Simultaneously Regulating Electrochemical Corrosion Behavior and Wettability of Magnesium-Neodymium Alloy by Self-Layered Chemical Conversion Coating.

Rapid corrosion in aqueous solutions of magnesium alloys is one of the major obstacles to their wide application, and coating plays a crucial role in their corrosion protection. Recently, protection- and function-integrated coatings have attracted much attention in the research field of magnesium alloys. In this work, a simple chemical conversion process is proposed to fabricate a composite coating on a magnesium-neodymium alloy through immersion in an aqueous solution made of Ca(OH)2 and NaHCO3. After the immersion process, a coating consisting of two spontaneously formed layers is acquired. The top flower-like layer is composed of Mg5(OH)2(CO3)4∙4H2O, Mg(OH)2 and CaCO3, and the inner dense layer is speculated to be Mg(OH)2. Electrochemical impedance spectroscopy, polarization tests, and hydrogen evolution are combined to evaluate the corrosion resistance in simulated body fluid, simulated seawater solution, and simulated concrete pore solution, which reveals that the coated sample has better corrosion resistance than the uncoated one. After the coated sample is modified with fluorinated silane, a water-repellent surface can be achieved with an average water contact angle of 151.74° and a sliding angle of about 4°. Therefore, our results indicate that effective corrosion protection and potential self-cleaning ability have been integrated on the surface of the magnesium alloy in this study. In addition, the formation mechanism of the self-layered coating is discussed from the viewpoint of the interaction between the substrate and its external solution.

A modular platform to generate functional sympathetic neuron-innervated heart assembloids.

The technology of human pluripotent stem cell (hPSC)-based 3D organoid/assembloid cultures has become a powerful tool for the study of human embryonic development, disease modeling and drug discovery in recent years. The autonomic sympathetic nervous system innervates and regulates almost all organs in the body, including the heart. Yet, most reported organoids to date are not innervated, thus lacking proper neural regulation, and hindering reciprocal tissue maturation. Here, we developed a simple and versatile sympathetic neuron (symN)-innervated cardiac assembloid without the need for bioengineering. Our human sympathetic cardiac assembloids (hSCAs) showed mature muscle structures, atrial to ventricular patterning, and spontaneous beating. hSCA-innervating symNs displayed neurotransmitter synthesis and functional regulation of the cardiac beating rate, which could be manipulated pharmacologically or optogenetically. We modeled symN-mediated cardiac development and myocardial infarction. This hSCAs provides a tool for future neurocardiotoxicity screening approaches and is highly versatile and modular, where the types of neuron (symN or parasympathetic or sensory neuron) and organoid (heart, lung, kidney) to be innervated may be interchanged.

Robust multiferroic in interfacial modulation synthesized wafer-scale one-unit-cell of chromium sulfide.

Multiferroic materials offer a promising avenue for manipulating digital information by leveraging the cross-coupling between ferroelectric and ferromagnetic orders. Despite the ferroelectricity has been uncovered by ion displacement or interlayer-sliding, one-unit-cell of multiferroic materials design and wafer-scale synthesis have yet to be realized. Here we develope an interface modulated strategy to grow 1-inch one-unit-cell of non-layered chromium sulfide with unidirectional orientation on industry-compatible c-plane sapphire. The interfacial interaction between chromium sulfide and substrate induces the intralayer-sliding of self-intercalated chromium atoms and breaks the space reversal symmetry. As a result, robust room-temperature ferroelectricity (retaining more than one month) emerges in one-unit-cell of chromium sulfide with ultrahigh remanent polarization. Besides, long-range ferromagnetic order is discovered with the Curie temperature approaching 200 K, almost two times higher than that of bulk counterpart. In parallel, the magnetoelectric coupling is certified and which makes 1-inch one-unit-cell of chromium sulfide the largest and thinnest multiferroics.

Extreme long-lifetime self-assembled monolayer for air-stable molecular junctions.

The molecular electronic devices based on self-assembled monolayer (SAM) on metal surfaces demonstrate novel electronic functions for device minimization yet are unable to realize in practical applications, due to their instability against oxidation of the sulfur-metal bond. This paper describes an alternative to the thiolate anchoring group to form stable SAMs on gold by selenides anchoring group. Because of the formation of strong selenium-gold bonds, these stable SAMs allow us to incorporate them in molecular tunnel junctions to yield extremely stable junctions for over 200 days. A detailed structural characterization supported by spectroscopy and first-principles modeling shows that the oxidation process is much slower with the selenium-gold bond than the sulfur-gold bond, and the selenium-gold bond is strong enough to avoid bond breaking even when it is eventually oxidized. This proof of concept demonstrates that the extraordinarily stable SAMs derived from selenides are useful for long-lived molecular electronic devices and can possibly become important in many air-stable applications involving SAMs.

