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Hepatitis E, a significant global public health issue in China, is caused by sporadic infections with regional hepatitis E virus (HEV) genotypes 1, 3, and 4. To date, most immunoassays currently used to test human sera for the presence of anti-HEV antibodies cannot identify HEV at the genotype level. However, such information would be useful for identifying the source of infecting virus. Therefore, here we describe the development of a competitive enzyme-linked immunosorbent assay (ELISA) for detecting anti-genotype 1 HEV antibodies in human sera. Using recombinant genotype 1 HEV ORF3 protein as immunogen, traditional hybridoma technology was employed to generate seven monoclonal antibodies (mAbs), of which two mAbs specifically reacted with the immunogen. One of these two mAbs, 1D2, was labeled with horseradish peroxidase (HRP) for use in competitive ELISA (cELISA). After cELISA optimization using a checkerboard assay design, the amount of ORF3SAR−55 as coating antigen (100 ng/well), HRP-1D2 mAb concentration (1 μg/mL), and test serum dilution (1:10) were selected and a result ≥ 19.5 was used as the cutoff for a positive result. Importantly, cross-genotype cELISA results indicated that the cELISA could not detect anti-genotype 3 rabbit and 4 swine HEV antibodies. Moreover, human sera confirmed as negative for anti-HEV antibodies using the commercial ELISA kit were all negative via cELISA. However, because the commercial ELISA kit detects anti-all genotypes HEV antibodies and the cELISA only detects anti-genotype 1 HEV antibodies, the consistence rate of two assays detecting positive sera is low. In summary, here a cELISA for detecting anti-genotype 1 HEV antibodies was developed for use in epidemiological investigations of genotype 1 HEV infections in humans. • Seven mAbs were produced using genotype 1 HEV ORF3 protein as immunogen. • One mAb that specifically bound to genotype 1 HEV ORF3 protein was selected and labeled for use in a cELISA to detect anti-genotype 1 HEV antibodies. • The competitive ELISA developed here will aid clinical diagnosis of HEV infections and will be useful for large-scale serological testing of genotype 1 HEV infections in humans.

This letter presents a fixed-frequency beam-steering leaky-wave antenna (LWA) with switchable beam number. The proposed LWA consists of an impedance modulation surface (IMS) and dc bias circuit. A three-strip structure is designed as the unit cell of the IMS. In this design, varactor diodes are inserted in the unit cell and the impedance characteristics of every unit cell can be controlled independently. Both average reactance and modulation periodicity of the IMS can be tuned for leaky-wave radiation with different beam angle. The proposed LWA can be configured to work in single-beam mode or dual-beam mode. A prototype of the proposed LWA operating at 8 GHz is fabricated and measured. By controlling the dc voltages of varactor diodes, a scanning range of 118° can be achieved.

In this letter, transmitting metasurface using single dielectric substrate for orbital angular momentum (OAM) generation is presented in Ku -band. A dimension extension method is introduced in designing the unit cell of the proposed transmitting metasurface to achieve required phase shift and transmission magnitude for generating OAM. A prototype of the proposed transmitting metasurface is fabricated and measured. Measured results suggest that the proposed transmitting metasurface can generate OAM vortex wave at 18 GHz. The proposed method can be applied in wireless communication systems requiring low-profile transmitted OAM generator.

Osteosarcoma is the most common primary malignancy of the skeleton in children and adults. The outcomes of people with osteosarcomas are unsatisfied. β-Phenethyl isothiocyanate (PEITC) exhibits chemoprevention and chemotherapeutic activities against many human cancers. The molecular mechanism underlying its action on osteosarcoma is still unknown. This study was aimed at investigating the effect of PEITC on human osteosarcoma both in vitro and in vivo. The results showed that PEITC reduced cell viability, inhibited proliferation, and caused G2/M cell cycle arrest in four human osteosarcoma cell lines (MNNG/HOS, U-2 OS, MG-63, and 143B). Then, we found that PEITC altered iron metabolism related to the processes of iron import, storage, and export, which resulted in increased labile iron. Expectedly, PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation. Multiple cell death modalities, including ferroptosis, apoptosis, and autophagy, were triggered in human osteosarcoma cells. Three MAPKs (ERK, p38, and JNK) were all activated after PEITC treatment; however, they presented different responses among the four human osteosarcoma cell lines. ROS generation was proved to be the major cause of PEITC-induced decreased proliferative potential, altered iron metabolism, cell death, and activated MAPKs in human osteosarcoma cells. In addition, PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose. In conclusion, this study reveals that PEITC simultaneously triggers ferroptosis, apoptosis, and autophagy in human osteosarcoma cells by inducing oxidative stress.

Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC50 value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G2/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers.

With the widespread use of static magnetic fields (SMFs) in medicine, it is imperative to explore the biological effects of SMFs and the mechanisms underlying their effects on biological systems. The presence of magnetic materials within cells and organisms could affect various biological metabolism and processes, including stress responses, proliferation, and structural alignment. SMFs were generally found to be safe at the organ and organism levels. However. human subjects exposed to strong SMFs have reported side effects. In this review, we combined the magnetic properties of biological samples to illustrate the mechanism of action of SMFs on biological systems from a biophysical point of view. We suggest that the mechanisms of action of SMFs on biological systems mainly include the induction of electric fields and currents, generation of magnetic effects, and influence of electron spins. An electrolyte flowing in a static magnetic field generates an induced current and an electric field. Magnetomechanical effects include orientation effects upon subjecting biological samples to SMFs and movement of biological samples in strong field gradients. SMFs are thought to affect biochemical reaction rates and yields by influencing electron spin. This paper helps people how can harness the favorable biological effects of SMFs.

Long-term operation of cables and equipment under abnormal currents can cause insulation aging and reduce the service life of the equipment. Identifying the current-carrying status accurately and early detection of potential failures of power cables is particularly significant for ensuring the operation of power equipment safely and economically. This paper proposed a method for detecting the current-carrying status of power cables and an early fault warning based on temperature information. Based on the theoretical basis of the relationship between temperature and current. According to IEC 61000-3-7 and IEC 60038 standards, the current-carrying state evaluation method is analyzed and given, and the early fault warning model is established. Finally, the paper takes the cable connector and the lightning arrester in the power ring network cabinet as an example to verify the method’s feasibility. It shows that the characteristic information of the relative temperature variation curves under different current carrying states significantly differs. Includes the slope of hour 9, the slope of hour 2, and the maximum. Then the total duration under abnormal current operation is calculated, and the early warning of faults can realize.

Osteosarcoma is the most common primary bone malignancy in children and young adults, with a very poor prognosis. It is of great importance to develop targeted therapeutic strategies for osteosarcoma. Sulfasalazine (SAS) is an FDA-approved drug for the treatment of Crohn’s disease, rheumatoid arthritis, and inflammatory bowel disease. It acts as an inhibitor of cystine/glutamate system, which is important for cellular glutathione synthesis and maintenance of GPx4 activity. Nowadays, SAS has been repurposed as an antitumor drug for inducing ferroptosis in cancers. This study aimed to uncover the role of iron in SAS-induced ferroptotic cell death in K7M2 osteosarcoma cells. Herein, SAS led to an iron-dependent cell death mode in K7M2 cells, accompanied with decreased antioxidant defense and increased production of cytosolic and lipid reactive oxygen species. Results also showed that iron supplement with ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS) exacerbated the declined cell viability of SAS-treated K7M2 cells, while in the case of iron depletion, it weakened such suppression. Furthermore, iron promoted SAS-induced alterations on cell cycle, cytoskeleton, mitochondria morphology and function, and redox system. Iron also induced the dysfunction of autophagic activity in SAS-treated K7M2 cells. In conclusion, our study uncovered the essential role of iron in SAS's effects on K7M2 cells and provided the potential combined therapy of inhibition on antioxidant defense and an increase in oxidative potential, which further disturbed the redox status in tumor cells.

