Molecular Interaction Mechanisms Between Lubricant-Infused Slippery Surfaces and Mussel-Inspired Polydopamine Adhesive and DOPA Moiety.

Lubricant-infused slippery surfaces have recently emerged as promising antifouling coatings, showing potential against proteins, cells, and marine mussels. However, a comprehensive understanding of the molecular binding behaviors and interaction strength of foulants to these surfaces is lacking. In this work, mussel-inspired chemistry based on catechol-containing chemicals including 3,4-dihydroxyphenylalanine (DOPA) and polydopamine (PDA) is employed to investigate the antifouling performance and repellence mechanisms of fluorinated-based slippery surface, and the correlated interaction mechanisms are probed using atomic force microscopy (AFM). Intermolecular force measurements and deposition experiments between PDA and the surface reveal the ability of lubricant film to inhibit the contact of PDA particles with the substrate. Moreover, the binding mechanisms and bond dissociation energy between a single DOPA moiety and the lubricant-infused slippery surface are quantitatively investigated employing single-molecule force spectroscopy based on AFM (SM-AFM), which reveal that the infused lubricant layer can remarkably influence the dissociation forces and weaken the binding strength between DOPA and underneath per-fluorinated monolayer surface. This work provides new nanomechanical insights into the fundamental antifouling mechanisms of the lubricant-infused slippery surfaces against mussel-derived adhesive chemicals, with important implications for the design of lubricant-infused materials and other novel antifouling platforms for various bioengineering and engineering applications.

Target Enclosing and Coverage Control for Quadrotors with Constraints and Time-Varying Delays: A Neural Adaptive Fault-Tolerant Formation Control Approach.

This paper investigates the problem of formation fault-tolerant control of multiple quadrotors (QRs) for a mobile sensing oriented application. The QRs subject to faults, input saturation and time-varying delays can be controlled to perform a target-enclosing and covering task while guaranteeing the state constraints will not be exceeded. A distributed formation control scheme is proposed, using a radial basis function neural network (RBFNN)-based time-delay position controller and an adaptive fault-tolerant attitude controller. The Lyapunov-Krasovskii approach is used to analyze the time-varying delay. Barrier Lyapunov function is deployed to handle the prescribed constraints, and an auxiliary system combined with a command filter is designed to resolve the saturation problem. An RBFNN and adaptive estimators are deployed to provide estimates of disturbances, fault signals and uncertainties. It is proven that all the closed-loop signals are bounded under the proposed protocol, while the prescribed constraints will not be violated, which enhances the flight safety and QR formation's applicability. Comparative simulations based on application scenarios further verify the effectiveness of the proposed method.

In silico study on graphene quantum dots modified with various functional groups inhibiting α­synuclein dimerization.

HYPOTHESIS: Graphene quantum dots (GQDs) with various functional groups are hypothesized to inhibit the α-synuclein (αS) dimerization, a crucial step in Parkinson's disease pathogenesis. The potential of differently functionalized GQDs is systematically explored. EXPERIMENTS: All-atom replica-exchange molecular dynamics simulations (accumulating to 75.6 µs) in explicit water were performed to study the dimerization of the αS non-amyloid component region and the influence of GQDs modified with various functional groups. Conformation ensemble, binding behavior, and free energy analysis were conducted. FINDINGS: All studied GQDs inhibit ß-sheet and backbone hydrogen bond formation in αS dimers, leading to looser oligomeric conformations. Charged GQDs severely impede the growth of extended ß-sheets by providing extra contact surface. GQD binding primarily disrupts αS inter-peptide interactions through π-π stacking, CH-π interactions, and for charged GQDs, additionally through salt-bridge and hydrogen bonding interactions. GQD-COO- showed the most optimal inhibitory effect, binding mode, and intensity, which holds promise for the development of nanomedicines targeting amyloid aggregation in neurodegenerative diseases.

Sources, colloidal characteristics, and separation technologies for highly hazardous waste nanoemulsions.

