Extracellular matrix stiffness as an energy metabolism regulator drives osteogenic differentiation in mesenchymal stem cells.

The biophysical factors of biomaterials such as their stiffness regulate stem cell differentiation. Energy metabolism has been revealed an essential role in stem cell lineage commitment. However, whether and how extracellular matrix (ECM) stiffness regulates energy metabolism to determine stem cell differentiation is less known. Here, the study reveals that stiff ECM promotes glycolysis, oxidative phosphorylation, and enhances antioxidant defense system during osteogenic differentiation in MSCs. Stiff ECM increases mitochondrial fusion by enhancing mitofusin 1 and 2 expression and inhibiting the dynamin-related protein 1 activity, which contributes to osteogenesis. Yes-associated protein (YAP) impacts glycolysis, glutamine metabolism, mitochondrial dynamics, and mitochondrial biosynthesis to regulate stiffness-mediated osteogenic differentiation. Furthermore, glycolysis in turn regulates YAP activity through the cytoskeletal tension-mediated deformation of nuclei. Overall, our findings suggest that YAP is an important mechanotransducer to integrate ECM mechanical cues and energy metabolic signaling to affect the fate of MSCs. This offers valuable guidance to improve the scaffold design for bone tissue engineering constructs.

Charge Dispersion Strategy for High-Performance and Rain-Proof Triboelectric Nanogenerator.

Triboelectric nanogenerator (TENG) is becoming a sustainable and renewable way of energy harvesting and self-powered sensing because of low cost, simple structure, and high efficiency. However, the output current of existing TENGs is still low. It is proposed that the output current of TENGs can be dramatically improved if the triboelectric charges can distribute inside the triboelectric layers. Herein, a novel single-electrode conductive network-based TENG (CN-TENG) is developed by introducing a conductive network of multiwalled carbon nanotubes in dielectric triboelectric layer of thermoplastic polyurethane (TPU). In this CN-TENG, the contact electrification-induced charges distribute on both the surface and interior of the dielectric TPU layer. Thus, the short-circuit current of CN-TENG improves for 100-fold, compared with that of traditional dielectric TENG. In addition, this CN-TENG, even without packing, can work stably in high-humidity environments and even in the rain, which is another main challenge for conventional TENGs due to charge leakage. Further, this CN-TENG is applied for the first time, to successfully distinguish conductive and dielectric materials. This work provides a new and effective strategy to fabricate TENGs with high output current and humidity-resistivity, greatly expanding their practical applications in energy harvesting, movement sensing, human-machine interaction, and so on.

Selectively Adsorbed p-Aminothiophenol Molecules Improve the Electrocatalytic and Photo-Electrocatalytic Hydrogen Evolution on Au/TiO2.

Electrocatalytic hydrogen evolution reaction (HER) is receiving increasing attention as an effective process to produce clean energy. The commonly used precious metal catalysts can be hybridized with semiconductors to form heterostructures for the improvement of catalytic efficiency and reduction of cost. It will be promising to further improve the efficiency of heterostructure-based nanocatalysts in electrocatalytic and photocatalytic HER using a simple and effective method. Herein, we improve the efficiency of Au/TiO2 in electrocatalytic and photo-electrocatalytic HER by selectively adsorbing p-aminothiophenol (PATP) molecules. The PATP molecules are adsorbed on the gold surface by using a simple solution-based method and favor the charge separation at the Au-TiO2 interface. We also compare the PATP molecules with other thiophenol molecules in the enhancement of electrocatalytic HER. The PATP-induced enhancement in electrocatalysis is then further investigated by density functional theory (DFT) calculations, and this enhancement is attributed to a reduction in Gibbs energy of adsorbed hydrogen after surface adsorption of PATP molecules. This work provides a simple, cost-effective, and highly efficient approach to improve the electrocatalytic and photo-electrocatalytic efficiency of Au/TiO2, and this approach could be easily extended to other heterostructure-based nanocatalysts for performance enhancement and may be used in many other catalytic reactions.

Multidisciplinary considerations of fairness in medical AI: A scoping review.