Objective The monitoring of anesthetic depth based on electroencephalogram derivation is not currently adjusted for age. Here we analyze the influence of age factors on electroencephalogram characteristics. Methods Frontal electroencephalogram recordings were obtained from 80 adults during routine clinical anesthesia. The characteristics of electroencephalogram with age and anesthesia were observed during four kinds of anesthesia. Results The slow wave power, δ power, Bispectral Index (BIS) and approximate entropy can be used to distinguish different states of anesthesia (P < 0.05). In the deep and very deep anesthesia states, δ power decreased with age (P < 0.0001). In the very deep anesthesia state, θ power decreased with age (P < 0.05). In the deep and very deep anesthesia states, α power decreased with age (P = 0.0002). In the light and deep anesthesia states, β power decreased with age (P = 0.003). In the deep anesthesia state, γ power decreased with age (P = 0.002). In the very deep anesthesia state, permutation entropy increased significantly with age (P = 0.0001). In the very deep anesthesia state, BIS value increased with age (P = 0.006). The slow wave power, approximate entropy, and sample entropy did not show age-dependent changes. Conclusions The influence of age should be considered when using BIS and δ power to monitor the depth of anesthesia, while the influence of age should not be considered when using slow wave power and approximate entropy to monitor the depth of anesthesia.

Hyperspectral image (HSI) classification is an important part of its processing and application. Aiming at the problems of high data dimensionality and high spatial neighborhood correlation in HSI classification, we propose a spatial-spectral joint classification method of HSI with locality and edge preserving in this article. First, the input HSI is normalized, and the feature is extracted by principal component analysis. The first principal component image is taken as the guidance image. Second, guided filtering is used to extract the spatial features of each band separately. Then, the extracted spatial features are superimposed, and low-dimensional embedding is completed through local Fisher discriminant analysis. Finally, the obtained low-dimensional embedded features are input into a random forest classifier to get classification results. The experimental results of two HSI show that the proposed method achieves higher classification accuracy than other related methods. In the case of randomly selecting 10% and 1% samples from each class of ground object as training samples, the overall classification accuracy is improved to 99.57% and 97.79%, respectively. This method effectively uses the spatial and local information of the image in low dimensional embedding, and preserves the boundaries of the ground objects, thus improving the classification effect.

Exposure to microgravity during long-term habitation in space results in numerous physiological alterations in the human body. Among them, reduction in bone mineral density is well known as one of the most important changes, which limits further space exploration by humans. Although numerous studies have been conducted on microgravity-induced bone loss, the explicit mechanism behind its occurrence has not been fully elucidated. Even though mechanical unloading has been generally accepted as a dominant cause of microgravity-induced bone loss, the risks of iron-loading and oxidative damage due to increased iron stores and dietary iron intake during spaceflight have attracted much attention, especially in bone. Indeed, excessive iron accumulation has been found in astronauts exposed to microgravity during spaceflight. Moreover, a great deal of evidence from clinical, animal, and cellular studies indicates that iron-loading has direct adverse effects on bone metabolism. This review summarizes the latest findings on bone loss and iron status in microgravity conditions, as well as the association between iron-loading and bone abnormalities. We discuss the possible mechanisms of iron overload-induced skeletal involution. Finally, we hypothesize that, in addition to mechanical unloading, iron overload due to long-term spaceflight missions is a high risk factor for microgravity-induced bone loss. The underlying mechanism by which it occurs is iron-loading that leads to an imbalance in bone remodeling, involving bone formation and bone resorption, mediated by oxidative stress via the Fenton reaction.

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.

Polyacrylate resin composite materials with the mineral exhibit super water absorbency and good degradation ability. In this work, expanded perlite and sodium polyacrylate resin composite materials have been prepared with ceric ammonium nitrate (CAN), N,N’-methylene bisacrylamide (MBA), tapioca starch, and expanded perlite. Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (SEM) are used to characterize the bonds absorption peaks and morphologies. The results suggest that the expanded perlite can graft on sodium polyacrylate resin, and the optimal distilled water and 0.9% NaCl absorbency are 1079 and 253 g/g when the expanded perlite content is 8 wt%, respectively. The swelling water model of the composite materials is firstly simulated to be Voigt-based model. In addition, the composite materials absorbency that is influenced by special characteristics of the expanded perlite has been shown.

