Data-driven discovery of a universal indicator for metallic glass forming ability.

Despite the importance of glass forming ability as a major alloy characteristic, it is poorly understood and its quantification has been experimentally laborious and computationally challenging. Here, we uncover that the glass forming ability of an alloy is represented in its amorphous structure far away from equilibrium, which can be exposed by conventional X-ray diffraction. Specifically, we fabricated roughly 5,700 alloys from 12 alloy systems and characterized the full-width at half-maximum, Δq, of the first diffraction peak in the X-ray diffraction pattern. A strong correlation between high glass forming ability and a large Δq was found. This correlation indicates that a large dispersion of structural units comprising the amorphous structure is the universal indicator for high metallic glass formation. When paired with combinatorial synthesis, the correlation enhances throughput by up to 100 times compared to today's state-of-the-art combinatorial methods and will facilitate the discovery of bulk metallic glasses.

A Good Aesthetic Outcome After Gross Total Tumor Resection in Combination With the Skull Reconstruction on Giant Epidermal Cyst Involving Both Intracranial and Extracranial Tissues.

ABSTRACT: Epidermal or epidermoid cysts are 1 of the most frequent benign masses, they rarely grow to a huge size, and only a few cases have been reported. We report a rare case of a 52-year-old man with giant neoplasm growing invasively in the frontal region, including both intracranial and extracranial extensions, and caused extensive brain deformation and skull lesions. It is worth noting that the patient did not present any significant neurological symptoms and deficits for more than 40 years on admission. A combination of gross total tumor resection and cranioplasty was performed. The patient was satisfied with the results of the surgery, and no evidence of recurrence or complications were found in the 2 years follow-up. The authors reported the case not only to propose the first-stage aesthetic treatment option for this unusual mass on the scalp but also hinted at the vigilance and importance of systematic monitoring of the small skull mass for avoiding the potential risk of tumor progression, malignant transformation, operative trauma, and financial burden.

[Clinical and genetic analysis of a novel CHD4 gene variant in a Chinese patient with Sifrim-Hitz-Weiss syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth. CONCLUSION: Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.

Macromolecule crowding effects on the phase separation of semi-flexible polymer in spherical confined space.

Current works focus on detecting macromolecule crowding effects on the phase separation of the mixture between semi-flexible polymer and crowders (hydrophilic polymers) in confined space by Monte Carlo simulations. With the increasing addition of crowders into the spherical confined space, the semi-flexible polymer was first compressed into a condensed state from the initial coil state, and then the condensed conformation expanded and deposited on the inner surface of the spherical confined space with an extended state. The phase diagram in the phase space of the volume fraction of crowders and the scaled radius of spherical confined space by crowder diameter, and the direct conformation transition of semi-flexible polymer have validated the phase transition process successfully. In addition, the deposition of extended conformation on the inner surface of the spherical confined space was qualified by the vertex density, its curve shifted along the radial direction with the increasing volume fraction of crowder. During the phase separation process, the critical volume fraction φ∗ relates to the crowder diameter approximately linearly and the relation between the critical volume fraction and the crowder diameter strongly depends on the size of the spherical confined space.

Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I.

Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353C>A (p.P118Q) in the SSUH2 gene on 3p26.1, which co-segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild-type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development.

A splicing mutation in VPS4B causes dentin dysplasia I.

BACKGROUND: Dentin dysplasia I (DDI) is a genetically heterogeneous autosomal-dominant disorder characterised by rootless teeth with abnormal pulpal morphology, the aetiology of which presents as genetically heterogeneous. METHODS AND RESULTS: Using a cohort of a large Chinese family with 10 patients with DDI, we mapped to a 9.63 Mb candidate region for DDI on chromosome 18q21.2-q21.33. We then identified a mutation IVS7+46C>G which resulted in a novel donor splice site in intron 7 of the VPS4B gene with co-segregation of all 10 affected individuals in this family. The aberrant transcripts encompassing a new insert of 45 bp in size were detected in gingival cells from affected individuals. Protein structure prediction showed that a 15-amino acid insertion altered the ATP-binding cassette of VPS4B. The mutation resulted in significantly reduced expression of mRNA and protein and altered subcellular localisation of VPS4B, indicating a loss of function of VPS4B. Using human gingival fibroblasts, the VPS4B gene was found to act as an upstream transducer linked to Wnt/ß-catenin signalling and regulating odontogenesis. Furthermore, knockdown of vps4b in zebrafish recapitulated the reduction of tooth size and absence of teeth similar to the tooth phenotype exhibited in DDI index cases, and the zebrafish mutant phenotype could be partially rescued by wild-type human VPS4B mRNA. We also observed that vps4b depletion in the zebrafish negatively regulates the expression of some major genes involved in odontogenesis. CONCLUSIONS: This study identifies VPS4B as a disease-causing gene for DDI, which is one of the important contributors to tooth formation, through the Wnt/ß-catenin signalling pathway.