INTRODUCTION: Artificial Intelligence (AI) technology has been developed significantly in recent years. The fairness of medical AI is of great concern due to its direct relation to human life and health. This review aims to analyze the existing research literature on fairness in medical AI from the perspectives of computer science, medical science, and social science (including law and ethics). The objective of the review is to examine the similarities and differences in the understanding of fairness, explore influencing factors, and investigate potential measures to implement fairness in medical AI across English and Chinese literature. METHODS: This study employed a scoping review methodology and selected the following databases: Web of Science, MEDLINE, Pubmed, OVID, CNKI, WANFANG Data, etc., for the fairness issues in medical AI through February 2023. The search was conducted using various keywords such as "artificial intelligence," "machine learning," "medical," "algorithm," "fairness," "decision-making," and "bias." The collected data were charted, synthesized, and subjected to descriptive and thematic analysis. RESULTS: After reviewing 468 English papers and 356 Chinese papers, 53 and 42 were included in the final analysis. Our results show the three different disciplines all show significant differences in the research on the core issues. Data is the foundation that affects medical AI fairness in addition to algorithmic bias and human bias. Legal, ethical, and technological measures all promote the implementation of medical AI fairness. CONCLUSIONS: Our review indicates a consensus regarding the importance of data fairness as the foundation for achieving fairness in medical AI across multidisciplinary perspectives. However, there are substantial discrepancies in core aspects such as the concept, influencing factors, and implementation measures of fairness in medical AI. Consequently, future research should facilitate interdisciplinary discussions to bridge the cognitive gaps between different fields and enhance the practical implementation of fairness in medical AI.

Frizzled-9 triggers actin polymerization and activates mechano-transducer YAP to rescue simulated microgravity-induced osteoblast dysfunction.

Long-term spaceflight can result in bone loss and osteoblast dysfunction. Frizzled-9 (Fzd9) is a Wnt receptor of the frizzled family that is vital for osteoblast differentiation and bone formation. In the present study, we elucidated whether Fzd9 plays a role in osteoblast dysfunction induced by simulated microgravity (SMG). After 1-7 days of SMG, osteogenic markers such as alkaline phosphatase (ALP), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2) were decreased, accompanied by a decrease in Fzd9 expression. Furthermore, Fzd9 expression decreased in the rat femur after 3 weeks of hindlimb unloading. In contrast, Fzd9 overexpression counteracted the decrease in ALP, OPN, and RUNX2 induced by SMG in osteoblasts. Moreover, SMG regulated phosphorylated glycogen synthase kinase-3ß (pGSK3ß) and ß-catenin expression or sublocalization. However, Fzd9 overexpression did not affect pGSK3ß and ß-catenin expression or sublocalization induced by SMG. In addition, Fzd9 overexpression regulated protein kinase B also known as Akt and extracellular signal-regulated kinase (ERK) phosphorylation and induced F-actin polymerization to form the actin cap, press the nuclei, and increase nuclear pore size, thereby promoting the nuclear translocation of Yes-associated protein (YAP). Our study findings provide mechanistic insights into the role of Fzd9 in triggering actin polymerization and activating YAP to rescue SMG-induced osteoblast dysfunction and suggest that Fzd9 is a potential target to restore osteoblast function in individuals with bone diseases and after spaceflight.

Lung specific homing of diphenyleneiodonium chloride improves pulmonary fibrosis by inhibiting macrophage M2 metabolic program.

