Intracellular Energy Supply Research Articles

Markers of intracellular energy supply under conditions of hypoxia in premature babies

Markers of intracellular energy supply under conditions of hypoxia in premature babies

H2O2 Self‐Supplied Chemodynamic Nanosystem Enhanced by Ca2+ Interference and Starvation Strategy for Targeted Cancer Therapy

AbstractChemodynamic therapy (CDT) has received increasing attention in recent years due to its effectiveness and specificity. However, the limited endogenous hydrogen peroxide (H2O2) concentration and resistance to reactive oxygen species in cancer cells hinder the further application of CDT. Here, an H2O2 self‐supplied nanosystem FCaO2@ZIF‐67‐2‐DG‐FA (FZDF) is synthesized to achieve efficient CDT improvement by Ca2+ overload and starvation therapy. Under folic acid‐mediated tumor targeting and endocytosis, the ZIF‐67 layer of FZDF is cleaved in the mildly acidic environment, releasing Co2+ and 2‐deoxy‐D‐glucose (2‐DG). The decomposition of exposed FCaO2 generates sufficient H2O2, which further produces abundant •OH via the Fenton‐like reaction of Co2+. Simultaneously, Ca2+ overload‐triggered mitochondrial dysfunction couples with glycolysis inhibition via 2‐DG‐induced starvation, which disrupts intracellular adenosine triphosphate (ATP) synthesis and amplifies the efficacy of CDT. Silicon nanoparticles released from FCaO2 are applied as in vitro fluorescent probes to image tumor cells overexpressing folate receptors. The results have presented that FZDF can actively accumulate in tumor cells, causing the mitochondrial membrane potential abnormality and a decrease in intracellular ATP content, thereby enhancing the self‐supplied CDT with less effect on normal cells and tissues. This work provides a novel strategy for constructing effective CDT nanosystems by hindering intracellular energy supply.

Expanding the understanding of Volvariella volvacea autolysis at 4°C with transcriptomics and metabolomics

Volvariella volvacea is a type of high-temperature edible fungus that is prone to low-temperature autolysis, which makes postharvest storage and long-distance transportation difficult. In this study, transcriptomics integrated with metabolomics analysis provided the profiling of genes and metabolites in V. volvacea fruiting bodies stored at 4 °C. According to the transcriptomics and metabolomics analysis, 1613 and 1846 differentially expressed genes, 126 and 136 differential metabolites were identified at 12 h and 24 h compared to control (0 h), respectively. 6 common metabolic pathways were found by integrated analysis, of which starch and sucrose metabolism and pyruvate metabolism were further analyzed. The results exhibited that low-temperature autolysis was the consequence of the intracellular and extracellular interactions. Expression changes of genes (CEL2, CEL3, CEL6B and GH5–1) involved in cellulose metabolism led to the degradation of cellular structure. The rapid reduction of soluble sugar resulted in a decrease in the cytoplasmic concentration and an increase in osmotic potential, thereby liquefying the surface of fruiting bodies. The differential metabolites and genes of malate metabolism participated in the electron supply of the electron transport chain, but long-term low temperature made the intracellular energy supply insufficient, causing cold damage. This study provides a theoretical basis for further understanding in the mechanisms of low-temperature autolysis of V. volvacea.

Hypoxia stress alters gene expression in the gills and spleen of greater amberjack (Serioladumerili)

Greater amberjack (Seriola dumerili) is a fish species that has significant economic and cultural value. It has a large size and grows rapidly. However, the intolerance to hypoxia poses a major obstacle to the growth of its aquaculture industry. This study focuses on the gills and spleen, two organs closely associated with the response to acute hypoxic stress. By simulating the acute hypoxic environment and using Illumina RNA-Seq technology, we explored the gills and spleen transcriptome changes in the acute hypoxia intolerant and tolerant groups of greater amberjack. It was discovered that gill tissues in the tolerant group may maintain a stable intracellular energy supply by promoting glycolysis and β-oxidation compared to the intolerant group. Additionally, it promotes angiogenesis, enhances the ability to absorb dissolved oxygen, and accelerates oxygen transport to the mitochondria, adapting to the hypoxic environment. Anti-apoptotic genes were up-regulated in gill tissues in the tolerant group compared to the intolerant group, thereby minimizing the damage of acute hypoxia. On the other hand, the spleen inhibited the TCA and energy-consuming lipid synthesis pathways to supply energy under acute hypoxic stress. Pro-angiogenic genes were down-regulated in the spleen of individuals in the tolerant group compared to the intolerant group, which may be related to organ function. The suppressed reactive oxygen species (ROS) production and the impaired immune response function of the spleen were also found. The study explored the acute hypoxic stress response in greater amberjack and the molecular mechanisms underlying its tolerance to acute hypoxia.