Osteosarcoma is a common malignant bone tumor in clinical orthopedics. Iron chelators have inhibitory effects on many cancers, but their effects and mechanisms in osteosarcoma are still uncertain. Our in vitro results show that deferoxamine (DFO) and deferasirox (DFX), two iron chelators, significantly inhibited the proliferation of osteosarcoma cells (MG-63, MNNG/HOS and K7M2). The viability of osteosarcoma cells was decreased by DFO and DFX in a concentration-dependent manner. DFO and DFX generated reactive oxygen species (ROS), altered iron metabolism and triggered apoptosis in osteosarcoma cells. Iron chelator-induced apoptosis was due to the activation of the MAPK signaling pathway, with increased phosphorylation levels of JNK, p38 and ERK, and ROS generation, in this process, the expression of C-caspase-3 and C-PARP increased. In an orthotopic osteosarcoma transplantation model, iron chelators (20 mg/kg every day, Ip, for 14 days) significantly inhibited the growth of the tumor. Immunohistochemical analysis showed that iron metabolism was altered, apoptosis was promoted, and malignant proliferation was reduced with iron chelators in the tumor tissues. In conclusion, we observed that iron chelators induced apoptosis in osteosarcoma by activating the ROS-related MAPK signaling pathway. Because iron is crucial for cell proliferation, iron chelators may provide a novel therapeutic strategy for osteosarcoma.

Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing. Magnetic fields (MFs)‐based devices are translated into clinical practice for the treatment of bone diseases and neurodegenerative disorder. This review attempts to give insight into the mechanisms and applications of MFs in wound care, especially in improving the healing outcomes of diabetic wounds. First, we discuss the pathological conditions associated with chronic diabetic wounds. Next, the mechanisms involved in MFs’ effects on wounds are explored. At last, studies and reports regarding the effects of MFs on diabetic wounds from both animal experiments and clinical trials are reviewed. MFs exhibit great potential in promoting wound healing and have been practised in the management of diabetic wounds. Further studies on the exact mechanism of MFs on diabetic wounds and the development of suitable MF‐based devices could lead to their increased applications into clinical practice., The possible mechanism of the effects of MFs on diabetic wound healing.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious virus that has led to enormous economic loss worldwide because of ineffective prevention and treatment. In view of their minimized size, high target specificity and affinity, nanobodies have been extensively investigated as diagnostic tools and treatments of many diseases. Previously, a PRRSV Nsp9-specific nanobody (Nb6) was identified as a PRRSV replication inhibitor. When it was fused with cell-penetrating peptide (CPP) TAT, Nb6-TAT could enter the cells for PRRSV suppression. However, delivery of molecules by CPP lack cell specificity and have a short duration of action. PRRSV has a tropism for monocyte/macrophage lineage, which expresses high levels of Fcγ receptors. Herein, we designed a nanobody containing porcine IgG Fc (Fcγ) to inhibit PRRSV replication in PRRSV permissive cells. Fcγ fused Nb6 chimeric antibody (Nb6-pFc) was assembled into a dimer with interchain disulfide bonds and expressed in a Pichia pastoris system. The results show that Nb6-pFc exhibits a well-binding ability to recombinant Nsp9 or PRRSV-encoded Nsp9 and that FcγR-mediated endocytosis of Nb6-pFc into porcine alveolar macrophages (PAM) was in a dose-dependent manner. Nb6-pFc can inhibit PRRSV infection efficiently not only by binding with Nsp9 but also by upregulating proinflammatory cytokine production in PAM. Together, this study proposes the design of a porcine IgG Fc-fused nanobody that can enter PRRSV susceptible PAM via FcγR-mediated endocytosis and inhibit PRRSV replication. This research reveals that nanobody-Fcγ chimeric antibodies might be effective for the control and prevention of monocyte/macrophage lineage susceptible pathogeneses.

