Search

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

Thioredoxin reductase (TXNRD) is a selenoprotein that plays a crucial role in cellular antioxidant defense. Previously, a distinctive guiding bar motif was identified in TXNRD1, which influences the transfer of electrons. In this study, utilizing single amino acid substitution and Excitation-Emission Matrix (EEM) fluorescence spectrum analysis, we discovered that the guiding bar communicates with the FAD and modulates the electron flow of the enzyme. Differential Scanning Fluorimetry (DSF) analysis demonstrated that the aromatic amino acid in guiding bar is a stabilizer for TXNRD1. Kinetic analysis revealed that the guiding bar is vital for the disulfide reductase activity but hinders the selenocysteine-independent reduction activity of TXNRD1. Meanwhile, the guiding bar shields the selenocysteine residue of TXNRD1 from the attack of electrophilic reagents. We also found that the inhibition of TXNRD1 by caveolin-1 scaffolding domain (CSD) peptides and compound LCS3 did not bind to the guiding bar motif. In summary, the obtained results highlight new aspects of the guiding bar that restrict the flexibility of the C-terminal redox motif and govern the transition from antioxidant to pro-oxidant.

For a long time, cardiovascular clinicians have focused their research on coronary atherosclerotic cardiovascular disease and acute myocardial infarction due to their high morbidity, high mortality, high disability rate, and limited treatment options. Despite the continuous optimization of the therapeutic methods and pharmacological therapies for myocardial ischemia–reperfusion, the incidence rate of heart failure continues to increase year by year. This situation is speculated to be caused by the current therapies, such as reperfusion therapy after ischemic injury, drugs, rehabilitation, and other traditional treatments, that do not directly target the infarcted myocardium. Consequently, these therapies cannot fundamentally solve the problems of myocardial pathological remodeling and the reduction of cardiac function after myocardial infarction, allowing for the progression of heart failure after myocardial infarction. Coupled with the decline in mortality caused by acute myocardial infarction in recent years, this combination leads to an increase in the incidence of heart failure. As a new promising therapy rising at the beginning of the twenty-first century, cardiac regenerative medicine provides a new choice and hope for the recovery of cardiac function and the prevention and treatment of heart failure after myocardial infarction. In the past two decades, regeneration engineering researchers have explored and summarized the elements, such as cells, scaffolds, and cytokines, required for myocardial regeneration from all aspects and various levels day and night, paving the way for our later scholars to carry out relevant research and also putting forward the current problems and directions for us. Here, we describe the advantages and challenges of cardiac tissue engineering, a contemporary innovative therapy after myocardial infarction, to provide a reference for clinical treatment.

2,2′-Dibromobisphenol A (2,2′-DiBBPA) is frequently detected in the environment. However, the mobility of 2,2′-DiBBPA in the soil environment is poorly understood. The present study examined the effects of soil components such as the NaClO-resistant fraction, dithionite-citrate-bicarbonate -demineralized fraction, humin fraction, black carbon, DOC-removed fraction, exogenous dissolved organic carbon and heavy metal cations on the adsorption of 2,2′-DiBBPA on several types of agricultural soils. The adsorption isotherms on soils and soil components were well fitted to the linear isotherm equation. 2,2′-DiBBPA sorption onto soils was dominated by soil organic matter content (SOM) and affected by exogenous dissolved organic carbon. Linear regression relationships between adsorption capacity (Kd) and soil characteristics were evaluated to predict partitioning of 2,2′-DiBBPA. Black carbon played a predominant role in the adsorption of 2,2′-DiBBPA. Heavy metal ions significantly inhibited the adsorptive behavior of 2,2′-DiBBPA under alkaline conditions. Semiempirical linear relationships were observed between biota-sediment accumulation factors (1.18–2.47)/logarithm of bioconcentration factors (BCFs, 2.49–2.52) of 2,2′-DiBBPA in lugworms and Kd. These results allow for the prediction of the bioaccumulation of 2,2′-DiBBPA in other soils. Furthermore, values of log BCF > 1.0 indicate the preferential bioaccumulation of 2,2′-DiBBPA in biota. These data are of significance for understanding the migration of 2,2′-DiBBPA in agricultural soils and bioaccumulation in organisms.

