Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.

Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.

Temperature-Dependent Electrochemical Performance of Ta-Substituted SrCoO3 Perovskite for Supercapacitors.

Developing new electrode materials with good temperature-dependent electrochemical performance has become a great issue for the deployment of hybrid supercapacitors with wide temperature tolerance. In this work, a series of Ta-substituted SrCo1-x Tax O3-δ (x=0.05, 0.10, 0.15, 0.20) perovskites have been studied as positive electrodes for hybrid supercapacitors in terms of their structures, elemental valence states and electrochemical performances. Incorporating Ta into SrCoO3-δ perovskite not only stabilizes the crystallite structure but also notably improves electrochemical activities. The SrCo0.95 Ta0.05 O3-δ @CC delivers the highest specific capacity (Qsp ) of 227.91 C g-1 at 1 A g-1 , which is attributed to the highest oxygen vacancy content and the fastest oxygen diffusion kinetics. The hybrid supercapacitor SrCo0.95 Ta0.05 O3-δ @CC//AC@CC exhibits a high energy density of 22.82 Wh kg-1 @775.09 W kg-1 and a stable long-term cycle life (5000 cycles) with 90.7 % capacity retention. As temperature increases from 25 to 85 °C, the capacitance properties are improved at elevated temperatures for both electrode and device due to the increased electrolyte conductivity. The outstanding electrochemical results present that SrCo1-x Tax O3-δ perovskite holds good prospects for hybrid supercapacitors with wide temperature tolerance.

DeepKa Web Server: High-Throughput Protein pKa Prediction.

DeepKa is a deep-learning-based protein pKa predictor proposed in our previous work. In this study, a web server was developed that enables online protein pKa prediction driven by DeepKa. The web server provides a user-friendly interface where a single step of entering a valid PDB code or uploading a PDB format file is required to submit a job. Two case studies have been attached in order to explain how pKa's calculated by the web server could be utilized by users. Finally, combining the web server with post processing as described in case studies, this work suggests a quick workflow of investigating the relationship between protein structure and function that are pH dependent. The web server of DeepKa is freely available at http://www.computbiophys.com/DeepKa/main.

Development of a Method for Soil Tilth Quality Evaluation from Crumbling Roller Baskets Using Deep Machine Learning Models.

A combination tillage with disks, rippers, and roller baskets allows the loosening of compacted soils and the crumbling of soil clods. Statistical methods for evaluating the soil tilth quality of combination tillage are limited. Light Detection and Ranging (LiDAR) data and machine learning models (Random Forest (RF), Support Vector Machine (SVM), and Neural Network (NN)) are proposed to investigate roller basket pressure settings on soil tilth quality. Soil profiles were measured using LiDAR (stop and go and on-the-go) and RGB visual images from a Completely Randomized Design (CRD) tillage experiment on clay loam soil with treatments of roller basket down, roller basket up, and no-till in three replicates. Utilizing RF, SVM, and NN methods on the LiDAR data set identified median, mean, maximum, and standard deviation as the top features of importance variables that were statistically affected by the roller settings. Applying multivariate discriminatory analysis on the four statistical measures, three soil tilth classes were predicted with mean prediction rates of 77% (Roller-basket down), 64% (Roller-basket up), and 90% (No till). The LiDAR data analytics-inspired soil tilth classes correlated well with the RGB image discriminatory analysis. Soil tilth machine learning models were shown to be successful in classifying soil tilth with regard to onboard operator pressure control settings on the roller basket of the combination tillage implement.

A Droplet Method for Synthesis of Multiclass Ultrathin Metal Halides.

2D metal halides have attracted increasing research attention in recent years; however, it is still challenging to synthesize them via liquid-phase methods. Here it is demonstrated that a droplet method is simple and efficient for the synthesis of multiclass 2D metal halides, including trivalent (BiI3 , SbI3 ), divalent (SnI2 , GeI2 ), and monovalent (CuI) ones. In particular, 2D SbI3 is first experimentally achieved, of which the thinnest thickness is ≈6 nm. The nucleation and growth of these metal halide nanosheets are mainly determined by the supersaturation of precursor solutions that are dynamically varying during the solution evaporation. After solution drying, the nanosheets can fall on the surface of many different substrates, which further enables the feasible fabrication of related heterostructures and devices. With SbI3 /WSe2 being a good demonstration, the photoluminescence intensity and photo responsivity of WSe2 is obviously enhanced after interfacing with SbI3 . The work opens a new pathway for 2D metal halides toward widespread investigation and applications.

