Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

Tunable Gas Admission via a "Molecular Trapdoor" Mechanism in a Flexible Cationic Metal-Organic Framework Featuring 1D Channels.

Achieving high gas selectivity is challenging when dealing with gas pairs of similar size and physiochemical properties. The "molecular trapdoor" mechanism discovered in zeolites holds promise for highly selective gas adsorption separation but faces limitations like constrained pore volume and slow adsorption kinetics. To address these challenges, for the first time, a flexible metal-organic framework (MOF) featuring 1D channels and functioning as a "molecular trapdoor" material is intoduced. Extra-framework anions act as "gate-keeping" groups at the narrowest points of channels, permitting gas admissions via gate opening induced by thermal/pressure stimuli and guest interactions. Different guest molecules induce varied energy barriers for anion movement, enabling gas separation based on distinct threshold temperatures for gas admission. The flexible framework of Pytpy MOFs, featuring swelling structure with rotatable pyridine rings, facilitates faster gas adsorption than zeolite. Analyzing anion properties of Pytpy MOFs reveals a guiding principle for selecting anions to tailor threshold gas admission. This study not only overcomes the kinetic limitations related to gas admission in the "molecular trapdoor" zeolites but also underscores the potential of developing MOFs as molecular trapdoor adsorbents, providing valuable insights for designing ionic MOFs tailored to diverse gas separation applications.

Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

In Situ Plasma Polymerization of Self-Stabilized Polythiophene Enables Dendrite-Free Lithium Metal Anodes with Ultra-Long Cycle Life.

Constructing a flexible and chemically stable multifunctional layer for the lithium (Li) metal anodes is a highly effective approach to improve the uneven deposition of Li+ and suppress the dendrite growth. Herein, an organic protecting layer of polythiophene is in situ polymerized on the Li metal via plasma polymerization. Compared with the chemically polymerized thiophene (C-PTh), the plasma polymerized thiophene layer (P-PTh), with a higher Young's modulus of 8.1 GPa, shows strong structural stability due to the chemical binding of the polythiophene and Li. Moreover, the nucleophilic C─S bond of polythiophene facilitates the decomposition of Li salts in the electrolytes, promoting the formation of LiF-rich solid electrolyte interface (SEI) layers. The synergetic effect of the rigid LiF as well as the flexible PTh-Li can effectively regulate the uniform Li deposition and suppress the growth of Li dendrites during the repeated stripping-plating, enabling the Li anodes with long-cycling lifespan over 8000 h (1 mA cm-2 , 1 mAh cm-2) and 2500 h (10 mA cm-2 , 10 mAh cm-2 ). Since the plasma polymerization is facile (5-20 min) and environmentally friendly (solvent-free), this work offers a novel and promising strategy for the construction of the forthcoming generation of high-energy-density batteries.

Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

Epidural administration of large dose of opioid µ receptor agonist may impair cardiac functions and myocardial viability via desensitizing transient receptor potential vanilloid 1.

The incidence of postoperative myocardial injury remains high as the underlying pathogenesis is still unknown. The dorsal root ganglion (DRG) neurons express transient receptor potential vanilloid 1 (TRPV1) and its downstream effector, calcitonin gene-related peptide (CGRP) participating in transmitting pain signals and cardiac protection. Opioids remain a mainstay therapeutic option for moderate-to-severe pain relief clinically, as a critical component of multimodal postoperative analgesia via intravenous and epidural delivery. Evidence indicates the interaction of opioids and TRPV1 activities in DRG neurons. Here, we verify the potential impairment of myocardial viability by epidural usage of opioids in postoperative analgesia. We found that large dose of epidural morphine (50 µg) significantly worsened the cardiac performance (+dP/dtmax reduction by 11% and -dP/dtmax elevation by 24%, all P < 0.001), the myocardial infarct size (morphine vs Control, 0.54 ± 0.09 IS/AAR vs. 0.23 ± 0.06 IS/AAR, P < 0.001) and reduced CGRP in the myocardium (morphine vs. Control, 9.34 ± 2.24 pg/mg vs. 21.23 ± 4.32 pg/mg, P < 0.001), while induced definite suppression of nociception in the postoperative animals. It was demonstrated that activation of µ-opioid receptor (µ-OPR) induced desensitization of TRPV1 by attenuating phosphorylation of the channel in the dorsal root ganglion neurons, via inhibiting the accumulation of cAMP. CGRP may attenuated the buildup of ROS and the reduction of mitochondrial membrane potential in cardiomyocytes induced by hypoxia/reoxygenation. The findings of this study indicate that epidurally giving large dose of µ-OPR agonist may aggravate myocardial injury by inhibiting the activity of TRPV1/CGRP pathway.