Abstract The interaction between the aluminum salt-based adjuvants and the antigen in the vaccine formulation is one of the determining factors affecting the immuno-potentiation effect of vaccines. However, it is not clear how the intrinsic properties of the adjuvants could affect this interaction, which limits to benefit the improvement of existing adjuvants and further formulation of new vaccines. Here, we engineered aluminum oxyhydroxide (AlOOH) nanorods and used a variety of antigens including hepatitis B surface antigen (HBsAg), SARS-CoV-2 spike protein receptor-binding domain (RBD), bovine serum albumin (BSA) and ovalbumin (OVA) to identify the key physicochemical properties of adjuvant that determine the antigen adsorption at the nano-bio interface between selected antigen and AlOOH nanorod adjuvant. By using various physicochemical and biophysical characterization methods, it was demonstrated that the surface hydroxyl contents of AlOOH nanorods affected the adsorptive strength of the antigen and their specific surface area determined the adsorptive capacity of the antigen. In addition, surface hydroxyl contents had an impact on the stability of the adsorbed antigen. By engineering the key intrinsic characteristics of aluminum-based adjuvants, the antigen adsorption behavior with the aluminum adjuvant could be regulated. This will facilitate the design of vaccine formulations to optimize the adsorption and stability of the antigen in vaccine.

Targeting thioredoxin reductase (TXNRD) with low-weight molecules is emerging as a high-efficacy anti-cancer strategy in chemotherapy. Sanguinarine has been reported to inhibit the activity of TXNRD1, indicating that benzophenanthridine alkaloid is a fascinating chemical entity in the field of TXNRD1 inhibitors. In this study, the inhibition of three benzophenanthridine alkaloids, including chelerythrine, sanguinarine, and nitidine, on recombinant TXNRD1 was investigated, and their anti-cancer mechanisms were revealed using three gastric cancer cell lines. Chelerythrine and sanguinarine are more potent inhibitors of TXNRD1 than nitidine, and the inhibitory effects take place in a dose- and time-dependent manner. Site-directed mutagenesis of TXNRD1 and in vitro inhibition analysis proved that chelerythrine or sanguinarine is primarily bound to the Sec498 residue of the enzyme, but the neighboring Cys497 and remaining N-terminal redox-active cysteines could also be modified after the conjugation of Sec498. With high similarity to sanguinarine, chelerythrine exhibited cytotoxic effects on multiple gastric cancer cell lines and suppressed the proliferation of tumor spheroids derived from NCI-N87 cells. Chelerythrine elevated cellular levels of reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress. Moreover, the ROS induced by chelerythrine could be completely suppressed by the addition of N-acetyl-L-cysteine (NAC), and the same is true for sanguinarine. Notably, Nec-1, an RIPK1 inhibitor, rescued the chelerythrine-induced rapid cell death, indicating that chelerythrine triggers necroptosis in gastric cancer cells. Taken together, this study demonstrates that chelerythrine is a novel inhibitor of TXNRD1 by targeting Sec498 and possessing high anti-tumor properties on multiple gastric cancer cell lines by eliciting necroptosis.

The stimulator of interferon genes (STING) protein is an important and promising innate immune target for tumor therapy. However, the instability of the agonists of STING and their tendency to cause systemic immune activation is a hurdle. The STING activator, cyclic di-adenosine monophosphate (CDA), produced by the modified Escherichia coli Nissle 1917, shows high antitumor activity and effectively reduces the systemic effects of the “off-target” caused by the activation of the STING pathway. In this study, we used synthetic biological approaches to optimize the translation levels of the diadenylate cyclase that catalyzes CDA synthesis in vitro. We developed 2 engineered strains, CIBT4523 and CIBT4712, for producing high levels of CDA while keeping their concentrations within a range that did not compromise the growth. Although CIBT4712 exhibited stronger induction of the STING pathway corresponding to in vitro CDA levels, it had lower antitumor activity than CIBT4523 in an allograft tumor model, which might be related to the stability of the surviving bacteria in the tumor tissue. CIBT4523 exhibited complete tumor regression, prolonged survival of mice, and rejection of rechallenged tumors, thus, offering new possibilities for more effective tumor therapy. We showed that the appropriate production of CDA in engineered bacterial strains is essential for balancing antitumor efficacy and self-toxicity.