INTRODUCTION: Pulmonary fibrosis (PF) is a fatal disease with a variable and unpredictable course. Effective clinical treatment for PF remains a challenge due to low drug accumulation in lungs and imbalanced polarization of pro/anti-fibrotic macrophages. OBJECTIVES: To identify the alteration of immunometabolism in the pulmonary macrophages and investigate the feasibility of specific inhibition of M2 activation of macrophages as an effective anti-PF strategy in vivo. METHODS: The high-content screening system was used to select lung-specific homing compounds that can modulate macrophage polarization. Imaging mass spectrometry (IMS) conjugated with chemical proteomics approach was conducted to explore the cells and proteins targeted by diphenyleneiodonium chloride (DPI). A bleomycin-induced fibrotic mouse model was established to examine the in vivo effect of DPI. RESULTS: Pulmonary macrophages of PF at late stage exhibited predominantly the M2 phenotype with decreased glycolysis metabolism. DPI was demonstrated to inhibit profibrotic activation of macrophages in the preliminary screening. Notably, IMS conjugated with chemical proteomics approach revealed DPI specifically targeted pulmonary macrophages, leading to the efficient protection from bleomycin-induced pulmonary fibrosis in mice. Mechanistically, DPI upregulated glycolysis and suppressed M2 programming in fibrosis mice, thus resulting in pro-fibrotic cytokine inhibition, hydroxyproline biosynthesis, and collagen deposition, with a concomitant increase in alveolar airspaces. CONCLUSIONS: DPI mediated glycolysis in lung and accordingly suppressed M2 programming, resulting in improved lung fibrosis.

Density-of-States Matching-Induced Ultrahigh Current Density and High-Humidity Resistance in a Simply Structured Triboelectric Nanogenerator.

Triboelectric nanogenerators (TENGs) can covert mechanical energy into electricity in a clean and sustainable manner. However, traditional TENGs are mainly limited by the low output current, and thus their practical applications are still limited. Herein, a new type of TENG is developed by using conductive materials as the triboelectric layers and electrodes simultaneously. Because of the matched density of states between the two triboelectric layers, this simply structured device reaches an open-circuit voltage of 1400 V and an ultrahigh current density of 1333 mA m-2 when poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) film and copper (Cu) or aluminum (Al) foil are used as the triboelectric pair. The current density increases by nearly three orders of magnitude compared with traditional TENGs. More importantly, this device can work stably in high-humidity environments, which is always a big challenge for traditional TENGs. Surprisingly, this TENG can even perform well in the presence of water droplets. This work provides a new and effective strategy for constructing high-performance TENGs, which can be used in many practical applications in the near future.

High-Performance Organic Electrochemical Transistor Based on Photo-annealed Plasmonic Gold Nanoparticle-Doped PEDOT:PSS.

Organic electrochemical transistors (OECTs), particularly the ones based on PEDOT:PSS, are excellent candidates for chemical and biological sensing because of their unique advantages. Improving the sensitivity and stability of OECTs is crucially important for practical applications. Herein, the transconductance of OECT is improved by 8-fold to 14.9 mS by doping the PEDOT:PSS channel with plasmonic gold nanoparticles (AuNPs) using a solution-based process followed by photo annealing. In addition, the OECT also possesses high flexibility and cyclic stability. It is revealed that the doping of AuNPs increases the conductivity of PEDOT:PSS and the photo annealing improves the crystallinity of the PEDOT:PSS channel and the interaction between AuNPs and PEDOT:PSS. These changes lead to the increase in transconductance and cyclic stability. The prepared OECTs are also demonstrated to be effective in sensitive detection of glucose within a wide concentration range of 10 nM-1 mM. Our OECTs based on photo-annealed plasmonic AuNP-doped PEDOT:PSS may find great applications in chemical and biological sensing, and this strategy may be extended to prepare many other high-performance OECT-based devices.

A Novel Design Concept of Cemented Paste Backfill (CPB) Materials: Biobjective Optimization Approach by Applying an Evolved Random Forest Model.

For cemented paste backfill (CPB), uniaxial compressive strength (UCS) is the key to ensuring the safety of stope construction, and its cost is an important part of the mining cost. However, there are a lack of design methods based on UCS and cost optimization. To address such issues, this study proposes a biobjective optimization approach by applying a novel evolved random forest (RF) model. First, the evolved RF model, based on the beetle search algorithm (BAS), was constructed to predict the UCS of CPB. The consistency between the predicted value and the actual value is high, which proves that the hybrid machine learning model has a good effect on the prediction of the UCS of CPB. Then, considering the linear relationship between the costs and the components of CPB, a mathematical model of the cost is constructed. Finally, based on the weighted sum method, the biobjective optimization process of the UCS and cost of CPB is conducted; the Pareto front optimal solutions of UCS and the cost of CPB can be obtained by the sort of solution set. When the UCS or the cost of CPB is constant, the Pareto front optimal solutions can always have a lower cost or a higher UCS compared with the actual dataset, which proves that the biobjective optimization approach has a good effect.