Nanoemulsions play a crucial role in various industries. However, their application often results in hazardous waste, posing significant risks to human health and the environment. Effective management and separation of waste nanoemulsions requires special attention and effort. This review provides a comprehensive understanding of waste nanoemulsions, covering their sources, characteristics, and suitable treatment technologies, intending to mitigate their environmental impact. This study examines the evolution of nanoemulsions from beneficial products to hazardous wastes, provides an overview of the production processes, fate, and hazards of waste nanoemulsions, and highlights the critical characteristics that affect their stability. The latest advancements in separating waste nanoemulsions for recovering oil and reusable water resources are also presented, providing a comprehensive comparison and evaluation of the current treatment techniques. This review addresses the significant challenges in nanoemulsion treatment, provides insights into future research directions, and offers valuable implications for the development of more effective strategies to mitigate the hazards associated with waste nanoemulsions.

Dual-Protection Inorganic-Protein Coating on Mg-Based Biomaterials through Tooth-Enamel-Inspired Biomineralization.

Biocompatible magnesium alloys represent revolutionary implantable materials in dentistry and orthopedics but face challenges due to rapid biocorrosion, necessitating protective coatings to mitigate dysfunction. Directly integrating durable protective coatings onto Mg surfaces is challenging because of intrinsic low coating compactness. Herein, inspired by tooth enamel, a novel highly compact dual-protection inorganic-protein (inorganicPro) coating is in situ constructed on Mg surfaces through bovine serum albumin (BSA) protein-boosted reaction between sodium fluoride (NaF) and Mg substrates. The association of Mg ions and BSA establishes a local hydrophobic domain that lowers the formation enthalpy of NaMgF3 nanoparticles. This process generates finer nanoparticles that function as "bricks," facilitating denser packing, consequently reducing voidage inside coatings by over 50% and reinforcing mechanical durability. Moreover, the incorporation of BSA in and on the coatings plays two synergistic roles: 1) acting as "mortar" to seal residual cracks within coatings, thereby promoting coating compactness and tripling anticorrosion performance, and 2) mitigating fouling-accelerated biocorrosion in complex biosystems via tenfold resistance against biofoulant attachments, including biofluids, proteins, and metabolites. This innovative strategy, leveraging proteins to alter inorganic reactions, benefits the future coating design for Mg-based and other metallic materials with tailored anticorrosion and antifouling performances.

Formation and Nanomechanical Properties of Silver-Mediated Guanine DNA Duplexes in Aqueous Solution.

Silver cations can mediate base pairing of guanine (G) DNA oligomers, yielding linear parallel G-Ag+-G duplexes with enhanced stabilities compared to those of canonical DNA duplexes. To enable their use in programmable DNA nanotechnologies, it is critical to understand solution-state formation and the nanomechanical stiffness of G-Ag+-G duplexes. Using temperature-controlled circular dichroism (CD) spectroscopy, we find that heating mixtures of G oligomers and silver salt above 50 °C fully destabilizes G-quadruplex structures and converts oligomers to G-Ag+-G duplexes. Electrospray ionization mass spectrometry supports that G-Ag+-G duplexes form at stoichiometries of 1 Ag+ per base pair, and CD spectroscopy suggests that as the Ag+/base stoichiometry increases further, G-Ag+-G duplexes undergo additional morphological changes. Using liquid-phase atomic force microscopy, we find that this excess Ag+ enables assembly of long fiberlike structures with ∼2.5 nm heights equivalent to a single DNA duplex but with lengths that far exceed a single duplex. Finally, using the conditions established to form single G-Ag+-G duplexes, we use a surface forces apparatus (SFA) to compare the solution-phase stiffness of single G-Ag+-G duplexes with dG-dC Watson-Crick-Franklin duplexes. SFA shows that G-Ag+-G duplexes are 1.3 times stiffer than dG-dC duplexes, confirming gas-phase ion mobility spectrometry measurements and computational predictions. These findings may guide the development of structural DNA nanotechnologies that rely on silver-mediated base pairing.