Mitocytosis Mediated by an Enzyme-Activable Mitochondrion-Disturbing Polymer-Drug Conjugate Enhances Active Penetration in Glioblastoma Therapy.

The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, this work demonstrates a strategy of active transcellular transport of a mitochondrion-disturbing nanomedicine, pGBEMA22-b-pSSPPT9 (GBEPPT), in the GBM tissue through mitocytosis. GBEPPT is computer-aided designed and prepared by self-assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT). When GBEPPT is delivered to the tumor site, overexpressed γ-glutamyl transpeptidase (GGT) on the brain-blood endothelial cell, or the GBM cell triggered enzymatic hydrolysis of γ-glutamylamide on GBEPPT to reverse its negative charge to positive. Positively charged GBEPPT rapidly enter into the cell and target the mitochondria. These GBEPPT disturb the homeostasis of mitochondria, inducing mitocytosis-mediated extracellular transport of GBEPPT to the neighboring cells via mitosomes. This intracellular-to-intercellular delivery cycle allows GBEPPT to penetrate deeply into the GBM parenchyma, and exert sustainable action of PPT released from GBEPPT on the tumor cells along its penetration path at the tumor site, thus improving the anti-GBM effect. The process of mitocytosis mediated by the mitochondrion-disturbing nanomedicine may offer great potential in enhancing drug penetration through malignant tissues, especially poorly permeable solid tumors.

Quantification of macromolecule crowding at single-molecule level.

Macromolecule crowding has a prominent impact on a series of biochemical processes in the cell. It is also expected to promote macromolecular complexation induced by excluded volume effects, which conflicts with recent advances in the thermodynamic interaction between inert, synthetic polymers, and nucleic acids. Along this line, a method combining high-resolution magnetic tweezers and extended crowder-oxDNA model was applied to resolve these discrepancies by systematically studying the kinetics and thermodynamics of the folding-unfolding transition for an individual DNA hairpin in a crowded environment. More specifically, from the magnetic tweezers-based experiments, the linear dependence of the critical force of the DNA hairpin on the polyethylene glycol (PEG) concentration was demonstrated, which is consistent with the results based on the crowder-oxDNA model in which the Lennard-Jones potential was adopted to express the interaction between the crowders and the DNA hairpin. These consistencies highlight that the excluded volume effects are mainly responsible for the interaction between PEG and the DNA hairpin, which is different from the interaction between dextran and the DNA hairpin. In the meantime, the dependence of the folding rate on the molecule weight of PEG, which was different from fluorescence resonance energy transfer-based results, was identified. The proposed method opens a path to detect the interaction between an inert, synthetic molecule, and the DNA hairpin, which is important to accurately mimic the cytosolic environments using mixtures of different inert molecules.

The behavior between fluid and structure from coupling system of bile, bile duct, and polydioxanone biliary stent: A numerical method.