Mixture Optimization of Cementitious Materials Using Machine Learning and Metaheuristic Algorithms: State of the Art and Future Prospects.

The hybrid optimization of modern cementitious materials requires concrete to meet many competing objectives (e.g., mechanical properties, cost, workability, environmental requirements, and durability). This paper reviews the current literature on optimizing mixing ratios using machine learning and metaheuristic optimization algorithms based on past studies on varying methods. In this review, we first discuss the conventional methods for mixing optimization of cementitious materials. Then, the problem expression of hybrid optimization is discussed, including decision variables, constraints, machine learning algorithms for modeling objectives, and metaheuristic optimization algorithms for searching the best mixture ratio. Finally, we explore the development prospects of this field, including, expanding the database by combining field data, considering more influencing variables, and considering more competitive targets in the production of functional cemented materials. In addition, to overcome the limitation of the swarm intelligence-based multi-objective optimization (MOO) algorithm in hybrid optimization, this paper proposes a new MOO algorithm based on individual intelligence (multi-objective beetle antenna search algorithm). The development of computationally efficient robust MOO models will continue to make progress in the field of hybrid optimization. This review is adapted for engineers and researchers who want to optimize the mixture proportions of cementitious materials using machine learning and metaheuristic algorithms.

Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP.

Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1-6 dyn/cm2) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10 min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of Yes-associated protein (YAP). FSS activates p38, which plays a dual function in YAP regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP phosphorylation. AMOT competitively binds to F-actin and YAP to participate in FSS-mediated YAP nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-AMOT-YAP in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.

Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases.

As the first line of defence in the lung, alveolar macrophage contributes to maintaining lung immune homoeostasis. Characterized by the heterogeneity and plasticity, macrophages polarize into two pro-inflammatory and anti-inflammatory phenotypes regarding the biological and pathological environment. In the past decade, numerous studies have revolutionized the relationship between cellular metabolism and macrophage functions. Mitochondria dysfunctions, which results in altered cellular metabolic profile, were observed in the alveolar macrophages during chronic lung diseases. In addition, alveolar macrophages adapt metabolic reprogramming to produce an immune response against the pathogens. Here, we outline the role of mitochondria in the development of macrophage phenotypes and functions and highlight the mitochondrial dysfunction in the setting of chronic lung diseases. Lastly, we emphasize the therapeutic relevance of targeting metabolic pathways in alveolar macrophages, which may shed light on developing novel strategies against chronic lung diseases.

Groundwater quality assessment and hydrogeochemical processes in typical watersheds in Zhangjiakou region, northern China.

It is of significance to elucidate the groundwater quality and hydrogeochemical processes for sustainable utilization of groundwater resources in water shortage regions. A total of 256 groundwater samples were collected in typical watersheds in Zhangjiakou, northern China. The hydrochemical parameters, conventional ions, and trace elements were measured, and δD and δ18O data were collected to delineate the groundwater quality and hydrogeochemical processes. The results showed that 32.91% of the groundwater could be directly used for drinking water sources in the Bashang Plateau, north of the study area. The F- and NO3--N were the main parameters above the standard threshold for drinking water. In contrast, the groundwater quality in the Baxia River Basins, south of the study area, was of a better scenario. Nonetheless, high concentrations of F-, total hardness, and SO42- were still observed. Most samples in the Bashang Plateau had relatively higher salinity than the Baxia River Basins. Both surface water and groundwater in the study area originated from local meteoric water with considerable hydraulic connections. The high-fluoride groundwater was primarily formed by dissolution of fluoride-rich minerals under conditions of high pH and Na+, low Ca2+, and rich in HCO3-. The dissolution of carbonate and silicate minerals accompanied by strong cation exchange and weak evaporation was the dominant water-rock interaction affecting the hydrochemical composition of groundwater, and anthropogenic NO3- input had an extra influence on hydrochemical process. This study provides a scientific guideline for the protection and allocation of local groundwater resources.