A four-in-one multifunctional self-assembly hydrogel composed of natural drugs for repairing myocardial infarction

To meet the multiple demands of myocardial repair, it would be a novel strategy for myocardial repair if multiple drugs could be constructed into an integrated multifunctional drug formulation. In this study, four drugs with different functions (thioctic acid with antioxidant effects, quercetin with anti-inflammatory and antioxidant effects, arginine with pro-angiogenic effects, and Mn2+ with imaging functions) were selected to construct a four-in-one injectable hydrogel (thioctic acid-arginine-quercetin-Mn2+) through chemical bonding and supramolecular interactions. First, thioctic acid polymerized to a redox-sensitive degradable polymer—poly(thioctic acid) containing disulfide bonds in the main chains through ring-opening polymerization. Quercetin was conjugated to the main chain of the poly(thioctic acid) molecules via thiyl radical-polyphenol Michael addition. Arginine cross-linked the carboxyl groups side chains of the poly(thioctic acid) molecules through hydrogen bonding. Mn2+ further cross-linked the carboxyl groups' side chains of the poly(thioctic acid) molecules through ionic bonding. The hydrogel has antioxidant properties, promotes neovascularization, inhibits inflammatory, improves intracellular Ca2+ overload and mitochondrial dysfunction, protects adenosine triphosphatase (ATPase) activity, and maintains intracellular energy supply, which can reduce the size of myocardial infarcts, and improves cardiac function. This construction method of preparing integrated multifunctional hydrogels from natural drugs will provide a new therapeutic strategy for myocardial repair.

Rapid Adaptability and Regulation of Physiological Status of Lager Yeast Ensure Its Activity During Dehydration

Yeast products either active dry yeast or liquid yeast are used for beer brewing. Dry yeast offers advantages over liquid yeast, including longer shelf life, easier storage and transportation, convenient usage. While active dry lager yeast now has gained popularity in Chinese breweries, lacking knowledge about yeast physiology status during drying process hinders the customizing dry yeast for specific requirements. This study delved into the dehydration process of two lager yeasts G03 and M14 used in Chinese breweries and one commercial yeast W34/70. W34/70 with greater desiccation resistance exhibiting rapid adaptation during drying process maintained highest intracellular adenosine-5′-triphosphate (ATP). Improved accumulation of antioxidants including glutathione and trehalose, as well as complementary synthesis of chitin in cell wall attributed to the desiccation resistance of yeasts. Higher intracellular energy supply and anti-oxidative capacity of yeast strain facilitated the balanced reactive oxygen species (ROS) accumulation. Together with an effective DNA synthesis and cell replication, more cells would survive after dehydration and subsequent rehydration. Current study provides new evidence for the theory of yeast desiccation resistance and further help with preparation of active dry yeast products.

Molecular mechanisms of mitochondria-mediated ferroptosis: a potential target for antimalarial interventions.

Ferroptosis is an iron-dependent form of regulated cell death characterized by glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation, and the build-up of lipotoxic reactive species. Ferroptosis-targeted induction is a promising therapeutic approach for addressing antimalarial drug resistance. In addition to being the primary source of intracellular energy supply and reactive oxygen species (ROS) generation, mitochondria actively participate in diverse forms of regulated cell death, including ferroptosis. Altered mitochondrial morphology and functionality are attributed to ferroptosis. Diverse mitochondria-related proteins and metabolic activities have been implicated in fine-tuning the action of ferroptosis inducers. Herein, we review recent progress in this evolving field, elucidating the numerous mechanisms by which mitochondria regulate ferroptosis and giving an insight into the role of the organelle in ferroptosis. Additionally, we present an overview of how mitochondria contribute to ferroptosis in malaria. Furthermore, we attempt to shed light on an inclusive perspective on how targeting malaria parasites' mitochondrion and attacking redox homeostasis is anticipated to induce ferroptosis-mediated antiparasitic effects.