Nucleosome assembly protein 1 like 1 (NAP1L1) promotes cardiac fibrosis by inhibiting YAP1 ubiquitination and degradation.

Myocardial fibrosis post myocardial infarction (MI) is characterized by abnormal extracellular matrix (ECM) deposition and cardiac dysfunction could finally develop into serious heart disease, like heart failure. Lots of regulating factors involved in this pathological process have been reported while the specific mediators and underlying mechanisms remain to need to be further investigated. As part of the NAP1 family, Nucleosome assembly protein 1 like 1 (NAP1L1) is expressed in a wide variety of tissues. Here, we report that NAP1L1 is a significant regulator of cardiac fibrosis and is upregulated in ischemic cardiomyopathy patient hearts. Enhanced expression of NAP1L1 can promote cardiac fibroblasts (CFs) proliferation, migration, and differentiation into myofibroblasts. In contrast, loss of NAP1L1 decreased fibrosis-related mRNA and protein levels, inhibited the trans-differentiation, and blunted migration and proliferation of CFs after Transforming Growth Factorß1（TGF-ß1）stimulation. In vivo, NAP1L1 knockout mice enhanced cardiac function and reduced fibrosis area in response to MI stimuli. Mechanically, NAP1L1 binding to Yes-associated protein 1 (YAP1) protein influences its stability, and silencing NAP1L1 can inhibit YAP1 expression by promoting its ubiquitination and degradation in CFs. Collectively, NAP1L1 could potentially be a new therapeutic target for various cardiac disorders, including myocardial fibrosis.

Decoding the mechanical conductance switching behaviors of dipyridyl molecular junctions.

Dipyridyl molecular junctions often show intriguing conductance switching behaviors with mechanical modulations, but the mechanisms are still not completely revealed. By applying the ab initio-based adiabatic simulation method, the configuration evolution and electron transport properties of dipyridyl molecular junctions in stretching and compressing processes are systematically investigated. The numerical results reveal that the dipyridyl molecular junctions tend to form specific contact configurations during formation processes. In small electrode gaps, the pyridyls almost vertically adsorb on the second Au layers of the tip electrodes by pushing the top Au atoms aside. These specific contact configurations result in stronger molecule-electrode couplings and larger electronic incident cross-sectional areas, which consequently lead to large breaking forces and high conductance. On further elongating the molecular junctions, the pyridyls shift to the top Au atoms of the tip electrodes. The additional scattering of the top Au atoms dramatically decreases the conductance and switches the molecular junctions to the lower conductive states. Perfect cyclical conductance switches are obtained as observed in the experiments by repeatedly stretching and compressing the molecular junctions. The O atom in the side-group tends to hinder the pyridyl from adsorbing on the second Au layer and further inhibits the conductance switch of the dipyridyl molecular junction.

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons.

The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the population suffer nerve degeneration or peripheral damage. For example, over 40% of patients with diabetes or undergoing chemotherapy develop peripheral neuropathies. Despite this, there are major gaps in the knowledge of human PNS development and therefore, there are no available treatments. Familial Dysautonomia (FD) is a devastating disorder that specifically affects the PNS making it an ideal model to study PNS dysfunction. FD is caused by a homozygous point mutation in ELP1 leading to developmental and degenerative defects in the sensory and autonomic lineages. We previously employed human pluripotent stem cells (hPSCs) to show that peripheral sensory neurons (SNs) are not generated efficiently and degenerate over time in FD. Here, we conducted a chemical screen to identify compounds able to rescue this SN differentiation inefficiency. We identified that genipin, a compound prescribed in Traditional Chinese Medicine for neurodegenerative disorders, restores neural crest and SN development in FD, both in the hPSC model and in a FD mouse model. Additionally, genipin prevented FD neuronal degeneration, suggesting that it could be offered to patients suffering from PNS neurodegenerative disorders. We found that genipin crosslinks the extracellular matrix, increases the stiffness of the ECM, reorganizes the actin cytoskeleton, and promotes transcription of YAP-dependent genes. Finally, we show that genipin enhances axon regeneration in an in vitro axotomy model in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system, CNS). Our results suggest genipin can be used as a promising drug candidate for treatment of neurodevelopmental and neurodegenerative diseases, and as a enhancer of neuronal regeneration.

In Situ Adjustable Nanogaps and In-Plane Break Junctions.