Femtosecond Laser Combined with Hydrothermal Method to Construct Three-Dimensional Spatially Distributed Wurtzite ZnO Micro/Nanostructures to Enhance Photocatalytic Properties.

Conventional approaches employing nanopowder particles or deposition photocatalytic nanofilm materials encounter challenges such as performance instability, susceptibility to detachment, and recycling complications in practical photocatalytic scenarios. In this study, a novel fabrication strategy is proposed that uses femtosecond laser direct writing of self-sourced metal to prepare a self-supporting microstructure substrate and combines the hydrothermal method to construct a three-dimensional spatially distributed metal oxide micro/nanostructure. The obtained wurtzite ZnO micro/nanostructure has excellent wetting properties while obtaining a larger specific surface area and can achieve effective adsorption of methyl orange molecules. Moreover, the tight integration of ZnO with the surface interface of the self-sourced metal microstructure substrate will facilitate efficient charge transfer. Simultaneously, it improves the efficiency of light utilization (absorption) and the number of active sites in the photocatalytic process, ultimately leading to excellent photodegradation stability. This result provides an innovative technology solution for achieving efficient semiconductor surface-interface photocatalytic performance and stability.

Efficacy of different indocyanine green doses in fluorescent laparoscopic cholecystectomy: A prospective, randomized, double-blind trial.

BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

Design, synthesis and biological evaluation of potent epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors against resistance mutation for lung cancer treatment.

In this study, we identified a newly synthesized compound 7o with potent inhibition on EGFR primary mutants (L858R, Del19) and drug-resistant mutant T790M with nanomolar IC50 values. 7o showed strong antiproliferative effects against EGFR mutant-driven non-small cell lung cancer (NSCLC) cells such as H1975, PC-9 and HCC827, over cells expressing EGFRWT. Molecular docking was performed to investigate the possible binding modes of 7o inside the binding site of EGFRL858R/T790M and EGFRWT. Analysis of cell cycle evidenced that 7o induced cell cycle arrest in G1 phases in the EGFR mutant cells, H1975 and PC-9, which resulted in decreased S-phase populations. Moreover, compound 7o induced cancer cell apoptosis in in vitro assays. In addition, 7o inhibited cellular phosphorylation of EGFR. In vivo, oral administration of 7o caused rapid tumor regression in H1975 xenograft model. Therefore, 7o might deserve further optimization as cancer treatment agent for EGFR mutant-driven NSCLC.

Effects of ambient temperature on pediatric incident seizure: A case-crossover analysis using distributed lag non-linear models.

OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

A novel extracellular vesicles production system harnessing matrix homeostasis and macrophage reprogramming mitigates osteoarthritis.

Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Electroacupuncture Combined with Chinese Herbal Medicine, Qidong Huoluo Granule, for Amyotrophic Lateral Sclerosis: An 8-Month Case Report.