Dynamics of cutaneous atmospheric oxygen uptake in response to mechanical stretch revealed by optical fiber microsensor.

Skin expands and regenerates in response to mechanical stretch. This important homeostasis process is critical for skin biology and can be exploited to generate extra skin for reconstructive surgery. Atmospheric oxygen uptake is important in skin homeostasis. However, whether and how cutaneous atmospheric oxygen uptake changes during mechanical stretch remains unclear, and relevant research tools to quantify oxygen flux are limited. Herein, we used the scanning micro-optrode technique (SMOT), a non-invasive self-referencing optical fiber microsensor, to achieve real-time measurement of cutaneous oxygen uptake from the atmosphere. An in vivo mechanical stretch-induced skin expansion model was established, and an in vitro Flexcell Tension system was used to stretch epidermal cells. We found that oxygen influx of skin increased dramatically after stretching for 1 to 3 days and decreased to the non-stretched level after 7 days. The enhanced oxygen influx of stretched skin was associated with increased epidermal basal cell proliferation and impaired epidermal barrier. In conclusion, mechanical stretch increases cutaneous oxygen uptake with spatial-temporal characteristics, correlating with cell proliferation and barrier changes, suggesting a fundamental mechanistic role of oxygen uptake in the skin in response to mechanical stretch. Optical fiber microsensor-based oxygen uptake detection provides a non-invasive approach to understand skin homeostasis.

Basis for Accurate Protein pKa Prediction with Machine Learning.

pH regulates protein structures and the associated functions in many biological processes via protonation and deprotonation of ionizable side chains where the titration equilibria are determined by pKa's. To accelerate pH-dependent molecular mechanism research in the life sciences or industrial protein and drug designs, fast and accurate pKa prediction is crucial. Here we present a theoretical pKa data set PHMD549, which was successfully applied to four distinct machine learning methods, including DeepKa, which was proposed in our previous work. To reach a valid comparison, EXP67S was selected as the test set. Encouragingly, DeepKa was improved significantly and outperforms other state-of-the-art methods, except for the constant-pH molecular dynamics, which was utilized to create PHMD549. More importantly, DeepKa reproduced experimental pKa orders of acidic dyads in five enzyme catalytic sites. Apart from structural proteins, DeepKa was found applicable to intrinsically disordered peptides. Further, in combination with solvent exposures, it is revealed that DeepKa offers the most accurate prediction under the challenging circumstance that hydrogen bonding or salt bridge interaction is partly compensated by desolvation for a buried side chain. Finally, our benchmark data qualify PHMD549 and EXP67S as the basis for future developments of protein pKa prediction tools driven by artificial intelligence. In addition, DeepKa built on PHMD549 has been proven an efficient protein pKa predictor and thus can be applied immediately to, for example, pKa database construction, protein design, drug discovery, and so on.

C3-Selective Trifluoromethylthiolation and Difluoromethylthiolation of Pyridines and Pyridine Drugs via Dihydropyridine Intermediates.

Herein, we report a method for C3-selective C-H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to form functionalized dihydropyridines, which then undergo oxidative aromatization. The method can be used for late-stage functionalization of pyridine drugs for the generation of new drug candidates.

Borane-Catalyzed C3-Alkylation of Pyridines with Imines, Aldehydes, or Ketones as Electrophiles.

Achieving C3-selective pyridine functionalization is a longstanding challenge in organic chemistry. The existing methods, including electrophilic aromatic substitution and C-H activation, often require harsh reaction conditions and excess pyridine and generate multiple regioisomers. Herein, we report a method for borane-catalyzed tandem reactions that result in exclusively C3-selective alkylation of pyridines. These tandem reactions consist of pyridine hydroboration, nucleophilic addition of the resulting dihydropyridine to an imine, an aldehyde, or a ketone, and subsequent oxidative aromatization. Because the pyridine is the limiting reactant and the reaction conditions are mild, this method constitutes a practical tool for late-stage functionalization of structurally complex pharmaceuticals bearing a pyridine moiety.

