Transcriptome and weighted gene co-expression network analyses reveal key genes and pathways involved in early fruit ripening in Citrus sinensis.

BACKGROUND: The fruit ripening period is an important target trait in fruit tree crop breeding programs. Thus, citrus tree breeders seek to develop extreme early ripening cultivars that allow optimization of citrus maturation periods. In this study, we explored the regulatory network involved in fruit ripening in Citrus sinensis using the 'Newhall' navel orange variety and its early-ripening mutant, 'Gannanzao'. This research will provide a basis for further research on important signaling pathways, gene functions and variety breeding of Citrus sinensis related to fruit ripening period. RESULTS: Physiological analyses suggested that early fruit ripening in 'Gannanzao' is regulated by early accumulation of abscisic acid (ABA), persistently high levels of jasmonic acid (JA), and higher sucrose content in the pericarp. Pericarp samples from 'Gannanzao' and 'Newhall' navel oranges were sampled for RNA sequencing analysis at 180, 200, and 220 days after flowering; 1430 differentially expressed genes (DEGs) were identified. Functional enrichment analysis indicated that these DEGs were mainly enriched in the plant hormone signal transduction and sugar metabolism pathways, as well as other pathways related to fruit ripening. Important DEGs associated with fruit ripening in 'Gannanzao' included genes involved in ABA and JA metabolism and signal transduction, as well as sugar metabolism. Weighted gene co-expression network analysis showed that the deep pink module had the strongest correlations with ABA content, JA content, and early ripening. Based on gene functionality and gene expression analyses of 37 genes in this module, two candidate hub genes and two ethylene response factor 13 (ERF13) genes (Cs_ont_5g000690 and Cs_ont_5g000700) were identified as key genes regulated by ABA and JA signaling. These findings will help to clarify the mechanisms that underlie early citrus fruit ripening and will lead to the development of excellent genetic resources for further breeding of extreme early-ripening varieties. CONCLUSIONS: Through analyses of the 'Newhall' navel orange cultivar and its early-ripening mutant 'Gannanzao', we identified genes involved in ABA and JA metabolism, signal transduction, and sugar metabolism that were related to fruit ripening. Among these, two ERF13 genes were inferred to be key genes in the regulation of fruit ripening. These findings provide insights into the genetic architecture related to early fruit ripening in C. sinensis.

Adhesive Nanoparticle-in-Microgel System with ROS Scavenging Capability and Hemostatic Activity for Postoperative Adhesion Prevention.

Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.

Curved Structure Regulated Single Metal Sites for Advanced Electrocatalytic Reactions.

Curved surface with defined local electronic structures and regulated surface microenvironments is significant for advanced catalytic engineering. Since single-atom catalysts are highly efficient and active, they have attracted much attention in recent years. The curvature carrier has a significant effect on the electronic structure regulation of single-atom sites, which effectively promote the catalytic efficiency. Here, the effect of the curvature structure with exposed metal atoms for catalysis is comprehensively summarized. First, the substrates with curvature features are reviewed. Second, the applications of single-atom catalysts containing curvature in a variety of different electrocatalytic reactions are discussed in depth. The impact of curvature effects in catalytic reactions is further analyzed. Finally, prospects and suggestions for their application and future development are presented. This review paves the way for the construction of high curvature-containing surface carriers, which is of great significance for single-atom catalysts development.

Atomic Molybdenum Nanomaterials for Electrocatalysis.

As a sustainable energy technology, electrocatalytic energy conversion requires electrocatalysts, which greatly motivates the exploitation of high-performance electrocatalysts based on nonprecious metals. Molybdenum-based nanomaterials have demonstrated promise as electrocatalysts because of their unique physiochemical and electronic properties. Among them, atomic Mo catalysts, also called Mo-based single-atom catalysts (Mo-SACs), have the most accessible active sites and tunable microenvironments and are thrivingly explored in various electrochemical conversion reactions. A timely review of such rapidly developing topics is necessary to provide guidance for further exploration of optimized Mo-SACs toward electrochemical energy technologies. In this review, recent advances in the synthetic strategies for Mo-SACs are highlighted, focusing on the microenvironment engineering of Mo atoms. Then, the representative achievements of their applications in various electrocatalytic reactions involving the N2, H2O, and CO2 cycles are summarized by combining experimental and computational results. Finally, prospects for the future development of Mo-SACs in electrocatalysis are provided and the key challenges that require further investigation and optimization are highlighted.

