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In the evolving landscape of higher education, challenges such as the COVID-19 pandemic have underscored the necessity for innovative teaching methodologies. These challenges have catalyzed the integration of technology into education, particularly in blended learning environments, to bolster self-regulated learning (SRL) and higher-order thinking skills (HOTS). However, increased autonomy in blended learning can lead to learning disruptions if issues are not promptly addressed. In this context, OpenAI's ChatGPT, known for its extensive knowledge base and immediate feedback capability, emerges as a significant educational resource. Nonetheless, there are concerns that students might become excessively dependent on such tools, potentially hindering their development of HOTS. To address these concerns, this study introduces the Guidance-based ChatGPT-assisted Learning Aid (GCLA). This approach modifies the use of ChatGPT in educational settings by encouraging students to attempt problem-solving independently before seeking ChatGPT assistance. When engaged, the GCLA provides guidance through hints rather than direct answers, fostering an environment conducive to the development of SRL and HOTS. A randomized controlled trial (RCT) was employed to examine the impact of the GCLA compared to traditional ChatGPT use in a foundational chemistry course within a blended learning setting. This study involved 61 undergraduate students from a university in Taiwan. The findings reveal that the GCLA enhances SRL, HOTS, and knowledge construction compared to traditional ChatGPT use. These results directly align with the research objective to improve learning outcomes through providing guidance rather than answers by ChatGPT. In conclusion, the introduction of the GCLA has not only facilitated more effective learning experiences in blended learning environments but also ensured that students engage more actively in their educational journey. The implications of this study highlight the potential of ChatGPT-based tools in enhancing the quality of higher education, particularly in fostering essential skills such as self-regulation and HOTS. Furthermore, this research offers insights regarding the more effective use of ChatGPT in education.

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

Wave erosion of slopes can easily trigger landslides into marine environments and pose severe threats to both the ecological environment and human activities. Therefore, near-shore slope monitoring becomes crucial for preventing and alerting people to these potential disasters. To achieve a comprehensive understanding, it is imperative to conduct a detailed investigation into the dynamics of wave erosion processes acting on slopes. This research is conducted through flume tests, using a wave maker to create waves of various heights and frequencies to erode the slope models. During the tests, seismic signals, acoustic signals, and pore pressure generated by wave erosion and slope failure are recorded. Seismic and acoustic signals are analyzed, and time-frequency spectra are calculated using the Hilbert–Huang Transform to identify the erosion events and signal frequency ranges. Arias Intensity is used to assess seismic energy and explore the relationship between the amount of erosion and energy. The results show that wave height has a more decisive influence on erosion behavior and retreat than wave frequency. Rapid drawdown may potentially cause the slope to slide during cyclic swash and backwash wave action. As wave erosion changes from swash to impact, there is a significant increase in the spectral magnitude and Power Spectral Density (PSD) of both seismic and acoustic signals. An increase in pore pressure is observed due to the rise in the run-up height of waves. The amplitude of pore pressure will increase as the slope undergoes further erosion. Understanding the results of this study can aid in predicting erosion and in planning effective management strategies for slopes subject to wave action.

Multidrug resistance (MDR) remains the most difficult problem facing conventional chemotherapy for cancers. Astragalus membranaceus is a historically traditional Chinese medicine. One of its bioactive components, formononetin, exhibits antitumor effects on various cancers. However, the effects of formononetin on MDR cancers have not been evaluated. Therefore, we investigated the defense’s effects of formononetin on MDR. We used rhodamine 123 and doxorubicin efflux assays to analyze the inhibition kinetics of P-glycoprotein (P-gp) mediated-efflux. Cell viability was detected by sulforhodamine B assay, and the synergistic effects of formononetin combined with chemotherapeutic agents were further calculated using CompuSyn software. Molecular docking was performed with iGEMDOCK. We discovered that formononetin considerably induced oxidative stress and the disruption of mitochondrial membrane potential in MDR cancer cells. Furthermore, formononetin inhibits the P-gp efflux function by ATPase stimulation and the uncompetitive inhibition of P-gp-mediated effluxes of rhodamine 123 and doxorubicin. The molecular docking model indicates that formononetin may bind to P-gp by strong hydrogen bonds at Arginine (Arg) 489 and Glutamine (Gln) 912. Formononetin exhibits significant synergistic effects with vincristine and doxorubicin toward MDR cancer cells, and it synergistically suppressed tumor growth in vivo with paclitaxel. These results suggest that formononetin should be seen as a potential candidate for the adjuvant therapy of MDR cancers.