A robust misfit function is essential for mitigating cycle-skipping in full-waveform inversion (FWI), leading to stable updates of the velocity model in this highly nonlinear optimization process. State-of-the-art misfit functions, including matching filter or optimal transport misfits, are all hand-crafted and developed from first principles. With the growth of artificial intelligence in geoscience, we propose learning a robust misfit function for FWI, entitled ML-misfit, based on machine learning. Inspired by the recently introduced optimal transport of the matching filter objective function, we design a specific neural network architecture for the misfit function in a form that allows for global comparison of the predicted and measured data. The proposed neural network architecture also guarantees that the resulting misfit is a pseudo-metric for efficient training. In the framework of meta-learning, we train the network by running FWI to invert for randomly generated velocity models and update the parameters of the neural network by minimizing the meta-loss, which is defined as the accumulated difference between the true and inverted velocity models. The learning and improvement of such an ML-misfit are automatic, and the resulting ML-misfit is data-adaptive. We first illustrate the basic principles behind the ML-misfit for learning a convex misfit function using a travel-time shifted signal example. Furthermore, we train the neural network on 2D horizontally layered models and apply the trained neural network to the Marmousi model; the resulting ML-misfit provides robust updating of the model and mitigates the cycle-skipping issue successfully.

Summary: The freezing-induced aggregation of aluminum-based (Alum) adjuvants has been considered as the most important cause of reduced vaccine potency. However, the intrinsic properties that determine the functionality of Alum after freezing have not been elucidated. In this study, we used engineered aluminum oxyhydroxide nanoparticles (AlOOH NPs) and demonstrated that cryogenic freezing led to the mechanical pressure-mediated reduction of surface hydroxyl. The sugar-based surfactant, octyl glucoside (OG), was demonstrated to shield AlOOH NPs from the freezing-induced loss of hydroxyl content and the aggregation through the reduction of recrystallization-induced mechanical stress. As a result, the antigenic adsorption property of frozen AlOOH NPs could be effectively protected. When hepatitis B surface antigen (HBsAg) was adjuvanted with OG-protected frozen AlOOH NPs in mice, the loss of immunogenicity was inhibited. These findings provide insights into the freezing-induced surface decomposition of Alum and can be translated to design of protectants to improve the stability of vaccines.

The development of oil and gas pipelines is booming in China. This is not only a great opportunity for pipeline industry, but also a challenge to improve the operation level of pipeline. The intelligent acquisition system of cathodic protection potential is an efficient tool to monitor and inspect the cathodic protection, which consists of a buried probe, a terminal acquisition instrument and a software system. Currently, the system has been used in the major pipeline companies of China to implement the remote monitoring of cathodic protection parameters in real time. However, there are such problems as high failure rate, low compatibility of the data management platform and simple algorithm of analysis and evaluation software. In this study, the development of the intelligent acquisition system of cathode protection potential, including the development of hardware and software, and the situation of field application, was reviewed, the problems encountered in application were summarized, and prospect was made in terms of improving the level of standardization, increasing the reliability, solving the hot issues and aiding the construction of intelligent pipelines. Subsequently, more efforts should be made in the study of the reliability and standardization of the acquisition system and the fields of application should be expanded, so as to provide technical support to the construction of intelligent pipelines.

Pseudo-semi interpenetrating polymer networks (pseudo-semi IPNs) are a special example of topological isomerism in macromolecules, which have attracted significant attention in recent years with a high potential in a variety of engineering applications of polymeric materials. In this article, pseudo-semi IPNs were synthetized by sequential polymerization of thermoplastic polymers (TPEs) in the presence of thermosetting elastomer (TSEs) with contents of 10, 20, 30, 40 and 50 wt.% in a vacuum oven at 60 °C for about 72 h. In addition, this article describes a method for researching the elastic modulus, effective crosslinking density and physical crosslinking density of TSEs and pseudo-semi IPNs. The inherent interactions and entanglements of pseudo-semi IPNs were discussed by analyzing the changes in elastic modulus and effective crosslinking density at different temperatures. The results show that after the TPE was added to the TSE matrix as a plastic-reinforced material, the ductility increased from 89.6% to 491%, the effective crosslinking density was increased by 100% at high temperatures and the strength of the material matrix was significantly improved. Two physical events take place in our pseudo-semi IPNs as result of energy dissipation and polymeric chains mobility.