Catalysis with Two-Dimensional Metal-Organic Frameworks: Synthesis, Characterization, and Modulation.

The demand for the exploration of highly active and durable electro/photocatalysts for renewable energy conversion has experienced a significant surge in recent years. Metal-organic frameworks (MOFs), by virtue of their high porosity, large surface area, and modifiable metal centers and ligands, have gained tremendous attention and demonstrated promising prospects in electro/photocatalytic energy conversion. However, the small pore sizes and limited active sites of 3D bulk MOFs hinder their wide applications. Developing 2D MOFs with tailored thickness and large aspect ratio has emerged as an effective approach to meet these challenges, offering a high density of exposed active sites, better mechanical stability, better assembly flexibility, and shorter charge and photoexcited state transfer distances compared to 3D bulk MOFs. In this review, synthesis methods for the most up-to-date 2D MOFs are first overviewed, highlighting their respective advantages and disadvantages. Subsequently, a systematic analysis is conducted on the identification and electronic structure modulation of catalytic active sites in 2D MOFs and their applications in renewable energy conversion, including electrocatalysis and photocatalysis (electro/photocatalysis). Lastly, the current challenges and future development of 2D MOFs toward highly efficient and practical electro/photocatalysis are proposed.

Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC.

Targeted delivery of MerTK protein via cell membrane engineered nanoparticle enhances efferocytosis and attenuates atherosclerosis in diabetic ApoE-/- Mice.

BACKGROUND: Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. RESULTS: In this study, we found that diabetic ApoE-/- mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE-/- mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. CONCLUSIONS:  Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE-/- mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach.

Light-Activated Chemically Reactive Fibrous Patch Revolutionizes Wound Repair Through the Prevention of Postoperative Adhesion.

A light-activated chemically reactive fibrous patch (ChemPatch) with tissue adhesion and wound healing activity was developed for preventing postoperative peritoneal adhesion. ChemPatch was constructed by an integrative electrospinning fabrication strategy, generating multifunctional PCL-NHS fibers encapsulating antioxidant curcumin and MnO2 nanoparticles. ChemPatch exhibited excellent photothermal conversion, which not only reformed the physical state to match the tissue but also improved conjugation between ChemPatch and tissues, allowing for strong attachment. Importantly, ChemPatch possessed good antioxidant and radical scavenging activity, which protected cells in an oxidative microenvironment and improved tissue regeneration. Particularly, ChemPatch acted as a multifunctional barrier and could not only promote reepithelialization and revascularization in wound defect model but simultaneously ameliorate inflammation and prevent postoperative peritoneal adhesion in a mouse cecal defect model. Thus, ChemPatch represents a dual-active bioadhesive barrier for reducing the incidence and severity of peritoneal adhesions.

The histone acetyltransferase Mof regulates Runx2 and Osterix for osteoblast differentiation.

Osteoblast differentiation is regulated by various transcription factors, signaling molecules, and posttranslational modifiers. The histone acetyltransferase Mof (Kat8) is involved in distinct physiological processes. However, the exact role of Mof in osteoblast differentiation and growth remains unknown. Herein, we demonstrated that Mof expression with histone H4K16 acetylation increased during osteoblast differentiation. Inhibition of Mof by siRNA knockdown or small molecule inhibitor, MG149 which is a potent histone acetyltransferase inhibitor, reduced the expression level and transactivation potential of osteogenic key markers, Runx2 and Osterix, thus inhibiting osteoblast differentiation. Besides, Mof overexpression also enhanced the protein levels of Runx2 and Osterix. Mof could directly bind the promoter region of Runx2/Osterix to potentiate their mRNA levels, possibly through Mof-mediated H4K16ac to facilitate the activation of transcriptional programs. Importantly, Mof physically interacts with Runx2/Osterix for the stimulation of osteoblast differentiation. Yet, Mof knockdown showed indistinguishable effect on cell proliferation or apoptosis in MSCs and preosteoblast cells. Taken together, our results uncover Mof functioning as a novel regulator of osteoblast differentiation via the promotional effects on Runx2/Osterix and rationalize Mof as a potential therapeutic target, like possible application of inhibitor MG149 for the treatment of osteosarcoma or developing specific Mof activator to ameliorate osteoporosis.

Bisphenol A exposure induces testicular oxidative damage via FTO/m6A/Nrf2 axis during postnatal development in mice.

