Regulation of metabolic microenvironment with a nanocomposite hydrogel for improved bone fracture healing.

Bone nonunion poses an urgent clinical challenge that needs to be addressed. Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing. Macrophages and bone marrow-derived mesenchymal stromal cells (BMSCs) are important targets for therapeutic interventions in bone fractures. Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response. During osteogenic differentiation, BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate. Copper ion (Cu2+) is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis. In this study, we develop a 4-octyl itaconate (4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu2+ to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process. The findings reveal that burst release of 4-OI reduces the inflammatory response, promotes M2 macrophage polarization, and alleviates oxidative stress, while sustained release of Cu2+ stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis. Consequently, the 4-OI@Cu@Gel system achieves rapid fracture healing in mice. Thus, this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs.

In Vivo Evaluation of Corneal Biomechanics Following Cross-Linking Surgeries Using Optical Coherence Elastography in a Rabbit Model of Keratoconus.

Purpose: Validation of the feasibility of novel acoustic radiation force optical coherence elastography (ARF-OCE) for the evaluation of biomechanical enhancement of the in vivo model of keratoconus by clinical cross-linking (CXL) surgery. Methods: Twelve in vivo rabbit corneas were randomly divided into two groups. Both groups were treated with collagenase type II, and a keratoconus model was obtained. Then, the two groups were treated with CXL procedures with different irradiation energy of 15 J and 30 J (CXL-15 J and CXL-30 J, respectively). An ARF-OCE probe with an ultrasmall ultrasound transducer was used to detect the biomechanical properties of cornea. An antisymmetric Lamb wave model was combined with the frequency dispersion relationship to achieve depth-resolved elastography. Results: Compared with the phase velocity of the Lamb wave in healthy corneas (approximately 3.96 ± 0.27 m/s), the phase velocity of the Lamb wave was lower in the keratoconus region (P < 0.05), with an average value of 3.12 ± 0.12 m/s. Moreover, the corneal stiffness increased after CXL treatment (P < 0.05), and the average phase velocity of the Lamb wave was 4.3 ± 0.19 m/s and 4.54 ± 0.13 m/s after CXL-15 J and CXL-30 J treatment. Conclusions: The Young's moduli of the keratoconus regions were significantly lower than the healthy corneas. Moreover, the Young's modulus of the keratoconus regions was significantly higher after CXL-30 J treatment than after CXL-15 J treatment. We demonstrated that the ARF-OCE technique has great potential in screening keratoconus and guiding clinical CXL treatment. Translational Relevance: This work accelerates the clinical translation of OCE systems using ultrasmall ultrasound transducers and is used to guide CXL procedures.

Decoding the green supply chain: Education as the key to economic growth and sustainability.

The value of environmental safeguarding is rising in both private and public spheres. What is meant by the term "green supply chain management" (GSCM)? It is minimizing the negative effects of a company's operations on the natural world. Particularly in the research and academic disciplines of the expanding economy of the China region, the concept of the intersection of green supply chain management and sustainable development is dissected at a foundational level. However, there has been little attention paid to how GSCM, GHC, environmental performance, and economic performance all relate to one another. This study fills that void in the literature by giving hard data to encourage businesses in the China area to adopt GHC (green human capital) and SCM (sustainable supply chain management) in order to significantly improve their environmental and economic outcomes. To better understand the interplay between these ideas, we constructed a conceptual framework. The information was gathered using a survey consisting of questionnaires. Manufacturing companies from ten (10) different areas in China provided the 470 responses. The information was analyzed using structural equation modeling (SEM). Research shows that green human capital and green supply chain management have a beneficial influence on economic performance but no discernible effect on environmental outcomes. The results also demonstrate that green supply chain management is an effective act as a mediator between environmental performance and economic performance, with a beneficial effect on both. An initial conclusion may be made that bettering the green human capital stock was more important for China's green economy's growth than bettering the human capital structure. Research like this helps fill out the picture of the green economy and informs policy decisions at the national level.

Two-dimensional elastic distribution imaging of the sclera using acoustic radiation force optical coherence elastography.