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

Energy metabolism of the immune system : Consequences in chronic inflammation

Energy is the currency of life. The systemic and intracellular energy metabolism plays an essential role for the energy supply of the resting and activated immune system and this also applies to chronic inflammatory diseases. This presentation examines both components of the systemic and cellular energy metabolism in health and chronic inflammation. Aliterature search was conducted using PubMed, Embase and the Cochrane Library. The information is presented in the form of anarrative review. Achronically activated immune system acquires large amounts of energy-rich substrates that are lost for other functions of the body. In particular, the immune system and the brain are in competition. The consequences of this competition are many known diseases, such as fatigue, anxiety, depression, anorexia, sleep problems, sarcopenia, osteoporosis, insulin resistance, hypertension and others. The permanent change in the brain causes long-term alterations that stimulate disease sequelae even after disease remission. In the intracellular energy supply, chronic inflammation typically involves a conversion to glycolysis (to lactate, which has its own regulatory functions) and the pentose phosphate pathway in disorders of mitochondrial function. The chronic changes in immune cells of patients with rheumatoid arthritis (RA) lead to adisruption of the citric acid cycle (Krebs cycle). The hypoxic situation in the inflamed tissue stimulates many alterations. A differentiation is made between effector functions and regulatory functions of immune cells. Based on the energy changes mentioned, novel treatment suggestions can be made in addition to those already known in energy metabolism.

A Mitochondria-Targeted Ferroptosis Inducer Activated by Glutathione-Responsive Imaging and Depletion for Triple Negative Breast Cancer Theranostics.

Ferroptosis is a new type of iron-dependent programmed cell death characterized by glutathione (GSH) depletion, selenoprotein glutathione peroxidase 4 (GPX4) inactivation, and lipid peroxides accumulation. Mitochondria, as the main source of intracellular energy supply and reactive oxygen species (ROS) generation, play a central role in oxidative phosphorylation and redox homeostasis. Therefore, targeting cancer-cell mitochondria and attacking redox homeostasis is expected to induce robust ferroptosis-mediated anticancer effects. In this work, a theranostic ferroptosis inducer (IR780-SPhF), which can simultaneously achieve the imaging and therapy of triple-negative breast cancer (TNBC) by targeting mitochondria is presented. It is developed from a mitochondria-targeting small molecule (IR780) with cancer-preferential accumulation, enabling it to react with GSH by nucleophilic substitution, resulting in mitochondrial GSH depletion and redox imbalance. More interestingly, IR780-SPhF exhibits GSH-responsive near-infrared fluorescence emission and photoacoustic imaging characteristics, further facilitating diagnosis and treatment with real-time monitoring of TNBC with a highly elevated GSH level. Both in vitro and in vivo results demonstrate that IR780-SPhF exhibits potent anticancer effect, which is significantly stronger than cyclophosphamide, a classic drug commonly recommended for TNBC patients in clinic. Hence, the reported mitochondria-targeted ferroptosis inducer may represent a promising candidate and a prospective strategy for efficient cancer treatment.

Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.

As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic-co-glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.

Pre-exposure to Fe2O3 or TiO2 Nanoparticles Inhibits Subsequent Biological Uptake of 55Fe-Labeled Fe2O3 Nanoparticles