Bone loss is one of the most serious medical problem associated with prolonged weightlessness in long-term spaceflight mission. Skeletal reloading after prolonged spaceflight have indicated incomplete recovery of lost bone, which may lead to an increased risk of fractures in astronauts when returning to Earth. Substantial studies have revealed the capacity of static magnetic fields (SMFs) on treating various bone disorders, whereas it is unknown whether SMFs have the potential regulatory effects on bone quality in unloaded mice during unloading. This study was conducted to investigate the potential effects of whole-body SMF exposure with 0.2 ∼ 0.4 T on the recovery of unloading-induced bone loss. Eight‐week‐old male C57BL/6J mice were subjected to hindlimb unloading (HLU) for 4 weeks, following the mice were reloaded for 4 weeks under geomagnetic field (GMF) and SMF of 0.2 ∼ 0.4 T. Bone quality indexes, including bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, and bone mechanical properties were examined by the measurement of dual energy X-ray absorptiometry (DEXA), micro-computed tomography (Micro-CT), and 3-point bending. Bone turnover was evaluated by bone histomorphometric and serum biochemical assay. We found that SMF exposure for 4 weeks significantly promoted the recovery in HLU-induced decrease of BMD and BMC, deterioration of bone microarchitecture, and reduction of bone strength. The results from bone turnover determination revealed that SMF exposure for 4 weeks induced lower osteoclast number of trabecular bone and serum TRAP-5b levels in reloaded mice, whereas SMF showed no significant alteration in skeletal osteoblast number and serum osteocalcin levels. Together, our findings suggest that SMF of 0.2 ∼ 0.4 T facilitated the recovery of unloading-induced bone loss by inhibiting the increase of bone resorption in reloaded mice, and indicate that SMF might become a promising biophysical countermeasure for maintaining bone health in astronauts after landing.

Bone loss is one of the most serious medical problem associated with prolonged weightlessness in long-term spaceflight mission. Skeletal reloading after prolonged spaceflight have indicated incomplete recovery of lost bone, which may lead to an increased risk of fractures in astronauts when returning to Earth. Substantial studies have revealed the capacity of static magnetic fields (SMFs) on treating various bone disorders, whereas it is unknown whether SMFs have the potential regulatory effects on bone quality in unloaded mice during unloading. This study was conducted to investigate the potential effects of whole-body SMF exposure with 0.2–0.4 T on the recovery of unloading-induced bone loss. Eight‐week‐old male C57BL/6J mice were subjected to hindlimb unloading (HLU) for 4 weeks, following the mice were reloaded for 4 weeks under geomagnetic field (GMF) and SMF of 0.2–0.4 T. Bone quality indexes, including bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, and bone mechanical properties were examined by the measurement of dual energy X-ray absorptiometry (DEXA), micro-computed tomography (Micro-CT), and 3-point bending. Bone turnover was evaluated by bone histomorphometric and serum biochemical assay. We found that SMF exposure for 4 weeks significantly promoted the recovery in HLU-induced decrease of BMD and BMC, deterioration of bone microarchitecture, and reduction of bone strength. The results from bone turnover determination revealed that SMF exposure for 4 weeks induced lower osteoclast number of trabecular bone and serum TRAP-5b levels in reloaded mice, whereas SMF showed no significant alteration in skeletal osteoblast number and serum osteocalcin levels. Together, our findings suggest that SMF of 0.2–0.4 T facilitated the recovery of unloading-induced bone loss by inhibiting the increase of bone resorption in reloaded mice, and indicate that SMF might become a promising biophysical countermeasure for maintaining bone health in astronauts after landing.

With the rise of artificial intelligence, the emergence of unmanned vehicles can alleviate traffic congestion and reduce the risk of traffic accidents, in which image recognition has become one of the key technologies. Yet, with the advent of the concept of adversarial examples, many works have proved that the existence of adversarial examples has huge hidden danger in the field of scene recognition. Currently, in unmanned scene recognition, polarization images are widely used because they can robustly describe important physical properties of the object. However, most of the researches on adversarial examples are based on RGB images, and few people studied polarization-based imaging. Therefore, this paper proposes an adversarial attack with fusion of polarization for unmanned scenes. Theoretically, we analyze that polarization images have better effects on adversarial example attacks than RGB images. Experimentally, we evaluate the performance of the proposed model by generating adversarial examples attack scene recognition classification model. The experiment results show that compared with RGB images, polarization images are less vulnerable to attack and have better effects on robustness, which can improve the security of unmanned scenes. And it can reduce the successful attack rate of adversarial examples by up to 9.4%.