The scleral elasticity is closely related with many ocular diseases, but the relevant research is still insufficient. Here, we utilized optical coherence elastography to carefully study biomechanical properties of the sclera at different positions and under different intraocular pressures. Meanwhile, elastic wave velocity and Young's modulus of each position were obtained using a phase velocity algorithm. Accordingly, the two-dimensional elasticity distribution image was achieved by mapping the Young's modulus values to the corresponding structure based on the relationship between the position and its Young's modulus. Therefore, elastic information in regions-of-interest can be read and compared directly from the scleral structure, indicating that our method may be a very useful tool to evaluate the elasticity of sclera and provide intuitive and reliable proof for diagnosis and research.

Variable stiffness soft robotic gripper: design, development, and prospects.

The advent of variable stiffness soft robotic grippers furnishes a conduit for exploration and manipulation within uncharted, non-structured environments. The paper provides a comprehensive review of the necessary technologies for the configuration design of soft robotic grippers with variable stiffness, serving as a reference for innovative gripper design. The design of variable stiffness soft robotic grippers typically encompasses the design of soft robotic grippers and variable stiffness modules. To adapt to unfamiliar environments and grasp unknown objects, a categorization and discussion have been undertaken based on the contact and motion manifestations between the gripper and the things across various dimensions: points contact, lines contact, surfaces contact, and full-bodies contact, elucidating the advantages and characteristics of each gripping type. Furthermore, when designing soft robotic grippers, we must consider the effectiveness of object grasping methods but also the applicability of the actuation in the target environment. The actuation is the propelling force behind the gripping motion, holding utmost significance in shaping the structure of the gripper. Given the challenge of matching the actuation of robotic grippers with the target scenario, we reviewed the actuation of soft robotic grippers. We analyzed the strengths and limitations of various soft actuation, providing insights into the actuation design for soft robotic grippers. As a crucial technique for variable stiffness soft robotic grippers, variable stiffness technology can effectively address issues such as poor load-bearing capacity and instability caused by the softness of materials. Through a retrospective analysis of variable stiffness theory, we comprehensively introduce the development of variable stiffness theory in soft robotic grippers and showcase the application of variable stiffness grasping technology through specific case studies. Finally, we discuss the future prospects of variable stiffness grasping robots from several perspectives of applications and technologies.

Novel acoustic radiation force optical coherence elastography based on ultrasmall ultrasound transducer for biomechanics evaluation of in vivo cornea.

We developed a novel acoustic radiation force optical coherence elastography (ARF-OCE) based on an ultrasmall ultrasound transducer for quantitative biomechanics evaluations of in vivo cornea. A custom single-sided meta-ultrasonic transducer with an outer diameter of 1.8 mm, focal spot diameter of 1.6 mm, central frequency of 930 kHz, and focal length of 0.8 mm was applied to excite the sample. The sample arm of the ARF-OCE system employed a three-dimensional printed holder that allowed for ultrasound excitation and ARF-OCE detection. The phase-resolved algorithm was combined with a Lamb wave model to depth-resolved evaluate corneal biomechanics after keratoconus and cross-linking treatments (CXL). The results showed that, compare to the healthy cornea, the Lamb wave velocity was significantly reduced in the keratoconus, increased in the cornea after CXL, and increased with cross-linked irradiation energy in the cornea. These results indicated the good clinical translation potential of the proposed novel ARF-OCE.

Dynamic evolution characteristics and driving factors of carbon emissions in prefecture-level cities in the Yellow River Basin of China.