To achieve the optimal alginate-based oral formulation for delivery of hydrophobic drugs, on the basis of previous research, we further optimized the synthesis process parameters of alginate-g-oleylamine derivatives (Ugi-FOlT) and explored the effects of different degrees of substitution (DSs) on the molecular self-assembly properties of Ugi-FOlT, as well as the in vitro cytotoxicity and drug release behavior of Ugi-FOlT. The resultant Ugi-FOlT exhibited good amphiphilic properties with the critical micelle concentration (CMC) ranging from 0.043 mg/mL to 0.091 mg/mL, which decreased with the increase in the DS of Ugi-FOlT. Furthermore, Ugi-FOlT was able to self-assemble into spherical micellar aggregates in aqueous solution, whose sizes and zeta potentials with various DSs measured by dynamic light scattering (DLS) were in the range of 653 ± 25~710 ± 40 nm and −58.2 ± 1.92~−48.9 ± 2.86 mV, respectively. In addition, RAW 264.7 macrophages were used for MTT assay to evaluate the in vitro cytotoxicity of Ugi-FOlT in the range of 100~500 μg/mL, and the results indicated good cytocompatibility for Ugi-FOlT. Ugi-FOlT micellar aggregates with favorable stability also showed a certain sustained and pH-responsive release behavior for the hydrophobic drug ibuprofen (IBU). Meanwhile, it is feasible to control the drug release rate by regulating the DS of Ugi-FOlT. The influence of different DSs on the properties of Ugi-FOlT is helpful to fully understand the relationship between the micromolecular structure of Ugi-FOlT and its macroscopic properties.

The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFβ, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFβ-related signal pathway.

Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.

This study assessed the biocompatibility of two types of nanogold composites: fibronectin-gold (FN-Au) and collagen-gold (Col-Au). It consisted of three main parts: surface characterization, in vitro biocompatibility assessments, and animal models. To determine the structural and functional differences between the materials used in this study, atomic force microscopy, Fourier-transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to investigate their surface topography and functional groups. The F-actin staining, proliferation, migration, reactive oxygen species generation, platelet activation, and monocyte activation of mesenchymal stem cells (MSCs) cultured on the FN-Au and Col-Au nanocomposites were investigated to determine their biological and cellular behaviors. Additionally, animal biocompatibility experiments measured capsule formation and collagen deposition in female Sprague–Dawley rats. The results showed that MSCs responded better on the FN-Au and Col-AU nanocomposites than on the control (tissue culture polystyrene) or pure substances, attributed to their incorporation of an optimal Au concentration (12.2 ppm), which induced significant surface morphological changes, nano topography cues, and better biocompatibility. Moreover, neuronal, endothelial, bone, and adipose tissues demonstrated better differentiation ability on the FN-Au and Col-Au nanocomposites. Nanocomposites have a crucial role in tissue engineering and even vascular grafts. Finally, MSCs were demonstrated to effectively enhance the stability of the endothelial structure, indicating that they can be applied as promising alternatives to clinics in the future.

The tomato fruit is a complex organ and is composed of various structures from the inside out, such as columella, septum, and placenta. However, our understanding of the development and function of these internal structures remains limited. In this study, we identified a plant-specific YABBY protein, SlYABBY2a, in the tomato (Solanum lycopersicum). SlYABBY2a exhibits relatively high expression levels among the nine YABBY genes in tomatoes and shows specific expression in the septum of the fruit. Through the use of a gene-editing technique performed by CRISPR/Cas9, we noticed defects in septum development in the Slyabby2a mutant fruits, leading to the inward concavity of the fruit pericarp and delayed septum ripening. Notably, the expression levels of key genes involved in auxin (SlFZY4, SlFZY5, and SlFZY6) and ethylene (SlACS2) biosynthesis were significantly downregulated in the septum of the Slalkbh10b mutants. Furthermore, the promoter activity of SlYABBY2a was regulated by the ripening regulator, SlTAGL1, in vivo. In summary, these discoveries provide insights into the positive regulation of SlYABBY2a on septum development and ripening and furnish evidence of the coordinated regulation of the auxin and ethylene signaling pathways in the ripening process, which expands our comprehension of septum development in the internal structure of the fruit.