The performance and effects of 12 different structures of stents in the bile duct were compared and used the finite element method. Numerical models of the 12 kinds of fluid-structure interaction(FSI) coupling systems were established to investigate the relationship between three aspects (velocity distribution of bile, wall shear stress (WSS) distribution of bile, and Von Mises Stress(VMS) distribution on the stent and bile duct) and the structural parameters of the stent (monofilament diameter and the number of braiding heads). After calculating and analyzing the simulation results yielding distributions of velocity, WWS, and VMS and regions of bile duct susceptibility to stenosis, they were consistent with previous findings on the locations of restenosis occurring after stent removal, indicating that the simulation results could provide a useful reference for studying biliary stents. The results of the simulations showed that (i) eddy currents were prone to occur at the stent ends regions; (ii) the WSS distribution of the bile fluid in contact with the stent and bile duct related to the stent structure; (iii) the high VMS on the stent and bile duct was prone to occur at the stent ends. The simulation results of 12 FSI coupling systems were studied and two superior stent model structures were obtained by comprehensive evaluation.

Photothermal and Concus Finn capillary assisted superhydrophobic fibrous network enabling instant viscous oil transport for crude oil cleanup.

Rapid and effective removal of highly viscous oil spills from the sea remains a great challenge globally. Superhydrophobic materials are attractive candidates for handling oil spills, but they are restrained to recover oils with low viscosity exclusively. Herein, we report a novel polypyrrole wrapped superhydrophobic fibrous network using cross-shaped polyester fibers as starting blocks. The polypyrrole coating enables the absorbent to convert light to heat, ensuring that the viscosity of heavy oils in the proximity can be easily controlled. In the meanwhile, the special structure of the starting fibers initiates Concus Finn (CFin) capillary allowing instant oil transport in the network. When the absorbent is exposed to light oils (0-500 mPa.s), the oils can be transported instantly via CFin capillary. Interestingly, under synergistic effect of light-to-heat conversion and CFin capillary, a drawing-sticking crude oil strip (105 mPa.s) is sucked instantly against gravity by the absorbent. The absorbent is successfully applied to efficiently separate both oil/water mixtures and oil/water emulsions (efficiency > 99%). Such absorbent can absorb 62.99-74.23 g/g light oils on average and up to 123.3 g/g crude oil under 0-2 sun illumination, holding a huge potential in managing oil spills.

Exploring the brachistochrone (shortest-time) path in fire spread.

The brachistochrone (shortest-time) curve is the path connecting two points that enables the shortest travel time. This work explores the "brachistochrone path" of fire spread connecting two points at the same altitude and with a fixed path length. The starting and ending points are connected by both thermally thin fuels (thin wires) and thermally thick fuels (PMMA bars). Flame-spread paths of triangular, rectangular, and circular shapes with different heights and inclinations are explored. Results show that having a local maximum flame-spread rate does not result in the shortest overall travel time. For thin-wire paths, the fastest overall-path fire spread occurs, when the upward spread path is vertical, and the path height reaches a maximum, as demonstrated by the theoretical analysis. Differently, for thick PMMA-bar paths, the brachistochrone condition occurs when the path length of the vertical upward spread reaches the maximum, because the upward spread is about ten times faster than the downward spread. This study extends the conventional problem of the fastest fire spread to the shortest-time problem of the whole fire path, and it may help optimize the fuel distribution inside the built environment and estimate available safe egress time in building and wildland fires.

Recycling Potential of Plastic Resources from End-of-Life Passenger Vehicles in China.

A rapid increase in the number of end-of-life (EoL) passenger vehicles has led to a large amount of waste plastics in China. However, the scale and efficiency of recycling resources from EoL vehicles still restricts the sustainable and healthy development of the automotive industry. The current behavior of automotive/recycling industry entities, as well as the strategy of waste management policymakers, may depend on the potential of total recyclable resources. To reveal such recycling potential of various plastic materials in EoL passenger vehicles, we predicted total EoL passenger vehicles in China from 2021 to 2030 (used the Weibull distribution) considering passenger vehicle ownership (estimated by the Gompertz model), quantified the demand for new passenger vehicles (estimated using its non-linear relationship with income level and passenger vehicle ownership), and assessed the recyclable plastics by categories and by provinces. The results show that (i) the annual average recycled plastic resources from EoL vehicles would exceed 2400 thousand t in 2030, more than 2.5 times in 2021, showing a great recycling potential; (ii) the differences among the three scenarios are relatively small, indicating that no matter the saturation level of passenger vehicles in China would be high or low, a rapid increase of recyclable plastic resources can be expected from 2021 to 2030; (iii) at the provincial level, a considerable gap between the potential of recycling plastic from EoL passenger vehicles and the regional processing capacity. Given such great potential and regional differences, the recycling policies should be applied in stages and consider the development level and recovery pressure in each region.