Larger aggregate formed by self-assembly process of the mixture surfactants enhance the dissolution and oxidative removal of non-aqueous phase liquid contaminants in aquifer.

Surfactants can transfer non-aqueous phase liquid (NAPL) contaminants to the aqueous phase, and enhance the removal of the latter in groundwater. However, the extensive use of surfactants causes secondary contamination and increases the non-target consumption of oxidants. It is pressing to develop a surfactant with high phase transfer efficiency and sound compatibility with oxidants to minimize the use of surfactants for groundwater remediation. The phase transfer capability of different surfactants and their binary mixtures, their enhanced KMnO4 oxidation performance for NAPL contaminants as well as influencing factors were investigated to solve the above-mentioned question. The results showed that Tween20, SDBS and BS-12 perform best in terms of phase transfer capability among nonionic, anionic and amphoteric surfactants respectively, and only SDBS and BS-12 produce a synergistic effect among the binary mixtures. The CMC of SDBS/BS-12 was lower than its ideal CMC value, and the self-assembly process of SDBS/BS-12 also formed larger aggregates, which improved the phase transfer performance. Compared to other single surfactants, the removal efficiency of petroleum hydrocarbons in the aquifer sediments was raised by 7.4-33.8 % using the mixed surfactant. The SDBS/BS-12 mixture was compatible with KMnO4 and boosted the reaction of NAPL contaminants with KMnO4 by transferring from the NAPL phase to the aqueous phase. As a result, the NAPL toluene and phenanthrene removal efficiency increased from 37 % and 29 % to 80 % and 86 % respectively. Natural organic matters inhibited the phase transfer efficiency of the SDBS/BS-12 mixture, whereas anions and monovalent cations enhanced the phase transfer capability of the mixture. High-valent cations led to precipitation in the SDBS/BS-12, which could be eliminated by adding Na2Si2O5. The SDBS/BS-12 mixture delivered the same phase transfer efficiency with the dosage of 1.73-23.07 % of other single surfactants, and its cost was equivalent to 0.25-41.7 % of the latter, thus embracing bright application prospects.

Recent advances in fabricating injectable hydrogels via tunable molecular interactions for bio-applications.

Hydrogels with three-dimensional structures have been widely applied in various applications because of their tunable structures, which can be easily tailored with desired functionalities. However, the application of hydrogel materials in bioengineering is still constrained by their limited dosage flexibility and the requirement of invasive surgical procedures. Compared to traditional hydrogels, injectable hydrogels, with shear-thinning and/or in situ formation properties, simplify the implantation process and reduce tissue invasion, which can be directly delivered to target sites using a syringe injection, offering distinct advantages over traditional hydrogels. These injectable hydrogels incorporate physically non-covalent and/or dynamic covalent bonds, granting them self-healing abilities to recover their structural integrity after injection. This review summarizes our recent progress in preparing injectable hydrogels and discusses their performance in various bioengineering applications. Moreover, the underlying molecular interaction mechanisms that govern the injectable and functional properties of hydrogels were characterized by using nanomechanical techniques such as surface forces apparatus (SFA) and atomic force microscopy (AFM). The remaining challenges and future perspectives on the design and application of injectable hydrogels are also discussed. This work provides useful insights and guides future research directions in the field of injectable hydrogels for bioengineering.

Analysis of volatiles from the thermal decomposition of Amadori rearrangement products in the cysteine-glucose Maillard reaction and density functional theory study.

The Amadori rearrangement products are an important flavor precursor in the Maillard reaction. Its thermal decomposition products usually contribute good flavors in foods. Therefore, investigating the thermal breakdown of Amadori products is significant for understanding the flavor forming mechanism in the Maillard reaction. In this study, volatiles from thermal decomposition of Amadori products in cysteine and glucose Maillard reaction was investigated by a thermal desorption cryo-trapping system combined with gas chromatography-mass spectrometry (GC-MS). A total of 60 volatiles were detected and identified. Meanwhile, the forming mechanism of 2-methylthiophene, a major decomposition product, was also investigated by using density functional theory. Seventeen reactions, 12 transition states, energy barrier and rate constant of each reaction were finally obtained. Results reveal that it is more likely for Amadori products of cysteine and glucose to undergo decomposition under neutral or weakly alkaline conditions.