The ability to precisely regulate the size of a nanogap is essential for establishing high-yield molecular junctions, and it is crucial for the control of optical signals in extreme optics. Although remarkable strategies for the fabrication of nanogaps are proposed, wafer-compatible nanogaps with freely adjustable gap sizes are not yet available. Herein, two approaches for constructing in situ adjustable metal gaps are proposed which allow Ångstrom modulation resolution by employing either a lateral expandable piezoelectric sheet or a stretchable membrane. These in situ adjustable nanogaps are further developed into in-plane molecular break junctions, in which the gaps can be repeatedly closed and opened thousands of times with self-assembled molecules. The conductance of the single 1,4-benzenediamine (BDA) and the BDA molecular dimer is successfully determined using the proposed strategy. The measured conductance agreeing well with the data by employing another well-established scanning tunneling microscopy break junction technique provides insight into the formation of molecule dimer via hydrogen bond at single molecule level. The wafer-compatible nanogaps and in-plane dynamical break-junctions provide a potential approach to fabricate highly compacted devices using a single molecule as a building block and supply a promising in-plane technique to address the dynamical properties of single molecules.

Single-molecular insights into the breakpoint of cellulose nanofibers assembly during saccharification.

Plant cellulose microfibrils are increasingly employed to produce functional nanofibers and nanocrystals for biomaterials, but their catalytic formation and conversion mechanisms remain elusive. Here, we characterize length-reduced cellulose nanofibers assembly in situ accounting for the high density of amorphous cellulose regions in the natural rice fragile culm 16 (Osfc16) mutant defective in cellulose biosynthesis using both classic and advanced atomic force microscopy (AFM) techniques equipped with a single-molecular recognition system. By employing individual types of cellulases, we observe efficient enzymatic catalysis modes in the mutant, due to amorphous and inner-broken cellulose chains elevated as breakpoints for initiating and completing cellulose hydrolyses into higher-yield fermentable sugars. Furthermore, effective chemical catalysis mode is examined in vitro for cellulose nanofibers conversion into nanocrystals with reduced dimensions. Our study addresses how plant cellulose substrates are digestible and convertible, revealing a strategy for precise engineering of cellulose substrates toward cost-effective biofuels and high-quality bioproducts.

Room-Temperature Magnetoelectric Coupling in Atomically Thin ε-Fe2 O3.

2D multiferroics with magnetoelectric coupling combine the magnetic order and electric polarization in a single phase, providing a cornerstone for constructing high-density information storages and low-energy-consumption spintronic devices. The strong interactions between various order parameters are crucial for realizing such multifunctional applications, nevertheless, this criterion is rarely met in classical 2D materials at room-temperature. Here an ingenious space-confined chemical vapor deposition strategy is designed to synthesize atomically thin non-layered ε-Fe2 O3 single crystals and disclose the room-temperature long-range ferrimagnetic order. Interestingly, the strong ferroelectricity and its switching behavior are unambiguously discovered in atomically thin ε-Fe2 O3 , accompanied with an anomalous thickness-dependent coercive voltage. More significantly, the robust room-temperature magnetoelectric coupling is uncovered by controlling the magnetism with electric field and verifies the multiferroic feature of atomically thin ε-Fe2 O3 . This work not only represents a substantial leap in terms of the controllable synthesis of 2D multiferroics with robust magnetoelectric coupling, but also provides a crucial step toward the practical applications in low-energy-consumption electric-writing/magnetic-reading devices.

Preparing Thick Gradient Surface Layer in Cu-Zn Alloy via Ultrasonic Severe Surface Rolling for Strength-Ductility Balance.

A gradient structure (GS) design is a prominent strategy for strength-ductility balance in metallic materials, including Cu alloys. However, producing a thick GS surface layer without surface damage is still a challenging task limited by the available processing technology. In this work, a gradient structure (GS) surface layer with a thickness at the millimeter scale is produced in the Cu-38 wt.% Zn alloy using ultrasonic severe surface rolling technology at room temperature. The GS surface layer is as thick as 1.1 mm and involves the gradient distribution of grain size and dislocation density. The grain size is refined to 153.5 nm in the topmost surface layer and gradually increases with increasing depth. Tensile tests indicate that the single-sided USSR processed alloy exhibits balanced strength (467.5 MPa in yield strength) and ductility (10.7% in uniform elongation). Tailoring the volume fraction of the GS surface layer can tune the combination of strength and ductility in a certain range. The high strength of GS surface layer mainly stems from the high density of grain boundaries, dislocations and dislocation structures, deformation twins, and GS-induced synergistic strengthening effect. Our study elucidates the effect of the thick GS surface layer on strength and ductility, and provides a novel pathway for optimizing the strength-ductility combination of Cu alloys.