Bisphenol A (BPA), a commonly used plasticizer in the production of polycarbonate plastics and epoxy resins, has been shown to induce male reproductive toxicity. However, the effects of BPA exposure on early testicular development have not been thoroughly studied, and the underlying mechanism is yet to be elucidated. In the current study, neonatal male mice were exposed to BPA at 0, 0.1, and 5 mg/kg, respectively, by daily subcutaneous injection during postnatal day (PND) 1-35 to explore its effects on testicular development at PND 36 (the end of the first round of spermatogenesis). Morphological analyses showed that BPA exposure significantly induced apoptosis of testicular cells (p < 0.01 and p < 0.001) and reduced the thickness of seminiferous epithelium (p < 0.01). In addition, BPA exposure significantly decreased the total antioxidant capacity of testes and levels of transcription factor Nrf2 as well as its downstream antioxidant molecules of NQO1 and GPx-1 (p < 0.05 and p < 0.01). Furthermore, global m6A modifications of mRNAs were upregulated accompanied by declined m6A demethylase (FTO) in the testes of BPA groups (p < 0.05 and p < 0.01). MeRIP-quantitative real-time polymerase chain reaction (qPCR) demonstrated that BPA exposure markedly increased the m6A modification of Nrf2 mRNA (p < 0.05 and p < 0.01). These findings suggest that upregulation of m6A induced by inhibited FTO may be involved in BPA-induced testicular oxidative stress and developmental injury during postnatal development, which provides a new idea to reveal the mechanism underlying BPA interfering with testicular development.

Bioinspired All-in-One Three-Dimensional Dynamic CellMatrix Improves the Manufacture of Therapeutically Qualified Cells for Cell Therapy.

Despite the great promise, cell therapy still faces practical challenges because of the scarcity of a reliable cell source. Herein, a bioinspired 3D dynamic culture system (CellMatrix) with rational structure, composite and function, was developed for improving cell supply. CellMatrix was composed of unique core-shell fibers with a core of black phosphorus-incorporated fibroin and a shell of sericin, which together formed a 3D silkworm cocoon-mimicking structure via a bottom-up fabrication technique. CellMatrix not only provided optimal engineered biomimetic niche to facilitate cell growth but exhibited good photothermal conversion to dynamically regulate cell fates. Importantly, cell-CellMatrix construct could be directly implanted into defected tissues and improved tissue remodeling. Meanwhile, CellMatrix displayed good ice resistance and thermal conductivity, which maximally maintained cell viability and proliferation after the freeze-thawing process, allowing for storing precious cells and cell-CellMatrix construct. Thus, CellMatrix represents an all-in-one biomimetic platform for the culture-production-storage of therapeutically qualified cells.

Photoactive 3D-Printed Hypertensile Metamaterials for Improving Dynamic Modeling of Stem Cells.

Current three-dimensional (3D) cell culture systems mainly rely on static cell culture and lack the ability to thoroughly manage cell intrinsic behaviors and biological characteristics, leading to unsatisfied cell activity. Herein, we have developed photoactive 3D-printed hypertensile metamaterials based dynamic cell culture system (MetaFold) for guiding cell fate. MetaFold exhibited high elasticity and photothermal conversion efficiency due to its metapattern architecture and micro/nanoscale polydopamine coating, allowing for responding to mechanical and light stimulation to construct dynamic culture conditions. In addition, MetaFold possessed excellent cell adhesion capability and could promote cell viability and function under dynamic stimulation, thereby maximizing cell activity. Importantly, MetaFold could improve the differentiation efficacy of stem cells into cardiomyocytes and even their maturation, offering high-quality precious candidates for cell therapy. Therefore, we present a dual stimuli-responsive dynamic culture system, which provides a physiologically realistic environment for cell culture and biological study.

Exploration of the correlation between intestinal flora and peritoneal dialysis-related peritonitis.

BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD). Gut microbiota alterations occur in end-stage renal disease (ESRD) patients. The relationship between the gut microbiota and PD-related peritonitis (PRP) is still poorly understood. It is unclear whether the intestinal flora is involved in the pathogenesis of PRP. METHODS: We collected fecal samples from PRP patients and normal group (NG) PD patients. 16S rRNA sequencing was used to analyze the gut microbiota of PRP and NG patients while also comparing the gram-positive peritonitis (GPP), Escherichia coli peritonitis (EP) and culture-negative peritonitis (CNP) groups in the subgroup analysis. The demographic data and clinical indicators of all patients were collected. RESULTS: Seventeen PRP patients and 28 NG patients were recruited for this study. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in the microbial structure of PRP patients, where Bacteroidetes and Synergistetes were upregulated at different levels, while Bacilli and Lactobacillus were downregulated at different levels compared to levels in the NG group. In the subgroup analysis, Saccharimonadaceae was significantly increased in the GPP group compared to the EP and CNP group. In addition, decreased gene function associated with metabolic pathways was observed in PRP patients. CONCLUSIONS: Bacteroidetes and Synergistetes were the dominant orders in PRP patients. The altered composition of the gut microbiota in PRP patients provided deeper insights into the pathogenesis of PRP, and these biomarkers might be established as potential therapeutic targets that deserve further exploration.