Probing the interfacial behaviors of interfacially active and non-active asphaltenes and their impact on emulsion stability.

HYPOTHESIS: Asphaltenes subfractions with distinct interfacial behaviors may play different roles in stabilizing oil-water emulsions. EXPERIMENTS: In this work, whole asphaltenes were separated into interfacially active asphaltenes (IAA) and interfacially non-active asphaltenes (INAA). Employing advanced nanomechanical techniques, we have explored the compositions, morphologies, sizes, adsorption, and interfacial behaviors of IAA and INAA. FINDINGS: IAA exhibits a high and unevenly distributed oxygen content, distinguishing it from INAA. In toluene, the diameters of IAA and INAA are about 60 nm and 6 nm, respectively. When adsorbed irreversibly on mica surfaces, the thickness of the IAA and INAA film was measured at âˆ¼5.5 nm or 1 nm, respectively; while in a toluene solution, the film thickness reached âˆ¼46 nm and 3.1 nm for IAA and INAA, respectively. IAA demonstrates superior interfacial activity, and elastic/viscous moduli compared to INAA at the water-toluene interface. Quantified surface force measurements reveal that IAA stabilizes water droplets in toluene at a concentration of only 10 mg/L, while INAA requires a higher concentration of 100 mg/L. This work provides the first comprehensive investigation into the adsorption and interfacial behaviors of asphaltene subfractions and provides useful insights into the asphaltenes-stabilization mechanism of emulsions.

Bionic Engineered Protein Coating Boosting Anti-Biofouling in Complex Biological Fluids.

Implantable medical devices have been widely applied in diagnostics, therapeutics, organ restoration, and other biomedical areas, but often suffer from dysfunction and infections due to irreversible biofouling. Inspired by the self-defensive "vine-thorn" structure of climbing thorny plants, a zwitterion-conjugated protein is engineered via grafting sulfobetaine methacrylate (SBMA) segments on native bovine serum albumin (BSA) protein molecules for surface coating and antifouling applications in complex biological fluids. Unlike traditional synthetic polymers of which the coating operation requires arduous surface pretreatments, the engineered protein BSA@PSBMA (PolySBMA conjugated BSA) can achieve facile and surface-independent coating on various substrates through a simple dipping/spraying method. Interfacial molecular force measurements and adsorption tests demonstrate that the substrate-foulant attraction is significantly suppressed due to strong interfacial hydration and steric repulsion of the bionic structure of BSA@PSBMA, enabling coating surfaces to exhibit superior resistance to biofouling for a broad spectrum of species including proteins, metabolites, cells, and biofluids under various biological conditions. This work provides an innovative paradigm of using native proteins to generate engineered proteins with extraordinary antifouling capability and desired surface properties for bioengineering applications.

Surface interaction mechanisms of air bubbles, asphaltenes and oil drops in aqueous solutions with implications for interfacial engineering processes.

HYPOTHESIS: Surface interactions of bubbles and oil with interface-active species like asphaltenes influence many interfacial phenomena in various engineering processes. It holds both fundamental and practical significance to quantitatively characterize these interactions. EXPERIMENTS: The surface forces of air bubbles, asphaltenes and asphaltenes-toluene droplets in various aqueous solutions have been quantified using an integrated thin film drainage apparatus and an atomic force microscope coupled with bubble probe. The effects of asphaltenes concentration, pH, salinity, Ca2+ ions and surfactants have been examined. FINDINGS: Hydrophobic interaction drives attachment of bubbles and asphaltenes surfaces or oil droplets under high salinity condition. Increasing asphaltenes concentration in oil droplets enhances their hydrophobic attraction with bubbles due to strengthened asphaltenes adsorption and aggregation at oil-water interface. Increasing pH weakens the hydrophobic interaction as oil surfaces become more negatively charged and less hydrophobic. Under low salinity condition, strong electrical double layer and van der Waals repulsion inhibits the bubble-oil droplet contact. Introducing Ca2+ ions and surfactants leads to strong steric repulsion, preventing bubble-oil contact. This research has advanced our mechanistic understanding of how bubbles and oil droplets interact in aqueous systems and offers useful insights to modulate such interactions in oil production, water treatment and other interfacial processes.