ALKBH proteins, the homologs of Escherichia coli AlkB dioxygenase, constitute a single-protein repair system that safeguards cellular DNA and RNA against the harmful effects of alkylating agents. ALKBH10B, the first discovered N6-methyladenosine (m6A) demethylase in Arabidopsis (Arabidopsis thaliana), has been shown to regulate plant growth, development, and stress responses. However, until now, the functional role of the plant ALKBH10B has solely been reported in arabidopsis, cotton, and poplar, leaving its functional implications in other plant species shrouded in mystery. In this study, we identified the AlkB homolog SlALKBH10B in tomato (Solanum lycopersicum) through phylogenetic and gene expression analyses. SlALKBH10B exhibited a wide range of expression patterns and was induced by exogenous abscisic acid (ABA) and abiotic stresses. By employing CRISPR/Cas9 gene editing techniques to knock out SlALKBH10B, we observed an increased sensitivity of mutants to ABA treatment and upregulation of gene expression related to ABA synthesis and response. Furthermore, the Slalkbh10b mutants displayed an enhanced tolerance to drought and salt stress, characterized by higher water retention, accumulation of photosynthetic products, proline accumulation, and lower levels of reactive oxygen species and cellular damage. Collectively, these findings provide insights into the negative impact of SlALKBH10B on drought and salt tolerance in tomato plant, expanding our understanding of the biological functionality of SlALKBH10B.

Bacterial infections have become a serious threat to global public health. Nanomaterials have shown promise in the development of bacterial biosensing and antibiotic-free antibacterial modalities, but single-component materials are often less functional and difficult to achieve dual bacterial detection and killing. Herein, we report a novel strategy based on the effective integration of multi-modal bacterial detection and elimination, by constructing the versatile gold-silver-Prussian blue nanojujubes (GSP NJs) via a facile template etching method. Such incorporation of multi-components involves the utilization of cores of gold nanobipyramids with strong surface-enhanced Raman scattering (SERS) activity, the shells of Prussian blue as both an efficient bio-silent SERS label and an active peroxidase-mimic, and functionalization of polyvinyl pyrrolidone and vancomycin, respectively endowing them with good colloidal dispersibility and specificity against S. aureus. The GSP NJs show operational convenience in the SERS detection and excellent peroxidase-like activity for the sensitive colorimetric detection. Meanwhile, they exhibit robust near-infrared photothermal/photodynamic effects, and the photo-promoted Ag+ ions release, ultimately achieving a high antibacterial efficiency over 99.9% in 5 min. The NJs can also effectively eliminate complex biofilms. The work provides new insights into the design of multifunctional core-shell nanostructures for the integrated bacterial detection and therapy.

Types of nanozymes can produce free radicals and/or reactive oxygen species (ROS) to serve as broad spectrum antibacterial materials. Developing nanozyme-based antibacterial materials with good biocompatibility exhibits promising application prospects. In this study, we doped Mo to ZIF-8 (both components have good biocompatibility) to prepare a new nanozyme, Mo@ZIF-8, which can produce hydroxyl radicals (•OH) triggered by a low dosage of hydrogen peroxide (H2O2), exhibiting effective antibacterial capability against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). This work provides a reference for the design of antibacterial nanozymes with good biocompatibility.