This paper focuses on the spatiotemporal evolution characteristics, as well as the driving factors, of carbon emissions in the prefecture-level cities in the Yellow River Basin (YB). The paper's findings will aid in promoting ecological conservation and high-quality development in the region. The initiatives undertaken in the YB are a significant national strategy towards achieving carbon peaking and carbon neutrality. To fully investigate the spatiotemporal evolution process, as well as the typical characteristics of their carbon emissions, conventional, and spatial Markov transition probability matrices were developed utilizing YB's panel data for 55 prefecture-level cities from 2003 to 2019. The generalized Divisia index decomposition method (GDIM) cleverly uses this data to conduct a complete analysis of the dynamics and driving processes influencing the change in carbon emissions in these cities. However, the evolution of carbon emissions in prefecture-level cities has reached a point of stability that maintains the original state, making it challenging to make meaningful short-term progress. The data indicates that prefecture-level cities in the YB are emitting more carbon dioxide on average. Neighborhood types in these cities significantly influence the transformation of carbon emissions. Low-emission areas can encourage a reduction in carbon emissions, whereas high-emission areas can encourage an increase. The spatial organisation of carbon emissions exhibits a "high-high convergence, low-low convergence, high-pulling low, low-inhibiting high" club convergence phenomenon. Carbon emissions rise with per capita carbon emissions, energy consumed, technology, and output scale, whereas it falls with carbon technology intensity and output carbon intensity. Hence, instead of enhancing the role of increase-oriented variables, prefecture-level cities in the YB should actively engage these reduction-oriented forces. The YB's key pathways for lowering carbon emissions include boosting research and development, promoting and applying carbon emission reduction technologies, lowering output carbon intensity and energy intensity, and improving energy use effectiveness.

Acoustic radiation force optical coherence elastography: A preliminary study on biomechanical properties of trabecular meshwork.

Evaluating biomechanical properties of trabecular meshwork (TM) is of great significance for understanding the mechanism of aqueous humor circulation and its relationship to some eye diseases such as glaucoma; however, there is almost no relevant study due to the lack of clinical measurement tool. In this paper, an acoustic radiation force optical coherence elastography (ARF-OCE) system is developed with the advantages of noninvasive detection, high resolution, high sensitivity, and high-speed imaging, by which elastic modulus of the porcine and human TMs is accurately quantified. As the first OCE imaging of TM, our study demonstrates that ARF-OCE may be an effective approach to advance the research of diseases related to aqueous humor circulation.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes.

Postoperative cognitive dysfunction (POCD) is a common surgical complication. Diabetes mellitus (DM) increases risk of developing POCD after surgery. DM patients with POCD seriously threaten the quality of patients' life, however, the intrinsic mechanism is unclear, and the effective treatment is deficiency. Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD. In this study, we constructed a mouse model of DM by intraperitoneal injection of streptozotocin, and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion. We found that mouse models of DM-POCD exhibited the most serious cognitive impairment, as well as the most hippocampal neural stem cells (H-NSCs) loss and neurogenesis decline. Subsequently, we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) might promote neurogenesis and restore cognitive function in patients with DM-POCD. iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery, and then once every 3 days for 1 month thereafter. Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs, and reversed cognitive impairment in mouse models of DM-POCD. Furthermore, miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs. We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis. As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C, while miR-486-5p can inhibit FoxO1 in NSCs. We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4, CDKN2C, and FoxO1 expression in H-NSCs. Collectively, these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD, the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Annelid-inspired high-elongation origami robot using partial material removal.

Existing soft robots face challenges given the need for an improved flexible robot elongation rate, bending angle and movement flexibility in space target acquisition, disaster search and rescue, unknown environment detection and other fields. Yoshimura tubular origami shows good applied performance with regard to the axial elongation ratio. However, due to the characteristics of nonrigid folding and a negative Poisson's ratio, the axial elongation length and bending angle of the Yoshimura tubular origami mechanism are limited. Annelids show highly flexible body movement. By analyzing the main factors limiting the axial elongation rate of the Yoshimura tubular origami mechanism and imitating the morphological characteristics and motion mechanism of annelid somite joints, we proposed a method to achieve high flexibility and large angle bending of a tubular origami mechanism based on local material removal and macroscopic elimination of the negative Poisson's ratio. Combined with a Ni-Ti memory alloy wire segmented driving scheme based on force constraints and geometric constraints a continuous origami robot is designed. The optimal cutting amount of the origami mechanism is determined by experiments, and the maximum elongation ratio and bending angle of the origami mechanism reach 2.5 and 3 times those before material removal, respectively. The paper folding module unit was solved in a kinematic analysis workspace. Finally, a prototype was used to verify the performance and demonstrate the application potential of the robot in an unstructured rescue scene.

A novel design of a passive variable stiffness soft robotic gripper.