Blowing-inspired ex situ preparation of ultrathin hydrogel coatings for visibly monitoring humidity and alkaline gas.

Compared with the in situ preparation of ultrathin hydrogel coatings through successive yet tedious steps, ex situ strategies decouple the steps and greatly enhance the maneuverability and convenience of preparing hydrogel coatings. However, the difficulty in preparing sub-micron-thick coatings limits the applicability of ex situ methods in nanotechnology. Herein, we report the ex situ preparation of centimeter-scale ultrathin hydrogel coatings by applying omnidirectional stretching toward pre-gelated hydrogels with necking behaviors. This process involves blowing a bubble directly from a pre-gelated hydrogel and subsequently transferring the resulting hydrogel bubble to different substrates. The as-fabricated coatings exhibit peak-shaped thickness variations, with the thinnest part as low as ∼5 nm and the thickest part controllable from ∼200 nm to several microns. This method can be universally applied to hydrogels with necking behavior triggered by internal particles with partial hydrophobicity. Due to the overall near- or sub-micron thickness and unique thickness distribution, the coatings present concentric rings of different interference colors. With such an observable optical characteristic, the as-prepared hydrogel coatings are applied as sensors to visibly monitor humidity changes or alkaline gas through the visibly observable expansion or contraction of concentric interferometry rings, which is triggered by adsorbing/desorbing the surrounding water or alkaline molecules and the resultant swelling/deswelling of the coatings, respectively. With the universality of the method, we believe that the ex situ strategy can be used as a simple yet efficient environmental nanotechnology to fabricate various types of nanometer-thick hydrogel coatings as detectors to sensitively and visibly monitor surrounding stimuli on demand.

Bioinspired engineered proteins enable universal anchoring strategy for surface functionalization.

HYPOTHESIS: Conventional coating strategies and materials for bio-applications with protective, diagnostic, and therapeutic functions are commonly limited by their arduous preparation processes and lack of on-demand functionalities. Herein, inspired by the 'root-leaf' structure of grass, a series of novel polyacrylate-conjugated proteins can be engineered with sticky bovine serum albumin (BSA) protein as a 'root' anchoring layer and a multifunctional polyacrylate as a 'leaf' functional layer for the facile coating procedure and versatile surface functionalities. EXPERIMENTS: The engineered proteins were synthesized based on click chemistry, where the 'root' layer can universally anchor onto both organic and inorganic substrates through a facile dip/spraying method with excellent stability in harsh solution conditions, thanks to its multiple adaptive molecular interactions with substrates that further elucidated by molecular force measurements between the 'root' BSA protein and substrates. The 'leaf' conjugated-polyacrylates imparted coatings with versatile on-demand functionalities, such as resistance to over 99% biofouling in complex biofluids, pH-responsive performance, and robust adhesion with various nanomaterials. FINDINGS: By synergistically leveraging the universal anchoring capabilities of BSA with the versatile physicochemical properties of polyacrylates, this study introduces a promising and facile strategy for imparting novel functionalities to a myriad of surfaces through engineering natural proteins and biomaterials for biotechnical and nanotechnical applications.

How Do Environmental Regulations and Outward Foreign Direct Investment Impact the Green Total Factor Productivity in China? A Mediating Effect Test Based on Provincial Panel Data.