In response to the issue of virus contamination in the cold-chain warehouse or hospital environment under the influence of the COVID-19, we propose the design work of a disinfection robot based on the UVC radiation mechanism using the low-computational path optimization at-the-edge. To build a surface disinfection robot with less computing power to generate a collision-free path with shorter total distance in studies, a 2D map is used as a graph-based approach to automatically generate a closed-loop disinfection path to cover all the accessible surfaces. The discrete disinfection points from the map are extracted with effective disinfection distances and sorted by a nearest-neighbor (NN) search over historical trajectory data and improved A * algorithm to obtain an efficient coverage path to all accessible boundaries of the entire area. The purpose of improved A * algorithm with NN is not to find the optimal path solution but to optimize one with reasonable computing power. The proposed algorithm enhances the path-finding efficiency by a dynamically weighted heuristic function and reduces the path turning angles, which improves the path smoothness significantly requiring less computing power. The Gazebo simulation is conducted, and the prototype disinfection robot has been built and tested in a real lab environment. Compared with the classic A * algorithm, the improved A * algorithm with NN has improved the path-finding efficiency and reduced the path length while covering the same area. Both the simulation and experimental results show that this approach can provide the design to balance the tradeoffs among the path-finding efficiency, smoothness, disinfection coverage, and computation resources.

Mo2FeB2-based cermets have wide applications in fields of wear resistance, corrosion resistance and heat resistance due to their simple preparation process, low-cost raw materials, and prominent mechanical properties. Herein, Mo2FeB2-based cermets with xMo (x = 43.5, 45.5, 47.5, 49.5, wt.%) were prepared by means of the vacuum liquid phase sintering technique. Investigations on the microstructure and mechanical properties of Mo2FeB2-based cermets with Mo addition were performed. Experimental results show that, with Mo content increasing, the average particle size decreases gradually, revealing that the grain coarsening of Mo2FeB2-based cermets is controlled by interface reaction. In addition, Mo2FeB2 grains gradually transform from an elongated shape to a nearly equiaxed shape. The improvement of Mo2FeB2 hard phase on the morphology is mainly due to the inhibition of solution–precipitation reaction by increasing Mo. Furthermore, the relative density of cermets decreases due to the reduced Fe content. When Mo content is 47.5 wt.%, a relatively small grain size of Mo2FeB2 is obtained (about 2.03 μm). Moreover, with the increase in Mo content, hardness and transverse rupture strength (TRS) of Mo2FeB2-based cermets increase firstly and then decrease. Whereas, with increasing Mo content, the fracture toughness deteriorates gradually. When Mo content is 47.5 wt.%, the comprehensive mechanical properties of cermets are the best. The optimal raw material ratio for the preparation of Mo2FeB2-based cermets in this study is determined to be 47.5 wt.% Mo–6.0 wt.% B-Fe.

This study describes a quencher-free fluorescent aptasensor for ochratoxin A (OTA) detection using the specific quenching ability of guanine for fluorescein (FAM) molecules based on photo-induced electron transfer (PIET). In this strategy, OTA is detected by monitoring the fluorescence change induced by the conformational change of the aptamer after target binding. A new shorter OTA aptamer compromising three guanine bases at the 5′ end was used in this study. This new aptamer, named G3-OTAapt1-FAM (F1), was labeled with FAM on the 3′ end as a fluorophore. In order to increase the binding affinity of the aptamer and OTA, G3-OTAapt2-FAM (F2) was designed; this added a pair of complementary bases at the end compared with F1. To prevent the strong self-quenching of F2, a complementary chain, A13, was added. Although the F1 aptasensor was simpler to implement, the sensitivity of the F2 aptasensor with A13 was better than that of F1. The proposed F1 and F2 sensors can detect OTA with a concentration as low as 0.69 nmol/L and 0.36 nmol/L, respectively.

Vaccine development utilizing various platforms is one of the strategies that has been proposed to address the coronavirus disease 2019 (COVID-19) pandemic. Adjuvants are critical components of both subunit and certain inactivated vaccines because they induce specific immune responses that are more robust and long-lasting. A review of the history of coronavirus vaccine development demonstrates that only a few adjuvants, including aluminum salts, emulsions, and TLR agonists, have been formulated for the severe acute respiratory syndrome-associated coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and currently the SARS-CoV-2 vaccines in experimental and pre-clinical studies. However, there is still a lack of evidence regarding the effects of the adjuvants tested in coronavirus vaccines. This paper presents an overview of adjuvants that have been formulated in reported coronavirus vaccine studies, which should assist with the design and selection of adjuvants with optimal efficacy and safety profiles for COVID-19 vaccines.