SnRK2.6 (SUCROSE NONFERMENTING 1-RELATED PROTEIN KINASE2.6) has been characterized as a molecular switch for the intracellular abscisic acid (ABA) signal-transduction pathway. Normally, SnRK2.6 is kept in an “off” state, forming a binary complex with protein phosphatase type 2Cs (PP2Cs). Upon stressful conditions, SnRK2.6 turns into an “on” state by its release from PP2Cs and then phosphorylation at Ser175. However, how the ”on” and “off” states for SnRK2.6 are fine-tuned, thereby controlling the initiation and braking processes of ABA signaling, is still largely unclear. SnRK2.6 activity was tightly regulated through protein post-translational modifications (PTM), such as persulfidation and phosphorylation. Taking advantage of molecular dynamics simulations, our results showed that Cys131/137 persulfidation on SnRK2.6 induces destabilized binding and weakened interactions between SnRK2.6 and HAB1 (HYPERSENSITIVE TO ABA1), an important PP2C family protein. This unfavorable effect on the association of the SnRK2.6–HAB1 complex suggests that persulfidation functions are a positive regulator of ABA signaling initiation. In addition, Ser267 phosphorylation in persulfidated SnRK2.6 renders a stable physical association between SnRK2.6 and HAB1, a key characterization for SnRK2.6 inhibition. Rather than Ser175, HAB1 cannot dephosphorylate Ser267 in SnRK2.6, which implies that the retained phosphorylation status of Ser267 could ensure that the activated SnRK2.6 reforms the binary complex to cease ABA signaling. Taken together, our findings expand current knowledge concerning the regulation of persulfidation and phosphorylation on the state transition of SnRK2.6 and provide insights into the fine-tuned mechanism of ABA signaling.

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-β1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

The currently reported methods for preparing cellulose acetate hydrogels use chemical reagents as cross-linking agents, and the prepared ones are non-porous structured cellulose acetate hydrogels. Nonporous cellulose acetate hydrogels limit the range of applications, such as limiting cell attachment and nutrient delivery in tissue engineering. This research creatively proposed a facile method to prepare cellulose acetate hydrogels with porous structures. Water was added to the cellulose acetate–acetone solution as an anti-solvent to induce the phase separation of the cellulose acetate–acetone solution to obtain a physical gel with a network structure, where the cellulose acetate molecules undergo re-arrangement during the replacement of acetone by water to obtain hydrogels. The SEM and BET test results showed that the hydrogels are relatively porous. The maximum pore size of the cellulose acetate hydrogel is 380 nm, and the specific surface area reaches 62 m2/g. The porosity of the hydrogel is significantly higher than that of the cellulose acetate hydrogel reported in the previous literature. The XRD results show that the nanofibrous morphology of cellulose acetate hydrogels is caused by the deacetylation reaction of cellulose acetate.

We have designed and synthesized a novel simple colorimetric fluorescent probe with aggregation-induced emission (AIE) properties. Probe 5-(4-(diphenylamine)phenyl) thiophen-2-formaldehyde W exhibited a turn-on fluorescent response to cyanide ion (CN−), which induces distinct visual color changes. Probe W exhibited a highly selective and sensitive ratiometric fluorescence response for the detection of CN− over a wide pH range (4–11) and in the presence of common interferents. The linear detection of CN− over the concentration range of 4.00–38.00 µM (R2 = 0.9916, RSD = 0.02) was monitored by UV-Vis absorption spectrometry (UV-Vis) with the limit of detection determined to be 0.48 µM. The linear detection of CN− over the concentration range of 8.00–38.00 µM was examined by fluorescence spectrophotometry (R2 = 0.99086, RSD = 0.031), and the detection limit was found to be 68.00 nM. The sensing mechanisms were confirmed by 1H NMR spectroscopic titrations, X-ray crystallographic analysis, and HRMS. Importantly, probe W was found to show rapid response, high selectivity, and sensitivity for cyanide anions in real water samples, over the range of 100.17∼100.86% in artificial lake water and 100.54∼101.64% in running water by UV-Vis absorption spectrometry, and over the range of 99.42∼100.71% in artificial lake water and 100.59∼101.17% in running water by fluorescence spectrophotometry. Importantly, this work provides a simple and effective approach which uses an economically cheap and uncomplicated synthetic route for the selective, sensitive, and quantitative detection of CN− ions in systems relevant to the environment and health.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

