Inspirational Story of Agriculture at Living with The Land Attraction at EPCOT.

Since its debut in 1982, The Land has embodied Walt Disney's vision, capturing the attention of millions of EPCOT guests with venues focusing on agriculture and environmental stewardship and sustainability. The Land pavilion spans over eight acres in the World Nature section of EPCOT at the Walt Disney World Resort in Lake Buena Vista, Florida. The pavilion houses three attractions, namely Soarin' Around the World, Awesome Planet, and the Living with The Land boat ride, complemented by a greenhouse walking tour entitled Behind the Seeds and two restaurants. Each attraction derives inspiration from nature and challenges mankind to be responsible stewards of planet earth. This feature article focuses on the Living with The Land boat ride attraction, which traverses greenhouses showcasing agricultural technologies and crops from around the world. The sections below describe both how various show elements are designed to engage guests and how the show is made possible by applying relevant science and technology.

Fe3O4 Nanoparticles Embedded into Pyridinic-N-Rich Carbon Nanohoneycomb with Strong dx2-Pz Orbital Hybridization for High-Performance Electromagnetic Wave Absorption.

Carbon-based magnetic nanocomposites as promising lightweight electromagnetic wave (EMW) absorbents are expected to address critical issues caused by electromagnetic pollution. Herein, Fe3O4 nanoparticles embedded into a 3D N-rich porous carbon nanohoneycomb (Fe3O4@NC) were developed via the pyrolysis of an in-situ-polymerized compound of m-phenylenediamine initiated by FeCl2 in the presence of NaCl crystals as templates. Results demonstrate that Fe3O4@NC features highly dispersed Fe3O4 nanoparticles into an ultrahigh specific pyridinic-N doping carbon matrix, resulting in excellent impedance matching characteristics and electromagnetic wave absorbing capability with the biggest effective absorption bandwidth (EAB) of up to 7.1 GHz and the minimum reflective loss (RLmin) of up to -65.5 dB in the thin thickness of 2.5 and 2.3 mm, respectively, which also outperforms the majority of carbon-based absorbers reported. Meanwhile, its high absorption performance is further demonstrated by an ethylene propylene diene monomer wave absorbing patch filled with 8.0 wt % Fe3O4@NC, which can completely shield a 5G signal in a mobile phone. In addition, theory calculation reveals that there is a strongest dx2-Pz orbital hybridization interaction between Fe3O4 clusters and pyridinic-N dopants in the carbon network, compared with other kinds of N dopants, which can not only generate more dipoles of carbon networks but also increase net magnetic moments of Fe3O4, thereby leading to a coupling effect of efficient dielectric and magnetic losses. This work provides new insights into the precise design and synthesis of carbon-based magnetic composites with specific interface interactions and morphological effects for high-efficiency EMW absorption materials.

The N545S and K717N substitution at the N-glycosylation sites of the S2 subunit of avian infectious bronchitis virus can significantly enhance viral pathogenicity.

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

1,25-Dihydroxyvitamin D3 reduces early mortality post severe burn injury via alleviating endotoxemia, oxidative stress and inflammation.

Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.

Experimental study on migration characteristics of LNAPL in the aquitard under pumping conditions.

Research on the migration behaviors of contaminants in the aquitard has been deficient for an extended period. Clay is commonly employed as an impermeable layer or barrier to stop the migration of contaminants. However, under certain conditions, the clay layer may exhibit permeability to water, thereby allowing contaminants to infiltrate and potentially contaminate adjacent aquifers. Consequently, it holds immense importance to scrutinize and investigate the migration characteristics of light non-aqueous phase liquid (LNAPL) within the aquitard for the purposes of groundwater pollution control and remediation. To evaluate the environmental risk posed by organic contaminants in the aquitard, an experimental model was formulated and devised to monitor the LNAPL concentration in the aquitard under pumping conditions. The correlation between pumping rate and LNAPL concentration was investigated. A self-developed plexiglass sandbox model was used to simulate the migration characteristics of LNAPL in the aquitard under pumping conditions. Four experimental scenarios were designed, varying pumping rates, aquitard thicknesses, and groundwater level changes. The LNAPL concentration curve was derived by systematically tracking and analyzing LNAPL levels at various locations within the aquitard. The results indicated that higher pumping rates corresponded to increased migration of LNAPL, resulting in greater LNAPL ingress into the pumping well during extraction. A thicker aquitard demonstrated a more pronounced inhibitory effect on LNAPL, leading to an extended penetration time of LNAPL within the aquitard. The drawdown within the aquitard exerted a discernible influence on LNAPL migration, with the LNAPL concentration continuing to decrease in tandem with declining water levels during pumping. These research findings can establish a scientific foundation for the control and remediation of contaminants within aquitards.