This paper investigates the impact of two types of environmental regulations (ERs), command-and-control environmental regulation (CACER) and market-incentive environmental regulation (MIER), on green total factor productivity (GTFP) through outward foreign direct investment (OFDI) in 30 provinces in China for the period of 2006-2019. The Global Malmquist-Luenberger (GML) Index based on non-radial directional distance function (NDDF) considering undesired outputs is used to measure GTFP growth at the provincial level. To explore the mediating effect of OFDI, the two-step econometric model and the non-linear mediating effect model are employed. The empirical results show that CACER has an inverted U-shaped impact on OFDI and a U-shaped impact on GTFP, while MIER has a linearly positive effect on OFDI and GTFP. The current intensity of CACER lies on the left side of the inflection point of the U-shaped curve. OFDI significantly positively influences the increase in GTFP and is a significant mediating variable in the relationship between ERs and GTFP. Moreover, the introduction of OFDI delays the appearance of the inflection point. Further analysis, taking into account the regional heterogeneity, indicates that the inverted U-shaped and U-shaped curve is still valid in the eastern and western area and that the mediating effect of OFDI on ERs in the western area is stronger than that in the eastern area. Based on these conclusions, policy implications are provided to improve GTFP in China.

Influencing Factors on the Household-Waste-Classification Behavior of Urban Residents: A Case Study in Shanghai.

As the process of urbanization in China continues to accelerate, the amount of domestic waste generated correspondingly increases and directly affects the living space of residents. This indirectly implies that to reduce the production of municipal solid waste and the need for garbage disposal and recycling, household-waste-classification activities by the residents are of great significance. Using Shanghai as a case study, this study investigated the influencing factors on residents' household waste classification by conducting a survey. Statistical analysis was then adopted, which is specified below. First, this study proposed research hypotheses related to the influencing factors of residents' domestic-waste-sorting behavior from three levels: government, society and individuals. Second, the study designed a questionnaire from five perspectives: individual characteristic variables, government, society, residents and classification behavior. Then, SPSS software was used to carry out descriptive statistical, reliability and validity assessments using ANOVA, correlation and regression analyses on the sample data obtained from the questionnaire. The results suggested that the research hypotheses were statistically significant: (1) females and residents with higher education were more likely to participate in domestic waste classification; (2) reward and punishment measures had the most significant impact on residents' waste-classification behavior; and (3) publicity and education, classification standards, classification facilities, the recycling system, subjective norms, environmental knowledge and environmental attitudes all had a positive effect on residents' household waste classification. Finally, based on the results of the empirical analysis, this paper provides reference suggestions for the further development of domestic waste classification in Shanghai.

Mussel-inspired polyethylene glycol coating for constructing antifouling membrane for water purification.

HYPOTHESIS: Polyethylene glycol (PEG) holds considerable potential in the fabrication of antifouling surfaces due to its strong hydration property. However, anchoring PEG polymer as a stable surface coating is still challenging because of its weak surface bonding property. Inspired by the mussel adhesion strategy, it is hypothesized that PEG polymer can be robustly attached onto substrates with the assistance of a "bio-glue" layer. EXPERIMENTS: The "bio-glue" layer composited of Levodopa/polyethyleneimine (LP) is firstly deposited onto substrates, followed by covalently anchoring the poly(ethylene glycol) diglycidyl ether (PEGDE) layer via ring-opening reaction. The antifouling property of as-prepared coating was characterized using several techniques including quartz crystal microbalance (QCM) and surface forces apparatus (SFA). Furthermore, the PEGDE/LP coating was applied in membrane functionalization for oil-in-water (O/W) emulsion separation. FINDINGS: PEGDE/LP coating shows outstanding stability and superior antifouling properties towards various potential foulants. In the O/W emulsion separation process, the PEGDE/LP-coated membrane maintains its super-hydrophilic property under harsh solution conditions and achieves high water flux (∼3000 L m-2 h-1 bar-1) and 90% water flux recovery ratio for separation of O/W emulsions containing different bio-foulants. This coating strategy provides a promising approach for fabricating stable coating with outstanding antifouling properties in various environmental engineering applications.

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation.

Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.

The chromatin-remodeling enzyme Smarca5 regulates erythrocyte aggregation via Keap1-Nrf2 signaling.