Humidity-Responsive Guar Gum Fibers by Wet Spinning.

In this study, guar gum fibers were obtained by wet spinning, in which epichlorohydrin (ECH) and calcium chloride (CaCl2) were used as the cross-linking agent and metal complexing agent, respectively. The fibers' chemical structure, morphology, crystallinity, and thermal and mechanical properties were analyzed by Fourier infrared spectroscopy, scanning electron microscopy, and so forth. The results showed that ECH reacted with guar gum and formed ether bonds. Meanwhile, ECH can effectively increase the number of cross-linking points and improve the mechanical properties of the fibers. When the ECH content was 12% (w/w), the breaking strength could reach 2.4 cN/dtex. The conductivity of MC-GG fibers varied with the relative humidity and could reach 2.845 × 10-2 S/cm at maximum. Meanwhile, the contact angle of MC-GG fibers was 33°, indicating that the fibers had good hydrophilicity and humidity response ability and had excellent potential in the field of smart fabrics.

Transcription factor GlbHLH regulates hyphal growth, stress resistance, and polysaccharide biosynthesis in Ganoderma lucidum.

Basic helix-loop-helix (bHLH) transcription factors (TFs) participate in many physiological and cellular processes in eukaryotes. However, their functions remain unclear in the macro basidiomycete Ganoderma lucidum (G. lucidum). In this study, a gene encoding bHLH TF, GlbHLH, was identified in G. lucidum. The knockdown of GlbHLH by RNA interference reduced hyphal growth, hyphal branching, and resistant to osmotic, oxidative, and cell wall stress. The content of cell wall components ß-1,3 glucan and chitin and the expression of their synthesis genes were decreased in the GlbHLH knockdown strains. The knockdown of GlbHLH led to an increase of intracellular reactive oxygen species by decreasing the enzyme activity and gene expression of antioxidant enzymes. Furthermore, the production of intracellular polysaccharides and extracellular polysaccharides was greatly decreased in the GlbHLH mutants. These results suggested that GlbHLH is involved in hyphal growth, stress response, and polysaccharide biosynthesis in G. lucidum.

High-Efficiency and High-Quality Extraction of Hemicellulose of Bamboo by Freeze-Thaw Assisted Two-Step Alkali Treatment.

Hemicellulose is a major component of the complex biomass recalcitrance structure of fiber cell walls. Even though biomass recalcitrance protects plants, it affects the effective utilization of lignocellulosic biomass resources. Therefore, the separation and extraction of hemicellulose is very important. In this study, an improved two-step alkali pretreatment method was proposed to separate hemicellulose efficiently. Firstly, 16.61% hemicellulose was extracted from bamboo by the weak alkali treatment. Then, the physical freezing and the alkali treatment were carried out by freezing at -20 °C for 12.0 h and thawing at room temperature, heating to 80 °C, and treating with 5.0% sodium hydroxide for 90 min; the extraction yield of hemicellulose reached 73.93%. The total extraction yield of the two steps was 90.54%, and the molecular weight and purity reached 44,865 g·mol-1 and 89.60%, respectively. It provides a new method for breaking the biomass recalcitrance of wood fiber resources and effectively extracting hemicellulose.

Enhanced exopolysaccharide production in submerged fermentation of Ganoderma lucidum by Tween 80 supplementation.

Bioactive polysaccharides extracted from Ganoderma lucidum (G. lucidum) have been widely applied in food and medicine for their multiple functions. In this study, G. lucidum exopolysaccharide (EPS) production in submerged fermentation was stimulated by Tween 80. The addition of 0.25% Tween 80 on day 3 gave a maximum production of mycelial biomass and EPS, with an increase of 19.76 and 137.50%, respectively. Analysis of fermentation kinetics showed that glucose was consumed faster after adding Tween 80, while the expression of EPS biosynthesis-related genes and ATP generation were greatly improved. Moreover, Tween 80 resulted in the significant accumulation of reactive oxygen species and increased cell membrane and cell wall permeability. The EPS from Tween 80-containing medium had higher contents of carbohydrate and uronic acid, lower molecular weight, and higher antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals than those of EPS produced in the absence of Tween 80. This study provides further evidence to clarify the stimulatory effects of Tween 80 in fermentation and provides a guide for the production of bioactive G. lucidum EPS.