[Material basis and mechanism of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" based on UHPLC-Q-Exactive Orbitrap HRMS coupled with network pharmacology and molecular docking].

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer.

Nowadays in our society, lung cancer is exhibiting a high mortality rate and threat to human health. Conventional diagnostic techniques used in the field of lung cancer often necessitate the use of extensive instrumentation, exhibit a tendency for false positives, and are not suitable for widespread early screening purposes. Conventional approaches to treat lung cancer primarily involve surgery, chemotherapy, and radiotherapy. However, these broad-spectrum treatments suffer from drawbacks such as imprecise targeting and significant side effects, which restrict their widespread use. Metal-organic frameworks (MOFs) have attracted significant attention in the diagnosis and treatment of lung cancer owing to their tunable electronic properties and structures and potential applications. These porous nanomaterials are formed through the intricate assembly of metal centers and organic ligands, resulting in highly versatile frameworks. Compared to traditional diagnostic and therapeutic modalities, MOFs can improve the sensitivity of lung cancer biomarker detection in the diagnosis of lung cancer. In terms of treatment, they can significantly reduce side effects and improve therapeutic efficacy. Hence, this perspective provides an overview concerning the advancements made in the field of MOFs as potent biosensors for lung cancer biomarkers. It also delves into the latest research dealing with the use of MOFs as carriers for drug delivery. Additionally, it explores the applications of MOFs in various therapeutic approaches, including chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy. Furthermore, this review comprehensively analyses potential applications of MOFs as biosensors in the field of lung cancer diagnosis and combines different therapeutic approaches aiming for enhanced therapeutic efficacy. It also presents a concise overview of the existing obstacles, aiming to pave the way for future advancements in lung cancer diagnosis and treatment.

Anterior cervical discectomy and fusion with zero-profile anchored spacer versus plate and cage for three-level contiguous cervical degenerative disease: A systematic review and meta-analysis.

OBJECTIVE: To compare the safety, clinical outcomes and radiological results of anterior cervical discectomy and fusion (ACDF) with zero-profile anchored spacer (ZPAS) versus plate and cage (PC) for three-level contiguous cervical degenerative disease (CDD). METHODS: The study was registered at PROSPERO (CRD42024512706). The Web of Science core collection, PubMed and Embase were searched up to February 12, 2024. Review Manager 5.3 was used. The relative risk (RR) and 95% confidence interval (CI) was evaluated for dichotomous data. Continuous data were assessed using the mean difference (MD) and 95% CI. RESULTS: Nine studies comparing ACDF with ZPAS versus PC for three-level contiguous CDD were included. The intraoperative blood loss and operation time in ZPAS were significantly less than those in PC. The subsidence rate, loss of cervical alignment, fusion segmental height and intervertebral disc height were significantly greater in ZPAS than in PC. The cervical alignment and dysphagia rate within 6 months were significantly lower in ZPAS than in PC. The ASD of ZPAS was significantly lower than that of PC according to the sensitivity analysis when one study was excluded. No significant differences were identified in the other aspects. CONCLUSION: Both ACDF with ZPAS and PC were safe and effective procedures. PC was associated with increased surgical trauma. The ZPAS could better decrease the incidence of ASD and dysphagia. ZPAS was also accompanied by high subsidence rate and poor cervical alignment.

Multiomic meta-analysis suggests a correlation between steroid hormone-related genes and litter size in goats.