Inspired by the twisting and hanging phenomenon of vines, this paper proposes and designs a passive variable stiffness soft robotic gripper to grasp an object in a simple and robust manner using the principle of jamming. This method has the characteristics of high reliability and good stability, which can achieve soft grasping and rigid load-bearing of the object. Firstly, according to two key issues, the design model of the gripper is proposed, the principle of the proposed gripper is analyzed, and the relationship between the stiffness of the gripper and the stiffness of the object is revealed. Secondly, the model of the robotic gripper is created using a conventional motor drive method, and the grasping process and deformation causes of the gripper are analyzed by using the principle of instability effect and large deformation principle. Finally, the experimental prototype is developed and the feasibility of the design principle and the grasping deformation process of the gripper are verified by gripping experiments.

Quantitative Assessment of Biomechanical Properties of the Human Keratoconus Cornea Using Acoustic Radiation Force Optical Coherence Elastography.

Purpose: Quantification of biomechanical properties of keratoconus (KC) corneas has great significance for early diagnosis and treatment of KC, but the corresponding clinical measurement remains challenging. Here, we developed an acoustic radiation force (ARF) optical coherence elastography technique and explored its potential for evaluating biomechanical properties of KC corneas. Methods: An ARF system was used to induce the tissue deformation, which was detected by an optical coherence tomography system, and thus the localized point-by-point Young's modulus measurements were achieved. Then, two healthy rabbit eyes were imaged to test the system, after which the human keratoconus cornea was evaluated by using the same method. Three regions were selected for biomechanics analysis: the conical region, the transitional region, and the peripheral region. Results: Young's moduli of transitional region ranged from 53.3 to 58.5 kPa. The corresponding values for the peripheral region were determined to be 58.6 kPa and 63.2 kPa, respectively. Young's moduli of the conical region were gradually increased by 18.3% from the center to the periphery, resulting in the minimum and maximum values of 44.9 kPa and 53.1 kPa, respectively. Furthermore, Young's moduli of the anterior and posterior of the center were determined to be 44.9 kPa and 50.7 kPa, respectively. Conclusions: Differences in biomechanical properties between the three regions and slight variations within the conical region were clearly distinguished. Biomechanical weakening of the keratoconus cornea was mainly localized in the conical region, especially in the vertex position. Translational Relevance: The system may provide a promising clinical tool for the noninvasive evaluation of local corneal biomechanics and thus may have potential applications in early keratoconus detection with further optimization.

Quantification of biomechanical properties of human corneal scar using acoustic radiation force optical coherence elastography.

Biomechanical properties of corneal scar are strongly correlated with many corneal diseases and some types of corneal surgery, however, there is no elasticity information available about corneal scar to date. Here, we proposed an acoustic radiation force optical coherence elastography system to evaluate corneal scar elasticity. Elasticity quantification was first conducted on ex vivo rabbit corneas, and the results validate the efficacy of our system. Then, experiments were performed on an ex vivo human scarred cornea, where the structural features, the elastic wave propagations, and the corresponding Young's modulus of both the scarred region and the normal region were achieved and based on this, 2D spatial distribution of Young's modulus of the scarred cornea was depicted. Up to our knowledge, we realized the first elasticity quantification of corneal scar, which may provide a potent tool to promote clinical research on the disorders and surgery of the cornea.

Quantitative Evaluation of In Vivo Corneal Biomechanical Properties after SMILE and FLEx Surgery by Acoustic Radiation Force Optical Coherence Elastography.

The purpose of this study is to quantitatively evaluate the differences in corneal biomechanics after SMILE and FLEx surgery using an acoustic radiation force optical coherence elastography system (ARF-OCE) and to analyze the effect of the corneal cap on the integrity of corneal biomechanical properties. A custom ring array ultrasound transducer is used to excite corneal tissue to produce Lamb waves. Depth-resolved elastic modulus images of the in vivo cornea after refractive surgery were obtained based on the phase velocity of the Lamb wave. After refractive surgery, the average elastic modulus of the corneal flap decreased (71.7 ± 24.6 kPa), while the elastic modulus of the corneal cap increased (219.5 ± 54.9 kPa). The average elastic modulus of residual stromal bed (RSB) was increased after surgery, and the value after FLEx (305.8 ± 48.5 kPa) was significantly higher than that of SMILE (221.3 ± 43.2 kPa). Compared with FLEx, SMILE preserved most of the anterior stroma with less change in corneal biomechanics, which indicated that SMILE has an advantage in preserving the integrity of the corneal biomechanical properties. Therefore, the biomechanical properties of the cornea obtained by the ARF-OCE system may be one of the essential indicators for evaluating the safety of refractive surgery.