The major oxidized product of cholesterol, 7-Ketocholesterol (7KCh), causes cellular oxidative damage. In the present study, we investigated the physiological responses of cardiomyocytes to 7KCh. A 7KCh treatment inhibited the growth of cardiac cells and their mitochondrial oxygen consumption. It was accompanied by a compensatory increase in mitochondrial mass and adaptive metabolic remodeling. The application of [U-13C] glucose labeling revealed an increased production of malonyl-CoA but a decreased formation of hydroxymethylglutaryl-coenzyme A (HMG-CoA) in the 7KCh-treated cells. The flux of the tricarboxylic acid (TCA) cycle decreased, while that of anaplerotic reaction increased, suggesting a net conversion of pyruvate to malonyl-CoA. The accumulation of malonyl-CoA inhibited the carnitine palmitoyltransferase-1 (CPT-1) activity, probably accounting for the 7-KCh-induced suppression of β-oxidation. We further examined the physiological roles of malonyl-CoA accumulation. Treatment with the inhibitor of malonyl-CoA decarboxylase, which increased the intracellular malonyl-CoA level, mitigated the growth inhibitory effect of 7KCh, whereas the treatment with the inhibitor of acetyl-CoA carboxylase, which reduced malonyl-CoA content, aggravated such a growth inhibitory effect. Knockout of malonyl-CoA decarboxylase gene (Mlycd−/−) alleviated the growth inhibitory effect of 7KCh. It was accompanied by improvement of the mitochondrial functions. These findings suggest that the formation of malonyl-CoA may represent a compensatory cytoprotective mechanism to sustain the growth of 7KCh-treated cells.

Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that β-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.

MXene materials have the metallic conductivity of transition metal carbides. Among them, Ti3C2TX with an accordion structure has great application prospects in the field of wearable devices. However, flexible wearable electronic devices face the problem of single function in practical application. Therefore, it is particularly important to study a flexible sensor with multiple functions for electronic skin. In this work, the near-field electrohydrodynamic printing (NFEP) method was proposed to prepare the composite thin film with a micro/nanofiber structure on the flexible substrate using a solution of poly(vinylidene fluoride)/MXene nanosheet/reduced graphene oxide (PMR) nanocomposites as the printing solution. A dual-mode flexible sensor for electronic skin based on the PMR nanocomposite thin film was fabricated. The flexible sensor had the detection capability of the piezoresistive mode and the piezoelectric mode. In the piezoresistive mode, the sensitivity was 29.27 kPa−1 and the response/recovery time was 36/55 ms. In the piezoelectric mode, the sensitivity was 8.84 kPa−1 and the response time was 18.2 ms. Under the synergy of the dual modes, functions that cannot be achieved by a single mode sensor can be accomplished. In the process of detecting the pressure or deformation of the object, more information is obtained, which broadens the application range of the flexible sensor. The experimental results show that the dual-mode flexible sensor has great potential in human motion monitoring and wearable electronic device applications.

The efficient recycling of valuable resources from rolling oil sludge (ROS) to gain new uses remains a formidable challenge. In this study, we reported the recycling of solid Fe resources from ROS by a catalytic hydrogenation technique and its catalytic performance for CO oxidation. The solid Fe resources, after calcination in air (Fe2O3-H), exhibited comparable activity to those prepared by the calcinations of ferric nitrate (Fe2O3-C), suggesting that the solid resources have excellent recycling value when used as raw materials for CO oxidation catalyst preparation. Further studies to improve the catalytic performance by supporting the materials on high surface area 13X zeolite and by pretreating the materials with CO atmosphere, showed that the CO pretreatment greatly improved the CO oxidation activity and the best activity was achieved on the 20 wt.%Fe2O3-H/13X sample with complete CO conversion at 250 °C. CO pretreatment could produce more oxygen vacancies, facilitating O2 activation, and thus accelerate the CO oxidation reaction rate. The excellent reducibility and sufficient O2 adsorption amount were also favorable for its performance. The recycling of solid Fe resources from ROS is quite promising for CO oxidation applications.

Pulmonary arterial hypertension (PAH) is a fatal or life-threatening disorder characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance. Abnormal vascular remodeling, including the proliferation and phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs), represents the most critical pathological change during PAH development. Previous studies showed that miR-486 could reduce apoptosis in different cells; however, the role of miR-486 in PAH development or HPASMC proliferation and migration remains unclear. After 6 h of hypoxia treatment, miR-486-5p was significantly upregulated in HPASMCs. We found that miR-486-5p could upregulate the expression and secretion of ET-1. Furthermore, transfection with a miR-486-5p mimic could induce HPASMC proliferation and migration. We also found that miRNA-486-5p could downregulate the expression of SMAD2 and the phosphorylation of SMAD3. According to previous studies, the loss of SMAD3 may play an important role in miRNA-486-5p-induced HPASMC proliferation. Although the role of miRNA-486-5p in PAH in in vivo models still requires further investigation and confirmation, our findings show the potential roles and effects of miR-486-5p during PAH development.