Background: Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder characterized by progressive muscle weakness and eventual paralysis, for which there is currently no curative treatment. Mainstream medical interventions primarily focus on providing supportive care. However, acupuncture offers promising avenues for alleviating symptoms and enhancing quality of life. Specific acupuncture points are targeted to address bulbar paralysis as well as paralysis affecting the upper and lower extremities. Objective: To investigate the efficacy of electroacupuncture combined with Chinese herbal medicine in delaying disease progression and alleviating symptoms of bulbar paralysis in patients with ALS. Case Presentation: A 51-year-old male presented with a 4-year and 8-month history of weakness in his left arm and both legs, accompanied by muscle cramps and diminished coordination, which had rapidly worsened over the past year. ALS was diagnosed, and the patient was initiated on oral Riluzole (50 mg) and Qidong Huoluo granule, a Chinese herbal compound, administered twice daily. Concurrently, he underwent acupuncture treatment sessions twice weekly for over 8 months. Results: Following acupuncture therapy, the patient experienced gradual stabilization of symptoms, notably improvement in swallowing function. The combination of electroacupuncture and Qidong Huoluo granule resulted in sustained clinical enhancements post-treatment, including improvements in speech, coughing, articulation, and breathing. Conclusion: Electroacupuncture therapy demonstrates the potential to slow disease progression and ameliorate symptoms of bulbar paralysis in ALS patients. However, further robust clinical research is imperative to explain the precise therapeutic role of electroacupuncture in managing this debilitating condition. Continued investigation into the efficacy and safety profile of electroacupuncture holds promise for advancing treatment modalities for ALS.

The Phosphorus-Iron Nexus: Decoding the Nutrients Interaction in Soil and Plant.

Phosphorus (P) and iron (Fe) are two essential mineral nutrients in plant growth. It is widely observed that interactions of P and Fe could influence their availability in soils and affect their homeostasis in plants, which has received significant attention in recent years. This review presents a summary of latest advances in the activation of insoluble Fe-P complexes by soil properties, microorganisms, and plants. Furthermore, we elucidate the physiological and molecular mechanisms underlying how plants adapt to Fe-P interactions. This review also discusses the current limitations and presents potential avenues for promoting sustainable agriculture through the optimization of P and Fe utilization efficiency in crops.

Orthodontic camouflage treatment of a hyperdivergent adolescent patient with anterior open bite and TMD: a case report.

BACKGROUND: In orthodontics, anterior open bite is a common malocclusion that recurs frequently. Because the causes of anterior open bite are so varied, medical professionals must create customized treatment programs for each patient based on their unique etiology. Through the lowering of the posterior teeth, closure of the anterior teeth gap, and cooperation with intermaxillary traction, the treatment plan outlined in this case study sought to achieve a stable occlusion. CASE PRESENTATION: This case report aims to describe an orthodontic camouflage treatment of a 15-year-old female patient with anterior open bite, arch width discrepancy and a history of temporomandibular joint disorder. The patient was treated with intermaxillary vertical elastics and the multiple edgewise arch wire (MEAW) approach. A satisfactory occlusion with a neutral molar relationship was attained after 29 months of orthodontic therapy. The condylography recording showed that this patient's occlusion tended to be more stable both before and after our treatment. The purpose of this case study is to provide an overview of an orthodontic camouflage treatment for a female patient, who had a history of temporomandibular joint disease, anterior open bite, and arch width disparity. CONCLUSIONS: Our results demonstrated that more attention should be paid to levelling the occlusal plane, intrusion of the molars, decompression of temporomandibular joints and the etiology factors of malocclusion during the orthodontic period for those patients with anterior open bite.

Mesojunction-Based Design Paradigm of Structural DNA Nanotechnology.

Mesojunctions were introduced as a basic type of crossover configuration in the early development of structural DNA nanotechnology. However, the investigations of self-assembly from multiple mesojunction complexes have been overlooked in comparison to their counterparts based on regular junctions. In this work, we designed standardized component strands for the construction of complex mesojunction lattices. Three typical mesojunction configurations with three and four arms were showcased in the self-assembly of 1-, 2-, and 3-dimensional lattices constructed from both a scaffold-free tiling approach and a scaffolded origami approach.

In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

A robust and flexible CRISPR/Cas9-based system for neutrophil-specific gene inactivation in zebrafish.