Background: Finding emerging strategies for new use of the “old drug-vitamin C” on cancer treatment-combined with chemotherapy drugs.Methods: This study investigates the mechanisms that pharmacological ascorbate (vitamin C, AA) mediated toxicity in osteosarcoma cells and the effects of pharmacological ascorbate combined with cisplatin (DDP) on osteosarcoma cells in vitro and in vivo.Results: Pharmacological ascorbate not only promoted the production of hydrogen peroxide (H2O2) to kill osteosarcoma cells, but also improved its lethality to tumor cells by reducing the activity of catalase (CAT). DNA damage was the primary reason leading to osteosarcoma cell death, and depletion of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), activated apoptosis-inducing factor (AIF) all contribute to ascorbate-induced toxicity. The combination of pharmacological ascorbate with cisplatin showed synergistic effect on osteosarcoma cells in vitro. Pharmacological ascorbate enhanced the efficacy of cisplatin on inhibiting osteosarcoma tumor growth in orthotopic intra-tibial mouse model.Conclusion: These results suggest that pharmacological ascorbate causes DNA damage and induces osteosarcoma cells death via H2O2 mediated-oxidative stress. The combination of pharmacological ascorbate and cisplatin has synergistic effects on osteosarcoma cells and orthotopic intra-tibial mouse model. Pharmacological ascorbate could be a safe and effective adjuvant agent against osteosarcoma tumor.

Vitamin C and iron are both important nutrients for humans and involved in several physiological processes. The biological activities of vitamin C and iron are based on their abilities to accept or donate electrons. Although vitamin C is well known as an excellent electron donor in physiological conditions, it also has pro-oxidant properties, especially with catalytic metal iron. Cancer cells have a higher iron requirement than normal cells, which allows pharmacological ascorbate to kill cancer cells selectively. In this study, we demonstrated that the levels of H2O2 in cells were significantly raised after treated with pharmacological ascorbate, and intracellular labile iron could increase pharmacological ascorbate-mediated oxidative stress by Fenton reaction. Catalytic metal iron plays opposite roles in and outside cells. Intracellular excess labile iron improved ascorbate-induced toxicity, while the excess labile iron in the medium abolished ascorbate-induced toxicity. Fe3+ and Fe2+ have the same effect on ascorbate-induced toxicity, but Fe3+ chelator deferoxamine (DFO) has a profound inhibition effect than Fe2+ chelator 2,2'-bipyridyl (BIP) on ascorbate-induced toxicity. The influence of intracellular labile iron and ascorbate on the ferritin expression may cause selective sensitivity in osteosarcoma cell lines on pharmacological ascorbate. High iron requirement of many cancer cells facilitates pharmacological ascorbate on cancer treatment. In addition, increasing iron content in tumour tissue may be effective strategies to improve the effects of pharmacological ascorbate.

The labile iron pool (LIP) is a pool of chelatable and redox-active iron, not only essential for a wide variety of metabolic process, but also as a catalyst in the Fenton reaction, causing the release of hazardous reactive oxygen species (ROS) with potential for inducing oxidative stress and cell damage. The cellular LIP represents the entirety of every heterogenous sub-pool of iron, not only present in the cytosol, but also in mitochondria, lysosomes and the nucleus, which have all been detected and characterized by various fluorescent methods. Accumulated evidence indicates that alterations in the intracellular LIP can substantially contribute to a variety of injurious processes and initiate pathological development. Herein, we present our understanding of the role of the cellular LIP. To fully review the LIP, firstly, the significance of cellular labile iron in different subcellular compartments is presented. And then, the trafficking processes of cellular labile iron between/in cytosol, mitochondria and lysosomes are discussed in detail. Then, the recent progress in uncovering and assessing the cellular LIP by fluorescent methods have been noted. Overall, this summary may help to comprehensively envision the important physiological and pathological roles of the LIP and shed light on profiling the LIP in a real-time and nondestructive manner with fluorescent methods. Undoubtedly, with the advent and development of iron biology, a better understanding of iron, especially the LIP, may also enhance treatments for iron-related diseases.