Microglia, astrocytes, and oligodendrocyte progenitor cells (OPCs) may serve as targets for remyelination-enhancing therapy. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to ameliorate myelin loss and inhibit neuroinflammation in animal models of brain disorders; however, the underlying mechanisms through which LIPUS stimulates remyelination and glial activation are not well-understood. This study explored the impacts of LIPUS on remyelination and resident cells following lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 μL of 1% LPC into the rat hippocampus, and the treatment groups received daily LIPUS stimulation for 5 days. The therapeutic effects of LIPUS on LPC-induced demyelination were assessed through immunohistochemistry staining. The staining was performed to evaluate remyelination and Iba-1 staining as a microglia marker. Our data revealed that LIPUS significantly increased myelin basic protein (MBP) expression. Moreover, the IHC results showed that LIPUS significantly inhibited glial cell activation, enhanced mature oligodendrocyte density, and promoted brain-derived neurotrophic factor (BDNF) expression at the lesion site. In addition, a heterologous population of microglia with various morphologies can be found in the demyelination lesion after LIPUS treatment. These data show that LIPUS stimulation may serve as a potential treatment for accelerating remyelination through the attenuation of glial activation and the enhancement of mature oligodendrocyte density and BDNF production.

Interleukin-23 (IL-23) plays a pivotal role in rheumatoid arthritis (RA). IL-23 and microRNA-223 (miR-223) are both up-regulated and mediate osteoclastogenesis in mice with collagen-induced arthritis (CIA). The aim of this study was to examine the association between IL-23 and miR-223 in contributing to osteoclastogenesis and arthritis. Levels of IL-23p19 in joints of mice with CIA were determined. Lentiviral vectors expressing short hairpin RNA (shRNA) targeting IL-23p19 and lisofylline (LSF) were injected intraperitoneally into arthritic mice. Bone marrow-derived macrophages (BMMs) were treated with signal transducers and activators of transcription 4 (STAT4) specific shRNA and miR-223 sponge carried by lentiviral vectors in response to IL-23 stimulation. Treatment responses were determined by evaluating arthritis scores and histopathology in vivo, and detecting osteoclast differentiation and miR-223 levels in vitro. The binding of STAT4 to the promoter region of primary miR-223 (pri-miR-223) was determined in the Raw264.7 cell line. IL-23p19 expression was increased in the synovium of mice with CIA. Silencing IL-23p19 and inhibiting STAT4 activity ameliorates arthritis by reducing miR-223 expression. BMMs from mice in which STAT4 and miR-223 were silenced showed decreased osteoclast differentiation in response to IL-23 stimulation. IL-23 treatment increased the expression of miR-223 and enhanced the binding of STAT4 to the promoter of pri-miR-223. This study is the first to demonstrate that IL-23 promotes osteoclastogenesis by transcriptional regulation of miR-223 in murine macrophages and mice with CIA. Furthermore, our data indicate that LSF, a selective inhibitor of STAT4, should be an ideal therapeutic agent for treating RA through down-regulating miR-223-associated osteoclastogenesis.

The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1β stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1β, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1β stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.

Advanced knowledge of messenger RNA (mRNA) N6-methyladenosine (m6A) and DNA N6-methyldeoxyadenosine (6 mA) redefine our understanding of these epigenetic modifications. Both m6A and 6mA carry important information for gene regulation, and the corresponding catalytic enzymes sometimes belong to the same gene family and need to be distinguished. However, a comprehensive analysis of the m6A gene family in tomato remains obscure. Here, 24 putative m6A genes and their family genes in tomato were identified and renamed according to BLASTP and phylogenetic analysis. Chromosomal location, synteny, phylogenetic, and structural analyses were performed, unravelling distinct evolutionary relationships between the MT-A70, ALKBH, and YTH protein families, respectively. Most of the 24 genes had extensive tissue expression, and 9 genes could be clustered in a similar expression trend. Besides, SlYTH1 and SlYTH3A showed a different expression pattern in leaf and fruit development. Additionally, qPCR data revealed the expression variation under multiple abiotic stresses, and LC-MS/MS determination exhibited that the cold stress decreased the level of N6 2′-O dimethyladenosine (m6Am). Notably, the orthologs of newly identified single-strand DNA (ssDNA) 6mA writer–eraser–reader also existed in the tomato genome. Our study provides comprehensive information on m6A components and their family proteins in tomato and will facilitate further functional analysis of the tomato N6-methyladenosine modification genes.