Following the Aggregation of Human Prion Protein on Heparin Functionalized Gold Surface in Real Time.

The aggregation of the prion protein (PrP) plays a key role in the development of prion diseases and is believed to be an autocatalytic process with a very high kinetic barrier. Intensive studies have focused on overcoming the kinetic barriers under extremely nonphysiological in vitro conditions by altering the pH of PrP solution on solid surfaces, such as gold, mica, and a lipid bilayer. Importantly, sulfated glycosaminoglycans (GAGs), including heparin, were found to be associated with PrP misfolding and aggregation, suggesting GAGs have catalytic roles in PrP aggregation processes. However, the exact role and details of GAGs in the PrP aggregation are not clear and need a thorough perusal. Here, we investigate the PrP aggregation process on a heparin functionalized gold surface by in situ, real-time monitoring of the atomic scale details of the whole aggregation process by single molecule atomic force microscopy (AFM), combining simultaneous topographic and recognition (TREC) imaging and single molecule force spectroscopy (SMFS). We observed the whole aggregation process for full-length human recombinant PrP (23-231) aggregation on the heparin modified gold surface, from the formation of oligomers, to the assembly of protofibrils and short fibers, and the formation of elongated mature fibers. Heparin is found to promote the PrP aggregation by facilitating the formation of oligomers during the early nucleation stage.

Details of Single-Molecule Force Spectroscopy Data Decoded by a Network-Based Automatic Clustering Algorithm.

Atomic force microscopy-single-molecule force spectroscopy (AFM-SMFS) is a powerful methodology to probe intermolecular and intramolecular interactions in biological systems because of its operability in physiological conditions, facile and rapid sample preparation, versatile molecular manipulation, and combined functionality with high-resolution imaging. Since a huge number of AFM-SMFS force-distance curves are collected to avoid human bias and errors and to save time, numerous algorithms have been developed to analyze the AFM-SMFS curves. Nevertheless, there is still a need to develop new algorithms for the analysis of AFM-SMFS data since the current algorithms cannot specify an unbinding force to a corresponding/each binding site due to the lack of networking functionality to model the relationship between the unbinding forces. To address this challenge, herein, we develop an unsupervised method, i.e., a network-based automatic clustering algorithm (NASA), to decode the details of specific molecules, e.g., the unbinding force of each binding site, given the input of AFM-SMFS curves. Using the interaction of heparan sulfate (HS)-antithrombin (AT) on different endothelial cell surfaces as a model system, we demonstrate that NASA is able to automatically detect the peak and calculate the unbinding force. More importantly, NASA successfully identifies three unbinding force clusters, which could belong to three different binding sites, for both Ext1f/f and Ndst1f/f cell lines. NASA has great potential to be applied either readily or slightly modified to other AFM-based SMFS measurements that result in "saw-tooth"-shaped force-distance curves showing jumps related to the force unbinding, such as antibody-antigen interaction and DNA-protein interaction.

Overlooked contributions of biochar-derived dissolved organic matter on the adsorption of Pb (â ¡): Impacts of fractionation and interfacial force.

Comprehensive understanding of how the release of biochar-derived dissolved organic matter (BDOM) affects the immobilization of heavy metals when biochar (BC) is applied for long-term soil remediation is extremely important. In this study, BCs prepared under different pyrolysis temperatures were fractionated into residual BC (RBC), nano-sized BC (NBC), and BDOM, in order to clarify the contribution of BDOM for lead (Pb(II)) adsorption on BC and to explore the interfacial mechanisms. Results demonstrated that the adsorption capacity (Qe) of Pb(II) on BC improved from 166.1 to 423.9 mg g-1 with the increase in the pyrolysis temperature from 350 to 800 °C. The sum of Qe of Pb(II) on NBC and RBC was lower than that on BC, due to the complexation between BDOM and Pb(II) rather than pH variance and cation exchange. Ultraviolet-visible and fluorescence spectroscopy revealed that fulvic-like substances as well as small molecules with low aromaticity in BDOM underwent favorable association with Pb(II) and got re-adsorbed on RBC. With the increase in the Pb(II) concentration, the contribution of van der Waals interaction for adsorption of BDOM350-Pb complexes was improved, whereas adsorption mechanism in BDOM800-Pb complexes was more dependent on ligand exchange. This study provides mechanistic insights into the impact of BDOM on Pb(II) immobilization, which can provide valuable information for the long-term remediation of Pb-contaminated soils using BC.

Hierarchical Self-Assembly of Nanowires on the Surface by Metallo-Supramolecular Truncated Cuboctahedra.

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.

Accuracy of brush cytology in biliopancreatic strictures: a single-center cohort study.