Although thrombosis has been extensively studied using various animal models, our understanding of the underlying mechanism remains elusive. Here, using zebrafish model, we demonstrated that smarca5-deficient red blood cells (RBCs) formed blood clots in the caudal vein plexus. We further used the anti-thrombosis drugs to treat smarca5zko1049a embryos and found that a thrombin inhibitor, argatroban, partially prevented blood clot formation in smarca5zko1049a. To explore the regulatory mechanism of smarca5 in RBC homeostasis, we profiled the chromatin accessibility landscape and transcriptome features in RBCs from smarca5zko1049a and their siblings and found that both the chromatin accessibility at the keap1a promoter and expression of keap1a were decreased. Keap1 is a suppressor protein of Nrf2, which is a major regulator of oxidative responses. We further identified that the expression of hmox1a, a downstream target of Keap1-Nrf2 signaling pathway, was markedly increased upon smarca5 deletion. Importantly, overexpression of keap1a or knockdown of hmox1a partially rescued the blood clot formation, suggesting that the disrupted Keap1-Nrf2 signaling is responsible for the RBC aggregation in smarca5 mutants. Together, our study using zebrafish smarca5 mutants characterizes a novel role for smarca5 in RBC aggregation, which may provide a new venous thrombosis animal model to support drug screening and pre-clinical therapeutic assessments to treat thrombosis.

After an injury, cells in our blood (called red blood cells) often stick together to form clots to stop us from bleeding and prevent infection. These clots, however, can sometimes develop in veins and arteries, resulting in a condition known as thrombosis. If left untreated, these blockages can be life-threatening and lead to a heart attack or stroke. To study the physical effects of venous thrombosis and test different treatments, researchers often use animal models. In particular, the transparent embryos of zebrafish, as it easy to see how blood flows through their circulatory system. However, it is difficult to explore the underlying mechanisms that cause red blood cells to aggregate together using these models. To overcome this, Ding et al. developed a new model for venous thrombosis by deleting the gene for a protein called Smarca5. They found that red blood cells lacking this gene were more likely to clump together in the veins of zebrafish. Further experiments showed that this mutation reduced the activity of the gene for a protein called Keap1a, which suppresses the activity of Nrf2. Nrf2 switches on a number of genes involved in blood clotting, including the gene for the protein Hmox1a. Ding et al. discovered that increasing the activity of the gene that encodes the Keap1a protein, or decreasing the activity of the gene for Hmox1a, partially stopped red blood cells from sticking together in the zebrafish model. These findings suggest that the blood clots formed in the zebrafish model are due to the disrupted connection between Keap1a and Nrf2. This model could be used to screen new drugs for treating venous thrombosis. However, further experiments are still needed to see how similar the blood clots in the zebrafish are to the ones found in patients with this disease.

Does the Employability Paradox Exist or Not? An Inverted U-Shaped Model.

This paper's purpose is to test the employability paradox by adopting a combined linear and non-linear approach based on the conservation of resource (COR) theory and the prospect theory and further to discuss it in two groups of employees with different seniority following the career timetable perspective. A total of 623 pairs of matched employee and manager surveys was collected from 27 Chinese enterprises in two waves. Hierarchical regression analysis was used to test the hypotheses. The results show no paradox that perceived employability promotes both an employee's turnover intention and performance. Specifically, perceived employability has a significant inverted U-shaped effect on turnover intention but no direct influence on job performance. Seniority is a moderator, showing the curvilinear relationship only exhibits for employees with shorter work seniority (≤3 years), and a positive linear relationship between perceived employability and job performance only exists for employees with longer seniority (>3 years). This study emphasizes the value of employability for employers and proposes who is more suitable and what timetable should be followed for employability enhancement in practice. In addition, the study provides an enlightening finding of the inverted U-shaped relationship between perceived employability and turnover intention, applies the COR theory and the prospect theory to explain the non-linear relationship, validates the effect of too much of a good thing (TMGT), and negates the paradox from the perspective of the perceived general employability and career timetable.