[Experimental research on osteogenic abilities of new bone tissue engineering scaffolds by recombinant bone morphogenetic protein].

This research sought to asses the efficacity of a new type of tissue engineering bone developed by PDLLA/ PLA-PEG-PLA and BMP as a kind of bone graft substitute in the rabbit model of mandibular defects; 15 mm x 6 mm bilateral mandibular periosteum bone defects were made surgically in 20 New Zealand adult rabbits. The porous scaffolds impregnated with rhBMP-2 were used for the purpose, and the scaffolds without rhBMP-2 were used as control. The methods adopted in this research were: macroscopy, histomorphologic exam, X-ray exam, SEM micrography, computer-aided analysis and graphics. The experimental group was shown to have an earlier inception of bone forming. New bone formation was seen along the border of the original mandibular bone and in the middle. At 12 weeks after surgery,the defects were almost filled with new bone. In the control group, the defects could not be repaired in its entirety, and there was no new bone in the middle. The porous scaffold is a promising carrier for BMP. This kind of bone graft substitute can serve as an osteoconductive and osteoinductive matrix.

Bending behaviors of fully covered biodegradable polydioxanone biliary stent for human body by finite element method.

This paper presents a study of the bending flexibility of fully covered biodegradable polydioxanone biliary stents (FCBPBs) developed for human body. To investigate the relationship between the bending load and structure parameter (monofilament diameter and braid-pin number), biodegradable polydioxanone biliary stents derived from braiding method were covered with membrane prepared via electrospinning method, and nine FCBPBSs were then obtained for bending test to evaluate the bending flexibility. In addition, by the finite element method, nine numerical models based on actual biliary stent were established and the bending load was calculated through the finite element method. Results demonstrate that the simulation and experimental results are in good agreement with each other, indicating that the simulation results can be provided a useful reference to the investigation of biliary stents. Furthermore, the stress distribution on FCBPBSs was studied, and the plastic dissipation analysis and plastic strain of FCBPBSs were obtained via the bending simulation.

Applications of LC/MS in structure identifications of small molecules and proteins in drug discovery.

With advancements in ionization methods and instrumentation, liquid chromatography/mass spectrometry (LC/MS) has become a powerful technology for the characterization of small molecules and proteins. This article will illustrate the role of LC/MS analysis in drug discovery process. Examples will be given on high-throughput analysis, structural analysis of trace level impurities in drug substances, identification of metabolites, and characterization of therapeutic protein products for process improvement. Some unique MS techniques will also be discussed to demonstrate their effectiveness in facilitating structural identifications.

How Many Bulk Metallic Glasses Are There?

Quantitative prediction of glass forming ability using a priori known parameters is highly desired in metallic glass development; however proven to be challenging because of the complexity of glass formation. Here, we estimate the number of potential metallic glasses (MGs) and bulk metallic glasses (BMGs) forming systems and alloys, from empirically determined alloy design rules based on a priori known parameters. Specifically, we take into account atomic size ratio, heat of mixing, and liquidus temperature, which we quantify on binary glasses and centimeter-sized BMGs. When expanding into higher order systems that can be formed among 32 practical elements, we reduce the composition space for BMG formation using developed criteria by 106 times and estimate ∼3 million binary, ternary, quaternary, and quinary BMGs alloys.

Expression of hypoxia inducible factor-2 alpha in overloaded- stress induced destruction of mandibular condylar chondrocytes.