Exploration of the correlation between intestinal flora and Escherichia coli peritoneal dialysis-related peritonitis.

BACKGROUND: Escherichia coli peritonitis (EP) is a serious complication of peritoneal dialysis (PD). Gut microbiota alterations occur in end-stage renal disease (ESRD) patients. The relationship between the gut microbiota and PD-related peritonitis is still poorly understood. It is unclear whether the intestinal flora is involved in the pathogenesis of EP. METHODS: We collected fecal samples from EP patients and normal group (NG) PD patients. 16S rRNA sequencing was used to analyze the gut microbiota of EP and NG patients. The demographic data and clinical indicators of all patients were collected. RESULTS: Six EP patients and 28 NG patients were recruited for this study. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in the microbial structure of EP patients, where Bacteroidetes and Synergistetes were upregulated at different levels, while Bacilli and Lactobacillus were downregulated at different levels compared to the NG group. Additionally, decreased gene function associated with metabolic pathways was observed in EP patients. CONCLUSIONS: The altered composition of the gut microbiota in EP patients provided deeper insights into the pathogenesis of EP, and these biomarkers might be established as potential therapeutic targets that deserve further exploration.

Toxicity evaluation, toxin screening and its intervention of the jellyfish Phacellophora camtschatica based on a combined transcriptome-proteome analysis.

BACKGROUND: The application of multi-omics technologies provides a new perspective to solve three main problems including species identification, toxin screening and effective antagonist conformation in the studies of marine toxic jellyfish. METHODS: A series of transcriptome-proteome based analysis accompanied with toxicity evaluations were performed for the ornamental jellyfish Phacellophora camtschatica. RESULTS: Through combined morphological observation and Cytochrome c oxidase subunit Ⅰ (CO1) molecular alignment, the sample jellyfish was identified as P. camtschatica. A total of 25,747 unigenes and 3058 proteins were obtained from the successfully constructed transcriptome and proteome, in which 6869 (26.68%) and 6618 (25.70%) unigenes, as well as 2536 (82.93%) and 2844 (93.00%) proteins were annotated against the databases of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively. The jellyfish displayed obvious in vivo lethal effects with significant increases of multi-organ functional indexes as well as in vitro activities. Total of 62 toxins from 120 toxin-related unigenes were screened including 16 metalloproteases, 11 phospholipases and others. Moreover, 11 toxins were further screened by using the erythrocyte model, where the zinc metalloproteinase nas-15-like (1) was the most abundant. Finally, Diltiazem greatly improved the survival rate while EDTA slightly prolonged the survival time in ICR mice. CONCLUSION: P. camtschatica is a poisonous jellyfish with diversified toxic components, in which metalloproteinase probably plays an important role in toxicities, and excessive Ca2+ entry may be the main mechanism of systemic lethal toxicity.

Transition metal nitrides for electrochemical energy applications.

Transition metal nitrides (TMNs), by virtue of their unique electronic structure, high electrical conductivity, superior chemical stability, and excellent mechanical robustness, have triggered tremendous research interest over the past decade, and showed great potential for electrochemical energy conversion and storage. However, bulk TMNs usually suffer from limited numbers of active sites and sluggish ionic kinetics, and eventually ordinary electrochemical performance. Designing nanostructured TMNs with tailored morphology and good dispersity has proved an effective strategy to address these issues, which provides a larger specific surface area, more abundant active sites, and shorter ion and mass transport distances over the bulk counterparts. Herein, the most up-to-date progress on TMN-based nanomaterials is comprehensively reviewed, focusing on geometric-structure design, electronic-structure engineering, and applications in electrochemical energy conversion and storage, including electrocatalysis, supercapacitors, and rechargeable batteries. Finally, we outline the future challenges of TMN-based nanomaterials and their possible research directions beyond electrochemical energy applications.