In Vivo Evaluation of the Effects of SMILE with Different Amounts of Stromal Ablation on Corneal Biomechanics by Optical Coherence Elastography.

This work aims to depth-resolved quantitatively analyze the effect of different stromal ablation amounts on the corneal biomechanical properties during small incision lenticule extraction (SMILE) using optical coherence elastography (OCE). A 4.5-MHz ultrasonic transducer was used to excite elastic waves in the corneal tissue. The OCE system combined with the antisymmetric Lamb wave model was employed to achieve a high-resolution, high-sensitivity, and depth-resolved quantitative detection of the corneal Young's modulus. Eighteen rabbits were randomly divided into three groups; each group had six rabbits. The first and second groups underwent -3D and -6D SMILE surgeries, and the third group was the control group, respectively. Young's modulus of the corneal cap and residual stromal bed (RSB) were both increased after SMILE, which shared the stress under intraocular pressure (IOP). Furthermore, the Young's modulus of both the corneal cap and RSB after 3D SMILE group were significantly lower than that in the -6D group, which indicated that the increases in the post-operative corneal Young's modulus were positively correlated with the amount of stromal ablation. The OCE system for quantitative spatial characterization of corneal biomechanical properties can provide useful information on the extent of safe ablation for SMILE procedures.

A highly efficient Fe-Ni-S/NF hybrid electrode for promoting oxygen evolution performance.

In this study, a Fe-Ni-S/NF hybrid electrode with a hierarchical structure was fabricated via a simple hydrothermal and ion exchange method, and it exhibited remarkable OER performance in an alkaline solution at an ultralow overpotential (1000 mA cm-2@384 mV) and outstanding operational stability.

Effects of lumican expression on the apoptosis of scleral fibroblasts: In vivo and in vitro experiments.

Lumican serves an important role in the maintenance of sclera biomechanical properties. However, whether lumican expression is altered in myopia and the mechanisms of action involved are unknown. In the present study, the expression of lumican in cultured scleral fibroblasts and in the scleral tissue of a rat model of form-deprivation myopia was assessed. It was confirmed that diopter was decreased, whereas axial length was increased in modeled eyes relative to normal control eyes, indicating that the model of myopia was successfully established. These pathologic changes were accompanied by the upregulation of lumican and tissue inhibitor of metalloproteinases (TIMP)-2, as well as the downregulation of matrix metalloproteinase (MMP)-2 and MMP-14. The same trends in TIMP-2, MMP-2 and MMP-14 expression were observed when lumican was overexpressed in cultured scleral fibroblasts. Additionally, cell proliferation decreased whereas apoptosis increased compared with those of control cells. Inhibiting lumican expression had no effect on cell proliferation or apoptosis, but stimulated the expression of MMP-2 and MMP-14 while decreasing that of TIMP-2. The results suggested that lumican overexpression contributed to myopia by promoting apoptosis in scleral fibroblasts via the modulation of TIMP-2, MMP-2 and MMP-14 expression.

The effect of SiNPs on DNA methylation of genome in mouse spermatocytes.