MAdCAM-1 mediates retinal neuron degeneration in experimental colitis through recruiting gut-homing CD4+ T cells.

Extra-intestinal manifestations (EIMs) of the eyes are found in IBD patients, but the underlying pathogenesis remains unknown. To investigate the pathogenesis of IBD-associated retinal dysfunction, chronic colitis was induced in mice by oral administration of dextran sodium sulfate (DSS). Electroretinography (ERG) was performed to evaluate retinal function. Retinal neuron degeneration was analyzed by immunohistochemistry. Colitic mice displayed aberrant amplitudes of ERG a-, b-wave and oscillatory potentials (OP). Importantly, we observed severe degeneration of bipolar and ganglion cells. In contrast, outer retinal neurons (mainly photoreceptor cells) are mildly affected by colitis. Moreover, retinal inflammatory responses were significantly upregulated during colitis, including microglia activation, lymphocyte infiltration and cytokine/chemokine production. Notably, mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in retinal microvessels, especially the superficial and deep plexuses, and recruited gut-homing CD4+ T cells to be co-localized with bipolar and ganglion cells during colitis. Expectedly, in vivo depletion of CD4+ T cells or blockade of MAdCAM-1 greatly alleviated colitis-induced retinal inflammatory responses and neuron degeneration. Therefore, our data provide novel insight into the pathogenesis of IBD-associated retinal dysfunction, and targeted immune therapy directly against MAdCAM-1 might provide a novel approach in the management of eye EIM of IBD.

Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been well-documented as a chronic gastrointestinal autoimmune disease, but its etiology remains to be elusive. Ascl2 (achaete-scute complex homologue 2), identified as a homologue of the Drosophila achaete-scute gene, has been shown to play an essential for the pathogenesis of autoimmune diseases and cancers. However, whether it is associated with the pathogenesis of IBD remains unclear. Here, we demonstrated that Ascl2 was greatly down-regulated in human IBD and experimental colitis. Interestingly, CD4+ T cell expression of Ascl2 was regulated by intestinal microbiota. Moreover, we revealed that Ascl2 inhibited the differentiation of Th17 cells and restrained their pathogenicity through facilitating IL-10 production. We further showed that Blimp-1 might be involved in the Ascl2-inducing IL-10 expression in CD4+ T cells under Th17 differentiating condition. Notably, lentivirus-mediated overexpression of Ascl2 remarkably alleviated the severity of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice, with decreased level of colonic IL-17A. Our findings demonstrated an unappreciated mechanism whereby Ascl2 negatively modulates pathogenic Th17 cell differentiation via promoting IL-10 production, and alleviates intestinal inflammation. Thus, Ascl2 may serve as a novel therapeutic target of IBD.

Finite-element vibration analysis of tapping-mode atomic force microscopy in liquid.

Investigation of morphology and mechanical properties of biological specimens using atomic force microscopy (AFM) often requires its operation in liquid environment. Due to the hydrodynamic force, the vibration of AFM cantilevers in liquid shows dramatically different dynamic characteristics from that in air. A good understanding of the dynamics of AFM cantilevers vibrating in liquid is needed for the interpretation of scanning images, selection of AFM operating conditions, and evaluation of sample's mechanical properties. In this study, a finite element (FE) model is used for frequency and transient response analysis of AFM cantilevers in tapping mode (TM) operated in air or liquid. Hydrodynamic force exerted by the fluid on AFM cantilevers is approximated by additional mass and hydrodynamic damping. The additional mass and hydrodynamic damping matrices corresponding to beam elements are derived. With this model, numerical simulations are performed for an AFM cantilever to obtain the frequency and transient responses of the cantilever in air and liquid. The comparison between our simulated results and the experimentally obtained ones shows good agreement. Based on the simulations, different characteristics of cantilever dynamics in air and liquid are discussed.