A Novel Luminescent "Nanochip" as a Tandem Catalytic System for Chemiluminescent Detection of Sweat Glucose.

Accurate sweat glucose detection is a promising alternative to invasive finger-prick blood tests, allowing for self-monitoring of blood glucose with good patient compliance. In this study, we have developed a tandem catalytic system, termed as a luminescent "nanochip" (LAON), which was composed of gold nanoparticles (AuNPs) and N-(aminobutyl)-N-(ethylisoluminol) (ABEI)-engineered oxygen-doped carbon nitride (O-g-C3N4), for chemiluminescent detection of sweat glucose. The LAON exhibits dual catalytic activity of glucose oxidase and peroxidase and can not only oxidize glucose to generate H2O2 but catalyze H2O2-mediated luminol chemiluminescence, resulting in sensitive detection of glucose. We identify that the LAON can precisely detect glucose with a detection limit of 0.1 µM, enabling us to measure glucose levels in different biological samples. Particularly, the LAON is capable of sensitively and accurately monitoring dynamic changes in sweat glucose during exercise. Therefore, the LAON provides an alternative approach to supersede invasive blood tests and may improve the management of diabetes mellitus.

Immediate psychological impact on nurses working at 42 government-designated hospitals during COVID-19 outbreak in China: A cross-sectional study.

BACKGROUND: During an epidemic of a novel infectious disease, frontline nurses suffer from unprecedented psychological stress. This study aimed to assess the immediate psychological impact on frontline nurses in China. METHODS: A multicenter, cross-sectional survey of frontline nurses was conducted via online questionnaires. Symptoms of depression, anxiety, somatic disorders, and suicidal ideation were evaluated. Demographic, stress, and support variables were entered into logistic regression analysis to identify the impact factors. FINDINGS: Of the 4,692 nurses who completed the survey, 9.4% (n = 442) were considered to have depressive symptoms, 8.1% (n = 379) represented anxiety, and 42.7% (n = 2,005) had somatic symptom. About 6.5% (n = 306) respondents had suicidal ideation. DISCUSSION: The study showed that the overall mental health of frontline nurses was generally poor during COVID-19 outbreak, and several impact factors associated with nurses' psychological health were identified. Further research is needed to ascertain whether training and support strategies are indeed able to mitigate psychological morbidities.

Effects of Low-Dose Ketamine on the Antidepressant Efficacy and Suicidal Ideations in Patients Undergoing Electroconvulsive Therapy.

OBJECTIVES: It remains controversial whether a subanesthetic dose of ketamine could modulate the antidepressant effect of electroconvulsive therapy (ECT) in patients with major depressive disorder. We investigated the effect of ketamine on accelerating the antidepressant efficacy of ECT. METHODS: One hundred twenty-seven patients with major depressive disorder were included in this randomized, placebo-controlled, double-blind study. The study group received 0.3 mg/kg ketamine, and the control group received an isovolumetric dose of normal saline before undergoing ECT under propofol anesthesia. The main outcome was the Hamilton Depression Rating Scale score after each ECT session. Suicidal ideation (SI) was also evaluated using the Hamilton Depression Rating Scale. The response, remission, and recurrence rates were analyzed using time-to-event analysis. RESULTS: No significant differences were found in the overall response, remission, and relapse rates between the groups (P > 0.05). The median number of ECT sessions for achieving response was 4.0 ± 0.41 in the study group and 7.0 ± 0.79 in the control group (P < 0.05). The median number of ECT sessions for achieving remission in the study and control groups was 8.0 ± 0.29 and 9.0 ± 0.48, respectively (P < 0.05). The median number of ECT sessions for achieving SI reduction in the study and control groups was 3.0 ± 0.75 and 6.0 ± 1.19, respectively (P < 0.05). CONCLUSIONS: Low-dose ketamine (0.3 mg/kg) could modulate the antidepressant efficacy of ECT via accelerating the onset of its effects and reducing the number of ECT sessions required to obtain response, remission, and SI reduction, without influencing the relapse rates in remitting patients after ECT treatment.

Synergistic Amplification of Oxidative Stress-Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF-Fe2.

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal-organic framework (MOF)-Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS-mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF-Fe2+ , but also generate an acidic microenvironment to activate a MOF-Fe2+ -based Fenton reaction. Importantly, MD@Lip promotes DCA-mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2 O2 ), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF-Fe2+ , leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome-based combination therapy of DCA and MOF-Fe2+ provides a promising oxidative stress-associated antitumor strategy for the management of malignant tumors.