OBJECTIVE: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. METHODS: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course. RESULTS: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. CONCLUSIONS: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Double-Layered Supramolecular Prisms Self-Assembled by Geometrically Non-equivalent Tetratopic Subunits.

Supramolecular cages/vesicles in biology display sophisticated structures and functions by utilizing a few types of protein subunit quasi-equivalently at distinct geometrical locations. However, synthetic supramolecular cages still lack comparable complexity to reach the high levels of functionality found in natural systems. Herein we report the self-assembly of giant pentagonal supramolecular prisms (molecular weight >50 kDa) with tetratopic pyridinyl subunits serving different geometrical roles within the structures, and their packing into a novel superstructure with unexpected three-fold rotational symmetry in a single two-dimensional layer of crystalline state. The formation of these complicated structures is controlled by both the predetermined angles of the ligands and the mismatched structural tensions created from the multi-layered geometry of the building blocks. Such a self-assembly strategy is extensively used by viruses to increase the volume and complexity of capsids and would provide a new approach to construct highly sophisticated supramolecular architectures.

Metallo-Helicoid with Double Rims: Polymerization Followed by Folding by Intramolecular Coordination.

In this study, we established a feasible strategy to construct a new type of metallo-polymer with helicoidal structure through the combination of covalent polymerization and intramolecular coordination-driven self-assembly. In the design, a tetratopic monomer (M) was prepared with two terminal alkynes in the outer rim for polymerization, and two terpyridines (TPYs) in the inner rim for subsequent folding by selective intramolecular coordination. Then, the linear covalent polymer (P) was synthesized by polymerization of M via Glaser-Hay homocoupling reaction. Finally, intramolecular coordination interactions between TPYs and Zn(II) folded the backbone of P into a right- or left-handed metallo-helicoid (H) with double rims. Owing to multiple positive charges on the inner rim of helicoid, double-stranded DNA molecules (dsDNA) could interact with H through electrostatic interactions. Remarkably, dsDNA allowed exclusive formation of H with right handedness by means of chiral induction.

Plant cell wall hydrolysis process reveals structure-activity relationships.

BACKGROUND: Recent interest in Populus as a source of renewable energy, combined with its numerous available pretreatment methods, has enabled further research on structural modification and hydrolysis. To improve the biodegradation efficiency of biomass, a better understanding of the relationship between its macroscopic structures and enzymatic process is important. RESULTS: This study investigated mutant cell wall structures compared with wild type on a molecular level. Furthermore, a novel insight into the structural dynamics occurring on mutant biomass was assessed in situ and in real time by functional Atomic Force Microscopy (AFM) imaging. High-resolution AFM images confirmed that genetic pretreatment effectively inhibited the production of irregular lignin. The average roughness values of the wild type are 78, 60, and 30 nm which are much higher than that of the mutant cell wall, approximately 10 nm. It is shown that the action of endoglucanases would expose pure crystalline cellulose with more cracks for easier hydrolysis by cellobiohydrolase I (CBHI). Throughout the entire CBHI hydrolytic process, when the average roughness exceeded 3 nm, the hydrolysis mode consisted of a peeling action. CONCLUSION: Functional AFM imaging is helpful for biomass structural characterization. In addition, the visualization of the enzymatic hydrolysis process will be useful to explore the cell wall structure-activity relationships.

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration: A single-center analysis.

Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become an important modality for identification of intra-abdominal masses. This study analyzed the accuracy of EUS-FNAB in a single medical center and explored factors related to positive diagnosis. Materials and methods: In total, 77 patients with EUS-FNAB were retrospectively reviewed from July 2016 to February 2020. "Atypical (tends to be neoplasm/malignancy)," "suspicious (first consider neoplasm/malignancy)," and "malignant" were defined as positive cytology. The final diagnoses were based on histopathologic examination. The positive rate of EUS-FNAB for the diagnosis of neoplasm and its associations with age, sex, target puncture mass size, liver function, tumor markers, albumin, hypertension, and diabetes were examined. Results: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in all patients were 77.9% (60/77), 76.1% (54/71), 100%, 100%, and 26.1% (6/23), respectively. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in the pancreas were 80.0% (48/60), 79.3% (46/58), 100%, 100%, and 14.3% (2/14), respectively. The results of EUS-FNAB in pancreatic masses showed that the level of CA19-9 was higher in the true positive group than in the false-negative group (p<0.05). There were no factors associated with the true positive cytologic diagnoses (p>0.05). Conclusions: Our single-medical center study showed that EUS-FNAB is an accurate diagnostic procedure for the evaluation of intra-abdominal masses. Further follow-up is required to explore factors associated with the true positive cytology.