Litter size is a key indicator of production performance in livestock. However, its genetic basis in goats remains poorly understood. In this work, a genome-wide selection sweep analysis (GWSA) on 100 published goat genomes with different litter rates was performed for the first time to identify candidate genes related to kidding rate. This analysis was combined with the public RNA-sequencing data of ovary tissues (follicular phase) from high- and low-yielding goats. A total of 2278 genes were identified by GWSA. Most of these genes were enriched in signaling pathways related to ovarian follicle development and hormone secretion. Moreover, 208 differentially expressed genes between groups were obtained from the ovaries of goats with different litter sizes. These genes were substantially enriched in the cholesterol and steroid synthesis signaling pathways. Meanwhile, the weighted gene co-expression network was used to perform modular analysis of differentially expressed genes. The results showed that seven modules were reconstructed, of which one module showed a very strong correlation with litter size (r = -0.51 and p-value <0.001). There were 51 genes in this module, and 39 hub genes were screened by Pearson's correlation coefficient between core genes > 0.4, correlation coefficient between module members > 0.80 and intra-module connectivity ≥5. Finally, based on the results of GWSA and hub gene Venn analysis, seven key genes (ACSS2, HECW2, KDR, LHCGR, NAMPT, PTGFR and TFPI) were found to be associated with steroid synthesis and follicle growth development. This work contributes to understanding of the genetic basis of goat litter size and provides theoretical support for goat molecular breeding.

Exploring optimal incubation conditions and characteristics of methane oxidizing organisms in deep-sea environments.

Anaerobic methanotrophic archaea (ANME) play key roles in buffering the methane budget in the deep-sea environment. This study aimed to explore the optimal environmental conditions for ANME enrichment. The result showed that the sample at 10.5 MPa contained the largest copy numbers of methyl-coenzyme M reductase alpha subunit (mcrA) gene (1.1 × 106 copies/g) compared to any other pressures and the sample at 4 °C contained higher mcrA gene (1.6 × 106 copies/g) than other temperatures. The optimal enrichment pressure for ANME-2c is 10.5 MPa at 4 °C, with an optimal subsequent incubation for ANME-2c less than 211th days. Moreover, the beta nearest taxon index was significantly correlated with the incubation time (P<0.05). Total inorganic carbon and sulfate ion were key environmental factors driving community construction. This study offers insights into how ANME-2c was enriched and how species coexist in shared habitats during enrichment.

Inflammatory bowel disease and risk for hemorrhoids: a Mendelian randomization analysis.

Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.39 × 10-4) and 1.02 (95% CIs 1.01-1.03, P = 4.99 × 10-5) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.12 × 10-6) and 1.02 (95% CIs 1.01-1.02, P = 3.78 × 10-5) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01-1.03, P = 4.65 × 10-3), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P > 0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.

Searching for the optimal precondition procedure for mesenchymal stem/stromal cell treatment: Facts and perspectives.

Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li et al explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.

Uptake of zinc from the soil to the wheat grain: Nonlinear process prediction based on artificial neural network and geochemical data.

Trace elements in plants primarily derive from soils, subsequently influencing human health through the food chain. Therefore, it is essential to understand the relationship of trace elements between plants and soils. Since trace elements from soils absorbed by plants is a nonlinear process, traditional multiple linear regression (MLR) models failed to provide accurate predictions. Zinc (Zn) was chosen as the objective element in this case. Using soil geochemical data, artificial neural networks (ANN) were utilized to develop predictive models that accurately estimated Zn content within wheat grains. A total of 4036 topsoil samples and 73 paired rhizosphere soil-wheat samples were collected for the simulation study. Through Pearson correlation analysis, the total content of elements (TCEs) of Fe, Mn, Zn, and P, as well as the available content of elements (ACEs) of B, Mo, N, and Fe, were significantly correlated with the Zn bioaccumulation factor (BAF). Upon comparison, ANN models outperformed MLR models in terms of prediction accuracy. Notably, the predictive performance using ACEs as input factors was better than that using TCEs. To improve the accuracy, a two-step model was established through multiple testing. Firstly, ACEs in the soil were predicted using TCEs and properties of the rhizosphere soil as input factors. Secondly, the Zn BAF in grains was predicted using ACE as input factors. Consequently, the content of Zn in wheat grains corresponding to 4036 topsoil samples was predicted. Results showed that 85.69 % of the land was suitable for cultivating Zn-rich wheat. This finding offers a more accurate method to predict the uptake of trace elements from soils to grains, which helps to warn about abnormal levels in grains and prevent potential health risks.