Recently, we have shown that manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) conjugated with exendin-4 (Ex4) act as a contrast agent that directly trace implanted mouse islet β-cells by magnetic resonance imaging (MRI). Here we further advanced this technology to track implanted porcine neonatal pancreatic cell clusters (NPCCs) containing ducts, endocrine, and exocrine cells. NPCCs from one-day-old neonatal pigs were isolated, cultured for three days, and then incubated overnight with MnMEIO-Ex4 NPs. Binding of NPCCs and MnMEIO-Ex4 NPs was confirmed with Prussian blue staining in vitro prior to the transplantation of 2000 MnMEIO-Ex4 NP-labeled NPCCs beneath the left renal capsule of six nondiabetic nude mice. The 7.0 T MRI on recipients revealed persistent hypointense areas at implantation sites for up to 54 days. The MR signal intensity of the graft on left kidney reduced 62–88% compared to the mirror areas on the contralateral kidney. Histological studies showed colocalization of insulin/iron and SOX9/iron staining in NPCC grafts, indicating that MnMEIO-Ex4 NPs were taken up by mature β-cells and pancreatic progenitors. We conclude that MnMEIO-Ex4 NPs are excellent contrast agents for detecting and long-term monitoring implanted NPCCs by MRI.

Multi-object tracking aims to assign a uniform ID for the same target in continuous frames, which is widely used in autonomous driving, security monitoring, etc. In the previous work, the low-scoring box, which inevitably contained occluded target, was filtered by Non-Maximum Suppression (NMS) in a detection stage with a confidence threshold. In order to track occluded target effectively, in this paper, we propose a method of NMS performing later. The NMS works in tracking rather than the detection stage. More candidate boxes that contain the occluded target are reserved for trajectory matching. In addition, unrelated boxes are discarded according to the Intersection over Union (IOU) between the predicted and detected box. Furthermore, an unsupervised pre-trained person re-identification (ReID) model is applied to improve the domain adaptability. In addition, the bicubic interpolation is used to increase the resolution of low-scoring boxes. Extensive experiments on the MOT17 and MOT20 datasets have proven the effectiveness of tracking occluded targets of the proposed method, which achieves an MOTA of 78.3%.

To specifically detect and trace transplanted islet β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) with exendin-4 (Ex4) which specifically binds glucagon-like peptide-1 receptors on the surface of β-cells. The size distribution of MnMEIO and MnMEIO-Ex4 NPs were 67.8 ± 1.3 and 70.2 ± 2.3 nm and zeta potential 33.3 ± 0.5 and 0.6 ± 0.1 mV, respectively. MnMEIO and MnMEIO-Ex4 NPs with iron content ≤ 40 μg/mL did not affect MIN6 β-cell viability and insulin secretion. Positive iron staining was found in MIN6 β-cells loaded with MnMEIO-Ex4 NPs but not in those with MnMEIO NPs. A transmission electron microscope confirmed MnMEIO-Ex4 NPs were distributed in the cytoplasm of MIN6. In vitro MR images revealed a loss of signal intensity in MIN6 β-cells labeled with MnMEIO-Ex4 NPs but not with MnMEIO NPs. After transplantation of islets labeled with MnMEIO-Ex4, the graft under kidney capsule could be visualized on MRI as persistent hypointense areas up to 17 weeks. Moreover, histology of the islet graft showed positive staining for insulin, glucagon and iron. Our results indicate MnMEIO-Ex4 NPs are safe and effective for the detection and long-term monitoring of transplanted β-cells by MRI.

Coupling systems play a vital role in hydraulic power transmission equipment. In recent years, flat-face coupling systems have been extensively studied due to their environment friendly features. The difficulty of the connection process of hydraulic equipment increases with the increase in their working pressure. To improve the convenience of making high-pressure connections, a novel flat-face coupling system is proposed in this article. In the proposed design, which is based on the conventional flat-face coupling system, the resistance caused by high hydraulic fluid pressure during coupling is drastically reduced by the addition of an instantaneous pressure relief module. In this study, the theoretical model of the system kinetics is established to illustrate the operational mechanism of the novel design, and a series of computational fluid dynamics numerical investigations based on the novel dynamic mesh technology and Ansys Mosaic meshing technology are implemented to verify the rationality of the proposed design. Additionally, an optimal design of the novel flat-face coupling system is proposed to reduce the energy loss during hydraulic power transmission.

