal rate between 30% and 60% (Group B, 170 subjects) (P>0.05). For those with an abnormal rate of above 60% (Group C, 132 subjects), the sperm normal morphology rate, DNA damage, normal fertilization rate, ETR, D3 high quality embryo rate, high quality blastocyst rate were significantly lower compared with Group A (P<0.01), while no significant difference was found in fertilization rate, cleavage rate and BFR between groups A and C (P>0.05). CONCLUSION: SNT is related with sperm morphology rate, DNA damage and embryo development, and should be assessed before ART.

[Analysis of genetics mechanism for the phenotypic diversity in a patient carrying a rare ring chromosome 9].

OBJECTIVE: To explore the genetics mechanism for the phenotypic variability in a patient carrying a rare ring chromosome 9. METHODS: The karyotype of the patient was analyzed with cytogenetics method. Presence of sex chromosome was confirmed with fluorescence in situ hybridization. The SRY gene was subjected to PCR amplification and direct sequencing. Potential deletion and duplication were detected with array-based comparative genomic hybridization (array-CGH). RESULTS: The karyotype of the patient has comprised 6 types of cell lines containing a ring chromosome 9. The SRY gene sequence was normal. By array-CGH, the patient has carried a hemizygous deletion at 9p24.3-p23 (174 201-9 721 761) encompassing 30 genes from Online Mendelian Inheritance in Man. CONCLUSION: The phenotypic variability of the 9p deletion syndrome in conjunct with ring chromosome 9 may be attributable to multiple factors including loss of chromosomal material, insufficient dosage of genes, instability of ring chromosome, and pattern of inheritance.

[Detection of chromosomal aneuploidies in spontaneous abortion samples by fluorescence in situ hybridization].

OBJECTIVE: To analyze 81 spontaneous abortion samples with fluorescence in situ hybridization (FISH). METHODS: Chromosome 13, 21, 16, 22, 18, X and Y probes were used to detect the samples. RESULTS: FISH was successful in 80 cases (98.77%). Among these, 35 (43.75%) had an abnormal karyotype, which included 19 autosomal aneuploidies, 6 sex chromosome aneuploidies, 9 triploidies and 1 tetraploidy. CONCLUSION: FISH is a rapid and easy method for detecting chromosomal aneuploidies in spontaneous abortion samples, and has a higher detection rate in early spontaneous abortion samples.