ABSTRACT Colistin is used as the “last resort” to treat infections caused by multidrug-resistant Acinetobacter baumannii, which is at the top of the World Health Organization’s list of the most dangerous bacterial species that threaten human health. Unfortunately, colistin resistance has emerged in A. baumannii. To broaden the study of the resistance mechanism of colistin in A. baumannii, we obtained colistin-resistant mutants via two methods: (i) screening and isolation from a mariner-based A. baumannii ATCC 19606 transposon mutant library; (ii) selection from challenge of ATCC 19606 with successively increasing concentrations of colistin. A total of 41 mutants with colistin MIC of 4 μg/ml to 64 μg/ml were obtained by transposon mutant library screening. Five highly resistant mutants with colistin MICs ranging from 256 μg/ml to 512 μg/ml were selected from successive colistin challenges. Genotypic complementation and remodeling of the transposon mutants revealed that the genes inactivated by the transposon insertion were not responsible for resistance. Whole-genome sequence analysis of the colistin-resistant strains revealed that the main causes of the resistance to colistin were mutations in the pmrA-pmrB genes, including pmrAP102R, pmrBP233S, and pmrBT235N and the novel alleles pmrAI13M and pmrBQ270P. Interestingly, we found that miaAI221V mutation of A. baumannii strain ATCC 19606 (pmrAP102R) resulted in 4-fold increases in the colistin MIC, which rose from 32 μg/ml to 128 μg/ml. But miaAI221V itself had little effect on the colistin susceptibility of ATCC 19606. These data broaden knowledge of the scope of chromosomally encoded mechanisms of resistance to colistin. IMPORTANCE Acinetobacter baumannii is an important Gram-negative opportunistic pathogen commonly infecting critically ill patients. It possesses a remarkable ability to survive in the hospital environment and acquires resistance determinants corresponding to a wide range of antibacterial agents. Given that the current treatment options for multidrug resistant A. baumannii are extremely limited, colistin administration has become the treatment of last resort. However, colistin-resistant A. baumannii strains have recently been reported. The mechanism of resistance to colistin in A. baumannii has rarely been reported. Here, we found two novel mutations in pmrA (I13M) and pmrB (Q270P) that caused colistin resistance. It is also first reported here that the presence of miaA with a I221V mutation enhanced the colistin resistance of pmrAP102R.

Pancreatic cancer remains difficult to treat mainly due to the drug delivery challenges posed by a strong stromal component. Here the authors develop nanocarriers that improve drug delivery efficiency and engage the host immune system against the tumor resulting in reduction of tumor growth and metastasis.

As an essential electrolyte for the human body, the potassium ion (K+) plays many physiological roles in living cells, so the rapid and accurate determination of serum K+ is of great significance. In this work, we developed a solid-contact ion-selective electrode (SC-ISE) using MoS2/Fe3O4 composites as the ion-to-electron transducer to determine serum K+. The potential response measurement of MoS2/Fe3O4/K+-ISE shows a Nernst response by a slope of 55.2 ± 0.1 mV/decade and a low detection limit of 6.3 × 10−6 M. The proposed electrode exhibits outstanding resistance to the interference of O2, CO2, light, and water layer formation. Remarkably, it also presents a high performance in potential reproducibility and long-term stability.

Corynebacterium glutamicum is an important industrial microbe, however it has proven difficult to genetically engineer using Cas9 from Streptococcus pyogenes. Here the authors report effective genome engineering of the bacterium using Cpf1 from Francisella novicida.

[This corrects the article DOI: 10.1371/journal.pone.0154447.].

In this study, we have generated and characterized Electronic Cigarette (EC) aerosols using a combination of advanced technologies. In the gas phase, the particle number concentration (PNC) of EC aerosols was found to be positively correlated with puff duration whereas the PNC and size distribution may vary with different flavors and nicotine strength. In the liquid phase (water or cell culture media), the size of EC nanoparticles appeared to be significantly larger than those in the gas phase, which might be due to aggregation of nanoparticles in the liquid phase. By using in vitro high-throughput cytotoxicity assays, we have demonstrated that EC aerosols significantly decrease intracellular levels of glutathione in NHOKs in a dose-dependent fashion resulting in cytotoxicity. These findings suggest that EC aerosols cause cytotoxicity to oral epithelial cells in vitro, and the underlying molecular mechanisms may be or at least partially due to oxidative stress induced by toxic substances (e.g., nanoparticles and chemicals) present in EC aerosols.