Threshold effects between caffeine intake and urine flow rate: a population-based cross-sectional study.

PURPOSE: The potential benefits of caffeine intake are currently receiving much attention and exploration. Urine flow rate (UFR) is an objective index to comprehensively reflect bladder function. The aim of this study was to investigate the association between caffeine intake and UFR using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: 14,142 participants were enrolled in this study. Weighted multivariate adjusted regression models were used to explore the relationship between caffeine intake and UFR. The dose-response relationships were explored using a restricted cubic spline (RCS) and a threshold effect analysis was conducted based on the inflection points identified by the two-segment linear regression model. In addition, subgroup analysis and sensitivity analysis were applied. RESULTS: The findings suggested that the intake of caffeine was correlated with improved UFR [Model 3: 0.091 (0.057, 0.126), P value < 0.001]. In addition, the RCS supported a nonlinear relationship between them. The analysis of threshold effect further revealed a specific level of caffeine intake (34.51 mg/day) that exhibited a significant enhancement in UFR. Finally, through re-analyzing the data set obtained after multiple imputation (MI), we obtained similar results. CONCLUSION: This study found a nonlinear beneficial relationship between caffeine intake and UFR, and revealed the recommended intake of caffeine. The values varied by gender, race, education, and smoking status.

Water mediated redox-neutral cleavage of arylalkenes via photoredox catalysis.

Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting Csp2=Csp2 bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area. In this study, we introduce a redox-neutral approach for deleting a Csp2 carbon unit from substituted arylalkenes, resulting in the formation of an arene (reduction) and a carbonyl product (oxidation). This transformation is believed to proceed through a mechanistic sequence involving visible-light-promoted anti-Markovnikov hydration, followed by photoredox cleavage of Csp3-Csp3 bond in the alcohol intermediate. A crucial consideration in this design is addressing the compatibility between the highly reactive oxy radical species in the latter step and the required hydrogen-atom-transfer (HAT) reagent for both steps. We found that ethyl thioglycolate serves as the optimal hydrogen-atom shuttle, offering remarkable chemoselectivity among multiple potential HAT events in this transformation. By using D2O, we successfully prepared dideuteromethylated (-CD2H) arenes with good heavy atom enrichment. This work presents a redox-neutral alternative for alkene deconstruction, with considerable potential in late-stage modification of complex molecules.

Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design.

Previous studies have confirmed that intervertebral disc degeneration (IDD) is closely associated with inflammation-induced reactive oxygen species (ROS) and resultant cell mitochondrial membrane potential (MMP) decline. Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline. Additionally, re-energizing the mitochondria damaged in the inflammatory milieu to restore their function, is equally important. Herein, we proposed an interesting concept of mitochondrion-engine equipped with coolant, which enables first to "cool-down" the inflammatory environment, next to restore the MMP, finally to allow cells to regain normal energy metabolism through materials design. As such, we developed a multi-functional composite composed of a reactive oxygen species (ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane (TPU) scaffold. The TPU scaffold was coated with conductive polypyrrole (PPy) to electrophoretically deposit l-arginine, which could upregulate the Mammalian target of rapamycin (mTOR) pathway, thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair. While the ROS-responsive hydrogel acting as the "mito-engine coolant" could scavenge the excessive ROS to create a favorable environment for IVD cells recovery. Demonstrated by in vitro and in vivo evaluations, the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress. Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair. This unique bioinspired design integrated biomaterial science with mitochondrial biology, presents a promising paradigm for IDD treatment.

The Convergence of Sonodynamic Therapy and Cuproptosis in the Dual-Responsive Biomimetic CytoNano for Precision Mitochondrial Intervention in Cancer Treatment.

The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, "CytoNano", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano's ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.