In this work we developed methylene blue-immobilized copper-iron nanoparticles (MB-CuFe NPs) through a facile one-step hydrothermal reaction to achieve a better phototherapeutic effect. The Fe/Cu ratio of the CuFe NPs was controllable by merely changing the loading amount of iron precursor concentration. The CuFe NPs could serve as a Fenton catalyst to convert hydrogen peroxide (H2O2) into reactive oxygen species (ROS), while the superparamagnetic properties also suggest magnetic resonance imaging (MRI) potential. Furthermore, the Food and Drug Administration (FDA)-approved MB photosensitizer could strongly adsorb onto the surface of CuFe NPs to facilitate the drug delivery into cells and improve the photodynamic therapy at 660 nm via significant generation of singlet oxygen species, leading to enhanced cancer cell-damaging efficacy. An MTT (thiazolyl blue tetrazolium bromide) assay proved the low cytotoxicity of the CuFe NPs to cervical cancer cells (HeLa cells), namely above 80% at 25 ppm of the sample dose. A slight dissolution of Cu and Fe ions from the CuFe NPs in an acidic environment was obtained, providing direct evidence for CuFe NPs being degradable without the risk of long-term retention in the body. Moreover, the tremendous photo-to-thermal conversion of CuFe NPs was examined, which might be combined with photodynamic therapy (PDT) for promising development in the depletion of cancer cells after a single pulse of deep-red light irradiation at high laser power.

The role of an atomic-layer thick periodic Y–O array in inducing the epitaxial growth of single-crystal hexagonal YAlO3 perovskite (H-YAP) films was studied using high-angle annular dark-field and annular bright-field scanning transmission electron microscopy in conjunction with a spherical aberration-corrected probe and in situ reflection high-energy electron diffraction. We observed the Y–O array at the interface of amorphous atomic layer deposition (ALD) sub-nano-laminated (snl) Al2O3/Y2O3 multilayers and GaAs(111)A, with the first film deposition being three cycles of ALD-Y2O3. This thin array was a seed layer for growing the H-YAP from the ALD snl multilayers with 900 °C rapid thermal annealing (RTA). The annealed film only contained H-YAP with an excellent crystallinity and an atomically sharp interface with the substrate. The initial Y–O array became the bottom layer of H-YAP, bonding with Ga, the top layer of GaAs. Using a similar ALD snl multilayer, but with the first film deposition of three ALD-Al2O3 cycles, there was no observation of a periodic atomic array at the interface. RTA of the sample to 900 °C resulted in a non-uniform film, mixing amorphous regions and island-like H-YAP domains. The results indicate that the epitaxial H-YAP was induced from the atomic-layer thick periodic Y–O array, rather than from GaAs(111)A.

Graphite felt (GF) is a multi-functional material and is widely used as electrodes of electrochemical devices for energy and environmental applications. However, due to the inherent hydrophobicity of graphite felt, it must be hydrophilically pretreated to obtain good electrochemical activity. Metal oxides coating is one of the feasible methods to modify the surface of GF, and in order to ensure that the metal oxides have a better conductivity for obtaining higher electrochemical activity, a subsequent H2 heat-treatment process is usually adopted. In this study, atomic layer deposition (ALD) is used to deposit TiO2 nanocoating on graphite felt (GF) for surface modification without any H2 thermal post-treatment. The results show that the ALD-TiO2-modified GF (ALD-TiO2/GF) owns excellent hydrophilicity. Moreover, the ALD-TiO2/GF exhibits excellent electrochemical properties of low equivalent series resistance (Rs), low charge-transfer resistance (Rct), and high electrochemical activity. It demonstrates that ALD is an applicable technique for modifying the GF surface. In addition, it can be reasonably imagined that not only TiO2 film can effectively modify the GF surface, but also other metal oxides grown by ALD with nanoscale-thickness can also obtain the same benefits. We anticipate this work to be a starting point for modifying GF surface by using ALD with metal oxides nanocoating.