Aquatic organisms are frequently exposed to various nanoparticles (NPs) in the natural environment. Thus, studies of NP bioaccumulation should include organisms that have been previously exposed to NPs. Our study investigated the effects of pre-exposure of Tetrahymena thermophila (T. thermophila) to Fe2O3 or TiO2 NPs on the protozoan's subsequent uptake of 55Fe-labeled Fe2O3 (55Fe2O3) NPs. Molecular mechanisms underlying the pre-exposure effects were explored in transcriptomic and metabolomic experiments. Pre-exposure to either NPs inhibited the subsequent uptake of 55Fe2O3 NPs. The results of the transcriptomic experiment indicated that NP pre-exposure influenced the expression of genes related to phagosomes and lysosomes and physiological processes such as glutathione and lipid metabolism, which are closely associated with the endocytosis of 55Fe2O3 NPs. The differentially expressed metabolites obtained from the metabolomic experiments showed an enrichment of energy metabolism and antioxidation pathways in T. thermophila pre-exposed to NPs. Together, these results demonstrate that the pre-exposure of T. thermophila to Fe2O3 or TiO2 NPs inhibited the protozoan's subsequent uptake of 55Fe2O3 NPs, possibly by mechanisms involving the alteration of endocytosis-related organelles, the induction of oxidative stress, and a lowering of the intracellular energy supply. Thus, NP pre-exposure represents a scenario which can inform increasingly realistic estimates of NP bioaccumulation.

Defect-Rich Ni-CoO@PEG Porous Hexagonal Nanosheets: Multi-enzyme and Ultrasound Catalysis for Synergistic Anticancer Treatment.

Given the similarity with photocatalysis, sonodynamic therapy (SDT) can be defined as ultrasonic (US) catalysis. Encouraged by the principles of photocatalysis and defect chemistry, defect-rich nickel (Ni)-doped cobaltous oxide (Ni-CoO@PEG) porous hexagonal nanosheets have been synthesized as a sonosensitizer. The doping of Ni decreases the band gap that is testified by density functional theory to increase the US-generated charges. Under US irradiation, Ni-CoO@PEG nanosheets produce 1O2 as an active species that is determined by dissolved O2 and electrons. Moreover, the doping also brings abundant oxygen vacancies (OV) that not only are in favor of efficient separation of electron-hole but also enhance the interaction toward O2, boosting 1O2 generation. In addition, Ni-CoO@PEG shows robust mimic catalase (CAT) and peroxidase characterization to effectively improve the intratumor O2 content and oxidation stress. What is more, the nanosheets also possess glucose oxidase activity that can consume glucose to elevate the H2O2/acid level and to block the intracellular energy supply. The tandem nanozyme behaviors would further regulate the tumor microenvironment for assisting anticancer treatment. It is noted that Ni-CoO@PEG reveals a novel half-metallic feature endowing great magnetism and magnetic resonance imaging capacity. The above synergistic treatments exhibit outstanding anticancer performance that also evokes antitumor immunity to suppress metastasis and recurrence, efficiently.

Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases.

As an organelle essential for intracellular energy supply, mitochondria are involved in intracellular metabolism and inflammation, and cell death. The interaction of mitochondria with the NLRP3 inflammasome in the development of lung diseases has been extensively studied. However, the exact mechanism by which mitochondria mediate the activation of the NLRP3 inflammasome and trigger lung disease is still unclear. The literatures related to mitochondrial stress, NLRP3 inflammasome and lung diseases were searched in PubMed. This review aims to provide new insights into the recently discovered mitochondrial regulation of the NLRP3 inflammasome in lung diseases. It also describes the crucial roles of mitochondrial autophagy, long noncoding RNA, micro RNA, altered mitochondrial membrane potential, cell membrane receptors, and ion channels in mitochondrial stress and regulation of the NLRP3 inflammasome, in addition to the reduction of mitochondrial stress by nuclear factor erythroid 2-related factor 2 (Nrf2). The effective components of potential drugs for the treatment of lung diseases under this mechanism are also summarized. This review provides a resource for the discovery of new therapeutic mechanisms and suggests ideas for the development of new therapeutic drugs, thus promoting the rapid treatment of lung diseases.

Nucleolar stress: Molecular mechanisms and related human diseases.