Silica nanoparticles (SiNPs), which are the main inorganic components of atmospheric particulate matter, have been proved to have certain male reproductive toxicity in previous studies. Spermatogenesis involves complex epigenetic regulation, but it is still unclear if SiNPs exposure will interfere with the DNA methylation patterns in mouse spermatocytes. The present study was designed to investigate the effects of SiNPs on DNA methylation in the mouse spermatocyte GC-2spd(ts). GC-2 cells were treated with 0 and 20 µg/mL SiNPs for 24 h. MeDIP-seq assay was then performed to analyze the differentially methylated genes related to spermatogenesis. The results showed that SiNPs induced extensive methylation changes in the genome of GC-2 cells, and 24a total of 428 hyper-methylated genes and 398 hypo-methylated genes were identified. Gene Ontology and pathway analysis showed that differential DNA methylation induced by SiNPs was probably involved with abnormal transcription and translation, mitochondrial damage, and cell apoptosis. Results from qRT-PCR verification showed that the expression of spermatogenesis-related genes Akap1, Crem, Spz1, and Tex11 were dysregulated by SiNPs exposure, which was consistent with the MeDIP-seq assay. In general, this study suggested that SiNPs caused genome-wide DNA methylation changes in GC-2 cells, providing valuable reference for the future epigenetic studies in SiNPs-induced male reproductive toxicity.

Big Five Personality, Academic Entrepreneurial Motivation, and Academic Entrepreneurial Intention: A Research Method Based on Fuzzy Set Qualitative Comparative Analysis.

Scholars are the main force behind academic entrepreneurship. The method of how to stimulate scholars' academic entrepreneurial intention and how to further promote social and economic development are important questions for the academic community. Research on the "net effect" of the factors affecting academic entrepreneurial intention has achieved some theoretical results. However, the results that affect academic entrepreneurial intention are complex and not influenced by a single factor, but rather by the interaction between various factors. Therefore, this study used a fuzzy set qualitative comparative analysis research method to explore how various factors can affect scholars' academic entrepreneurial intention from two dimensions: the Big Five personality traits and academic entrepreneurial motivation. Our findings showed two configurations that affect high academic entrepreneurial intention of university scholars: the openness to experience-ribbon-dominant path, and the ribbon-dominant path. Additionally, two configurations were revealed for the formation of not-high academic entrepreneurial intention: extraversion-conscientiousness-inhibition and extraversion-agreeableness-gold-hindrance paths. Moreover, this study revealed that a causal asymmetry exists between the high and the not-high academic entrepreneurial intention configurations. This study broadens the application of the fuzzy set qualitative comparative analysis method in the research of academic entrepreneurial intention and provides theoretical and practical insights for researchers and practitioners on how to effectively stimulate scholars' academic entrepreneurial intention.

The alterations of miRNA and mRNA expression profile and their integration analysis induced by silica nanoparticles in spermatocyte cells.

Air pollution and the application of Silica nanoparticles (SiNPs) have increased the risk of human exposure to SiNPs. SiNPs are known to induce cytotoxicity in spermatocyte cells (GC-2spd cells) of mice and male reproductive system damage. However, the expression profiles of miRNA and mRNA and the molecular mechanism of miRNA-mRNA integration in reproductive toxicity induced by SiNPs in GC-2spd cells are still unclear. Therefore, GC-2spd cells were divided into 0 µg/mL and 5 µg/mL SiNPs groups, and the cells were collected and analyzed after passaging for 30 generations using miRNA microarray and Illumina high-throughput sequencing (Illumina HiSeq) for the integrated analysis of miRNA and mRNA expression. Both miRNA Microarray and Illumina Hiseq identified 15 significant differentially expressed miRNAs and 1648 significant differentially expressed mRNAs. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and miRNA-gene-pathway-network analysis revealed 15 significant differentially expressed miRNAs that could regulate the DNA replication and the fatty acid metabolism, respectively. Furthermore, the mRNA-mRNA regulatory network analysis revealed that Pkfl (phosphofructokinase, liver, B-type) and DHCR24 (24-dehydrocholesterol reductase) were highly expressed, but also affected DNA replication and fatty acid metabolism in SiNPs-treated GC-2spd cells. Additionally, miRNA-mRNA integration analysis revealed that miRNA-138-1-3p might have a regulatory relationship with fatty acid metabolism and DNA replication. It is confirmed that SiNPs could decrease the expression of 10 miRNAs and increase the expression of 5 miRNAs. These findings suggest that the cytotoxicity of GC-2spd cells induced by SiNPs depends on the deregulation of multiple miRNAs, which regulate the DNA replication and fatty acid metabolism. Our results are the first to establish an integrated analysis of miRNA-mRNA interactions and mRNA-mRNA and defines multiple pathways involved in SiNPs-treated GC-2spd cells.