OBJECTIVE: To study the protein expression of HIF-2α in condylar chondrocytes under the different stress loading, to investigate the possible effects of HIF-2α involved in the mortality of condylar chondrocytes under overloaded- stress. MATERIALS AND METHODS: Chondrocytes were isolated from TMJ condylar cartilage and cultured in hypoxia-incubator. Chondrocytes were divided into 4 groups: 0, 1000, 2000, 3000 ustrain group, which was subjected to cyclic tensile strain (CTS) of 0.5Hz for 2h. The rate of cell mortality was calculated. Western blot was used to measure the expression of HIF-2α and it's downstream catabolic factors (MMP3, MMP13, ADAMTS4) in protein levels respectively. RESULTS: With the increase of CTS, both of the rate of cell mortality and protein expression of HIF-2α increased significantly (p<0.05). The same tendency was also found in it's downstream catabolic factors (MMP3, MMP13, ADAMTS4) in protein levels (p<0.05). CONCLUSIONS: The results indicated that elevated expression of HIF-2α may be a possible mechanism related to overloaded- stress induced mortality of condylar chondrocytes.

Mussel-Inspired Multifunctional Hydrogel Coating for Prevention of Infections and Enhanced Osteogenesis.

Prevention of postsurgery infection and promotion of biointegration are the key factors to achieve long-term success in orthopedic implants. Localized delivery of antibiotics and bioactive molecules by the implant surface serves as a promising approach toward these goals. However, previously reported methods for surface functionalization of the titanium alloy implants to load bioactive ingredients suffer from time-consuming complex processes and lack of long-term stability. Here, we present the design and characterization of an adhesive, osteoconductive, and antimicrobial hydrogel coating for Ti implants. To form this multifunctional hydrogel, a photo-cross-linkable gelatin-based hydrogel was modified with catechol motifs to enhance adhesion to Ti surfaces and thus promote coating stability. To induce antimicrobial and osteoconductive properties, a short cationic antimicrobial peptide (AMP) and synthetic silicate nanoparticles (SNs) were introduced into the hydrogel formulation. The controlled release of AMP loaded in the hydrogel demonstrated excellent antimicrobial activity to prevent biofilm formation. Moreover, the addition of SNs to the hydrogel formulation enhanced osteogenesis when cultured with human mesenchymal stem cells, suggesting the potential to promote new bone formation in the surrounding tissues. Considering the unique features of our implant hydrogel coating, including high adhesion, antimicrobial capability, and the ability to induce osteogenesis, it is believed that our design provides a useful alternative method for bone implant surface modification and functionalization.

Enhancing the anti-glioma therapy of doxorubicin by honokiol with biodegradable self-assembling micelles through multiple evaluations.

Combination chemotherapy is an important protocol in glioma therapy and honokiol shows synergistic anticancer effects with doxorubicin. In this paper, honokiol (HK) and doxorubicin (Dox) co-loaded Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) nanoparticles were prepared with a assembly method. The particle size (about 34 nm), morphology, X-ray Powder Diffraction (XRD), in vitro release profile, cytotoxicity and cell proliferation effects were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PCL nanoparticles simultaneously, and could be released from the micelles in an extended period in vitro. In addition, honokiol and doxorubicin loaded in MPEG-PCL nanoparticles could efficiently suppress glioma cell proliferation and induce cell apoptosis in vitro. Furthermore, Dox-HK-MPEG-PCL micelles inhibited glioma growth more significantly than Dox-MPEG-PCL and HK-MPEG-PCL in both nude mice and zebrafish tumor models. Immunohistochemical analysis indicated that DOX-HK-MPEG-PCL micelles improved Dox's anti-tumor effect by enhancing tumor cell apoptosis, suppressing tumor cell proliferation, and inhibiting angiogenesis. Our data suggest that Dox-HK-MPEG-PCL micelles have the potential to be applied clinically in glioma therapy.

Exploring a wider range of Mg-Ca-Zn metallic glass as biocompatible alloys using combinatorial sputtering.

In order to bypass the limitation of bulk metallic glasses fabrication, we synthesized thin film metallic glasses to study the corrosion characteristics of a wide atomic% composition range, Mg(35.9-63%)Ca(4.1-21%)Zn(17.9-58.3%), in simulated body fluid. We highlight a clear relationship between Zn content and corrosion current such that Zn-medium metallic glasses exhibit minimum corrosion. In addition, we found higher Zn content leads to a poor in vitro cell viability. These results showcase the benefit of evaluating a larger alloy compositional space to probe the limits of corrosion resistance and prescreen for biocompatible applications.