Mechanical stretch promotes tumoricidal M1 polarization via the FAK/NF-κB signaling pathway.

Macrophages (Mφs) can be used as a part of cell-based cancer immunotherapy. However, they may be hampered by a failure to effectively and stably regulate their polarization state to enhance their tumoricidal effects. In this work, mechanical stretch (MS), as a biology-free modulatory method, was shown to enhance M1 polarization and tumoricidal effects. By using an in vitro Flexcell Tension system, we found that murine Mφ RAW264.7 cells showed higher M1 polarization-related mRNA expression and cytokine release after MS. Further molecular analyses found that focal adhesion kinase and NF-κB activation occurred in the MS-induced M1 polarization. Coculture of MS-preconditioned Mφ with B16F10 skin melanoma cells in vitro showed that the proliferation of B16F10 cells decreased, whereas caspase-3-induced apoptosis increased. Importantly, the injection of MS-preconditioned Mφ into murine skin melanomas in vivo impeded tumor growth; lesions were characterized by increased amounts of M1 Mφ, decreased tumor cell proliferation, and increased tumor cell apoptosis in the tumor microenvironment. Together, our results suggest that MS could be used as a simple preconditioning approach to prepare tumoricidal M1 Mφ for cancer immunotherapy.-Shan, S., Fang, B., Zhang, Y., Wang, C., Zhou, J., Niu, C., Gao, Y., Zhao, D., He, J., Wang, J., Zhang, X., Li, Q. Mechanical stretch promotes tumoricidal M1 polarization via the FAK/NF-κB signaling pathway.

Infrared Thermography Measurement for Vibration-Based Structural Health Monitoring in Low-Visibility Harsh Environments.

In this study, infrared thermography is used for vibration-based structural health monitoring (SHM). Heat sources are employed as sensors. An acrylic frame structure was experimentally investigated using the heat sources as structural marker points to record the vibration response. The effectiveness of the infrared thermography measurement system was verified by comparing the results obtained using an infrared thermal imager with those obtained using accelerometers. The average error in natural frequency was between only 0.64% and 3.84%. To guarantee the applicability of the system, this study employed the mode shape curvature method to locate damage on a structure under harsh environments, for instance, in dark, hindered, and hazy conditions. Moreover, we propose the mode shape recombination method (MSRM) to realize large-scale structural measurement. The partial mode shapes of the 3D frame structure are combined using the MSRM to obtain the entire mode shape with a satisfactory model assurance criterion. Experimental results confirmed the feasibility of using heat sources as sensors and indicated that the proposed methods are suitable for overcoming the numerous inherent limitations associated with SHM in harsh or remote environments as well as the limitations associated with the SHM of large-scale structures.

Underwater Hyperspectral Imaging Technology and Its Applications for Detecting and Mapping the Seafloor: A Review.

Common methods of ocean remote sensing and seafloor surveying are mainly carried out by airborne and spaceborne hyperspectral imagers. However, the water column hinders the propagation of sunlight to deeper areas, thus limiting the scope of observation. As an emerging technology, underwater hyperspectral imaging (UHI) is an extension of hyperspectral imaging technology in air conditions, and is undergoing rapid development for applications in shallow and deep-sea environments. It is a close-range, high-resolution approach for detecting and mapping the seafloor. In this paper, we focus on the concepts of UHI technology, covering imaging systems and the correction methods of eliminating the water column's influence. The current applications of UHI, such as deep-sea mineral exploration, benthic habitat mapping, and underwater archaeology, are highlighted to show the potential of this technology. This review can provide an introduction and overview for those working in the field and offer a reference for those searching for literature on UHI technology.

Highly Transparent and Self-Extinguishing Nanofibrillated Cellulose-Monolayer Clay Nanoplatelet Hybrid Films.