Ribosome biogenesis in the nucleolus is an important process that consumes 80% of a cell's intracellular energy supply. Disruption of this process results in nucleolar stress, triggering the activation of molecular systems that respond to this stress to maintain homeostasis. Although nucleolar stress was originally thought to be caused solely by abnormalities of ribosomal RNA (rRNA) and ribosomal proteins (RPs), an accumulating body of more current evidence suggests that many other factors, including the DNA damage response and oncogenic stress, are also involved in nucleolar stress response signaling. Cells reacting to nucleolar stress undergo cell cycle arrest or programmed death, mainly driven by activation of the tumor suppressor p53. This observation has nominated nucleolar stress as a promising target for cancer therapy. However, paradoxically, some RP mutations have also been implicated in cancer initiation and progression, necessitating caution. In this article, we summarize recent findings on the molecular mechanisms of nucleolar stress and the human ribosomal diseases and cancers that arise in its wake.

Regulation of Cell Wall Degradation and Energy Metabolism for Maintaining Shelf Quality of Blueberry by Short-Term 1-Methylcyclopropene Treatment

In order to study a short-term and efficient technology by 1-methylcyclopropene (1-MCP) in blueberry, the fruit was treated with 0, 0.5, 1 and 3 μL/L 1-MCP for 2 h then stored at 25 ± 1 °C with 40–50% relative humidity (RH) for 9 d. The weight loss, decay incidence, respiration rate, firmness, soluble solid content (SSC), titratable acid (TA), Brix-acid ratio (BAR), sensory evaluation, content of cell wall polysaccharide, activities of cell wall composition-related enzymes and energy metabolism in blueberry were determined during shelf life. The results showed that the weight loss, decay incidence and respiration rate were reduced by 3 μL/L 1-MCP treatment. Compared to other groups, the firmness, the content of TA and anthocyanins were maintained in 3 μL/L 1-MCP-treated blueberry. In contrast, the SSC and BAR were lower compared to those untreated. However, the sensory evaluation of “taste” and “aroma” value showed no differences in all fruits. The content of protopectin, cellulose and hemicellulose was higher in 1-MCP-treated blueberry, accompanied by a decrease in polygalacturonase (PG) and pectin methyl esterase (PME) activity. The content of water-soluble pectin (WSP) was lower in 1-MCP-treated blueberry than untreated ones. The activity of phenylalanine ammonia lyase (PAL), peroxidase (POD), cinnamyl alcohol dehydrogenase (CAD) and 4-coumarate-CoA ligase (4CL) was higher in 1-MCP-treated blueberry than the untreated, which induced more serious lignification. The results of energy metabolism also showed that the 1-MCP treatment could ensure sufficient intracellular energy supply. The 3 μL/L 1-MCP treatment could maintain the shelf quality and retard decomposition of cell wall polysaccharide by ensuring sufficient intracellular energy supply and inhibiting cell wall-degrading enzymes activity. Taken together, this study highlighted an efficient and short-term 1-MCP treatment technique.

Metabolic reprogramming and alteration of the redox state in hyper-productive MDCK cells for influenza a virus production

Influenza is a global public health issue leading to widespread morbidity and mortality with devastating economic loss annually. Madin-Darby Canine Kidney (MDCK) cell line has been a major cell line for influenza vaccine applications. Though many details of the host metabolic responses upon influenza A virus (IAV) infection have been documented, little is known about the metabolic reprogramming features of a hyper-productive host for IAV vaccine production. In this study, a MDCK cell clone H1 was shown to have a particular high productivity of 30 × 103 virions/cell. The glucose and amino acid metabolism of H1 were evaluated, indicating that the high producer had a particular metabolic reprogramming phenotype compared to its parental cell line (P): elevated glucose uptake, superior tricarboxylic acid cycle flux, moderate amino acid consumption, and better regulation of reactive oxygen species. Combined with the stronger mitochondrial function and mild antiviral and inflammatory responses characterized previously, our results indicated that the high producer had a sufficient intracellular energy supply, and balanced substrate distribution for IAV and host protein synthesis as well as the intracellular redox status. Understanding of these metabolic alterations paves the way for the rational cell line development and reasonable process optimization for high-yield influenza vaccine production.

Evaluation of enhancing effect of soybean oil on polymalic acid production by Aureobasidium pullulans HA-4D.