CRISPR/Cas9-based tissue-specific knockout techniques are essential for probing the functions of genes in embryonic development and disease using zebrafish. However, the lack of capacity to perform gene-specific rescue or live imaging in the tissue-specific knockout background has limited the utility of this approach. Here, we report a robust and flexible gateway system for tissue-specific gene inactivation in neutrophils. Using a transgenic fish line with neutrophil-restricted expression of Cas9 and ubiquitous expression of single guide (sg)RNAs targeting rac2, specific disruption of the rac2 gene in neutrophils is achieved. Transient expression of sgRNAs targeting rac2 or cdk2 in the neutrophil-restricted Cas9 line also results in significantly decreased cell motility. Re-expressing sgRNA-resistant rac2 or cdk2 genes restores neutrophil motility in the corresponding knockout background. Moreover, active Rac and force-bearing F-actins localize to both the cell front and the contracting tail during neutrophil interstitial migration in an oscillating fashion that is disrupted when rac2 is knocked out. Together, our work provides a potent tool that can be used to advance the utility of zebrafish in identifying and characterizing gene functions in a tissue-specific manner.

P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization.

BACKGROUND: Osteosarcoma is the most common malignant tumor in bone and its prognosis has reached a plateau in the past few decades. Recently, metabolic reprogramming has attracted increasing attention in the field of cancer research. In our previous study, P2RX7 has been identified as an oncogene in osteosarcoma. However, whether and how P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming remains unexplored. METHODS: We used CRISPR/Cas9 genome editing technology to establish P2RX7 knockout cell lines. Transcriptomics and metabolomics were performed to explore metabolic reprogramming in osteosarcoma. RT-PCR, western blot and immunofluorescence analyses were used to determine gene expression related to glucose metabolism. Cell cycle and apoptosis were examined by flowcytometry. The capacity of glycolysis and oxidative phosphorylation were assessed by seahorse experiments. PET/CT was carried out to assess glucose uptake in vivo. RESULTS: We demonstrated that P2RX7 significantly promotes glucose metabolism in osteosarcoma via upregulating the expression of genes related to glucose metabolism. Inhibition of glucose metabolism largely abolishes the ability of P2RX7 to promote osteosarcoma progression. Mechanistically, P2RX7 enhances c-Myc stabilization by facilitating nuclear retention and reducing ubiquitination-dependent degradation. Furthermore, P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming in a predominantly c-Myc-dependent manner. CONCLUSIONS: P2RX7 plays a key role in metabolic reprogramming and osteosarcoma progression via increasing c-Myc stability. These findings provide new evidence that P2RX7 might be a potential diagnostic and/or therapeutic target for osteosarcoma. Novel therapeutic strategies targeting metabolic reprogramming appear to hold promise for a breakthrough in the treatment of osteosarcoma.

The active Fe chelator proline-2'-deoxymugineic acid enhances peanut yield by improving soil Fe availability and plant Fe status.

Iron (Fe) deficiency restricts crop yields in calcareous soil. Thus, a novel Fe chelator, proline-2'-deoxymugineic acid (PDMA), based on the natural phytosiderophore 2'-deoxymugineic acid (DMA), was developed to solve the Fe deficiency problem. However, the effects and mechanisms of PDMA relevant to the Fe nutrition and yield of dicots grown under field conditions require further exploration. In this study, pot and field experiments with calcareous soil were conducted to investigate the effects of PDMA on the Fe nutrition and yield of peanuts. The results demonstrated that PDMA could dissolve insoluble Fe in the rhizosphere and up-regulate the expression of the yellow stripe-like family gene AhYSL1 to improve the Fe nutrition of peanut plants. Moreover, the chlorosis and growth inhibition caused by Fe deficiency were significantly diminished. Notably, under field conditions, the peanut yield and kernel micronutrient contents were promoted by PDMA application. Our results indicate that PDMA promotes the dissolution of insoluble Fe and a rich supply of Fe in the rhizosphere, increasing yields through integrated improvements in soil-plant Fe nutrition at the molecular and ecological levels. In conclusion, the efficacy of PDMA for improving the Fe nutrition and yield of peanut indicates its outstanding potential for agricultural applications.