A viable solution toward "green" optoelectronics is rooted in our ability to fabricate optoelectronics on transparent nanofibrillated cellulose (NFC) film substrates. However, the flammability of transparent NFC film poses a severe fire hazard in optoelectronic devices. Despite many efforts toward enhancing the fire-retardant features of transparent NFC film, making NFC film fire-retardant while maintaining its high transparency (≥90%) remains an ambitious objective. Herein, we combine NFC with NFC-dispersed monolayer clay nanoplatelets as a fire retardant to prepare highly transparent NFC-monolayer clay nanoplatelet hybrid films with a superb self-extinguishing behavior. Homogeneous and stable monolayer clay nanoplatelet dispersion was initially obtained by using NFC as a green dispersing agent with the assistance of ultrasonication and then used to blend with NFC to prepare highly transparent and self-extinguishing hybrid films by a water evaporation-induced self-assembly process. As the content of monolayer clay nanoplatelets increased from 5 wt % to 50 wt %, the obtained hybrid films presented enhanced self-extinguishing behavior (limiting oxygen index sharply increased from 21% to 96.5%) while retaining a ∼90% transparency at 600 nm. More significantly, the underlying mechanisms for the high transparency and excellent self-extinguishing behavior of these hybrid films with a clay nanoplatelet content of over 30 wt % were unveiled by a series of characterizations such as SEM, XRD, TGA, and limiting oxygen index tester. This work offers an alternative environmentally friendly, self-extinguishing, and highly transparent substrate to next-generation optoelectronics, and is aimed at providing a viable solution to environmental concerns that are caused by ever-increasing electronic waste.

Aspiration of thrombus for intermediate-risk subacute pulmonary embolism.

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543-603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543-603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.

Mechanical stiffness promotes skin fibrosis through FAPα-AKT signaling pathway.

BACKGROUND: Myofibroblasts contribute to the excessive production, remodeling and cross-linking of the extracellular matrix that characterizes the progression of skin fibrosis. An important insight into the pathogenesis of tissue fibrosis has been the discovery that increased matrix stiffness during fibrosis progression is involved in myofibroblast activation. However, mechanistic basis for this phenomenon remains elusive. OBJECTIVE: To explore the role of fibroblast activation protein-α (FAPα) in mechanical stiffness-induced skin fibrosis progression. METHODS: RNA-seq was performed to compare differential genes of mouse dermal fibroblasts (MDFs) grown on low or high stiffness plates. This process identified FAPα, which is a membrane protein usually overexpressed in activated fibroblasts, as a suitable candidate. In vitro assay, we investigate the role of FAPα in mechanical stiffness-induced MDFs activation and downstream pathway. By establishing mouse skin fibrosis model and intradermally administrating FAPα adeno-associated virus (AAV) or a selective Fap inhibitor FAPi, we explore the role of FAPα in skin fibrosis in vivo. RESULTS: We show that FAPα, a membrane protein highly expressed in myofibroblasts of skin fibrotic tissues, is regulated by increased matrix stiffness. Genetic deletion or pharmacological inhibition of FAPα significantly inhibits mechanical stiffness-induced activation of myofibroblasts in vitro. Mechanistically, FAPα promotes myofibroblast activation by stimulating the PI3K-Akt pathway. Furthermore, we showed that administration of the inhibitor FAPi or FAPα targeted knockdown ameliorated the progression of skin fibrosis. CONCLUSION: Taken together, we identify FAPα as an important driver of mechanical stiffness-induced skin fibrosis and a potential therapeutic target for the treatment of skin fibrosis.

Homogeneous to heterogeneous redox mediator enhancing ferrate(VI) oxidation of sulfamethoxazole: Role of ferrate(VI) activation and electron shuttle.

Ferrate (Fe(VI)) is a promising oxidant for water remediation, yet it has limited reactivity towards certain recalcitrant but important emerging contaminants, such as sulfamethoxazole. Here, this study demonstrates that nitroxide redox mediators, specifically 9-azabicyclo[3.3.1]nonasne N-oxyl (ABNO), can catalyze Fe(VI) reaction with sulfamethoxazole by functioning both as Fe(VI) activator and electron shuttle. The underlying mechanism is explained as: (i) Fe(VI) activation: a series of one-electron transfers between Fe(VI) and ABNO produces highly reactive Fe(V)/Fe(IV) and ABNO+; (ii) electron shuttle: the newly formed active ABNO+ reacts with the sulfamethoxazole, contributing to its removal. Concurrently, ABNOH is generated and subsequently converted back to ABNO by reactive species, thereby completing the redox cycle. The as-developed heterogeneous redox mediator, ABNO@SiO2, retained its catalytic properties and effectively catalyzed Fe(VI) to remove sulfamethoxazole at environmentally relevant pH levels.