Polymalic acid (PMA) is a water-soluble polyester produced by Aureobasidium pullulans. In this study, the physiological response of A. pullulans after the addition of vegetable oils was investigated. Soybean oil (SBO) is pivotal for shortening fermentation time and achieving high PMA titer. With the addition of 1% (w/v) SBO, the titer and productivity of PMA was, respectively, increased by 34.2% and 80%. SBO acted as a chemical stimulatory agent rather than a carbon source, the enhancement on PMA production was attributed to the component of fatty acid. SBO induced the dimorphism (yeast-like cells and mycelia) of A. pullulans, in vitro enzyme activities indicated that the TCA oxidative branch for malic acid synthesis might be strengthened, which could generate more ATP for PMA synthesis, and the assay of intracellular energy supply validated this deduction. This study provided a new sight for recognizing the regulatory behavior of SBO in A. pullulans.

Melatonin Alleviates Chilling Injury Symptom Development in Mango Fruit by Maintaining Intracellular Energy and Cell Wall and Membrane Stability.

The efficacy of the signaling molecule melatonin for alleviating chilling injury (CI) in mango (Mangifera indica L.) fruit was studied to investigate the potential role of membrane integrity, energy charge, and ripening-related changes in the development of CI, and its management by melatonin. ‘Langra’ and ‘Gulab Jamun’ cultivar mango fruit was immersed in 100 μM of melatonin before storage for 28 days at 5°C with weekly transfers to shelf life at 25°C. CI symptom development was associated with compositional and enzymatic aspects of textural changes, cell membrane deterioration, and chemical energy status. Melatonin-treated ‘Langra’ fruit exhibited very low CI (5 vs. 21%) while ‘Gulab Jamun’ fruit exhibited higher CI (36 vs. 38%) during 28 days of storage at 5 ± 1°C. Higher chilling tolerance in melatonin-treated ‘Langra’ was associated with lower softening, ascribed to lower cell wall degrading exo- and endo-polygalacturonase, pectinesterase, and endo-1,4-β-D-glucanase. In addition, lower membrane deteriorating-phospholipase D and lipoxygenase activity in melatonin-treated ‘Langra’ corresponded to lower palmitic and stearic acids and higher oleic, linoleic, and linolenic acids accumulation, thus, higher unsaturated/saturated fatty acids ratio. Additionally, there was a higher intracellular energy supply with melatonin, represented by a higher adenylate energy charge (AEC) arising from higher ATP and ADP and lower AMP accumulation, related to higher H+-ATPase, Ca2+-ATPase, succinate dehydrogenase, and cytochrome c oxidase activities. This study for the first time provides evidence, suggesting that melatonin alleviation of CI is related to the preservation of membrane integrity, thereby protecting the intracellular energy supply, and preserving cell wall integrity via impeding cell wall degrading enzyme activities.

NIR-II sensitive Co9S8/S-CDs@PEG nanocomposites with enhanced multi-enzyme mediated phototherapy

Here, Co9S8/S-CDs@PEG (CSCs@PEG) nanocomposites are synthesized by a two-step hydrothermal process. Firstly, sulfur-doped carbon dots (S-CDs) are prepared by using 3-mercaptopropionic acid as a precursor. A region with denser –SH group is regarded as nucleation site on S-CDs for the growth of Co9S8 to induce heterostructure. As-synthesized CSCs@PEG possess great harvest in NIR region and hyperthermia (51.5%, 1064 nm) for photothermal (PTT). Besides, hyperthermia can elevate the thermal energy of nanocomposite to assist low-energy NIR-II irradiation (1064 nm, 1.16 eV), realizing the excitation of Co9S8 (1.46 eV) and reactive oxygen species (ROS) generation for photodynamic therapy (PDT). What's more, CSCs@PEG exhibits GOx-like activity that could consume glucose to elevate H2O2 level and inhibit intracellular energy supply. In addition, they also show mimic peroxidase (POD) and catalase (CAT) characterization, and the tandem multi-nanozye activities endue the enhanced chemotherapy (CDT) and PDT. CSCs@PEG reveals the greater ROS generation and nanozyme activity compared with pure Co9S8@PEG, attributing to the efficient charge separation in heterostructure. The novel biodegradation of CSCs@PEG makes the elimination via feces and urine within 2 weeks. That is associated with PTT/PDT/CDT/starvation therapy to activate immune response for anticancer.