Unexpected ubiquity of heart-shaped scale morphotype in Centroplasthelida (Haptista): Ancestral trait or multiple acquisitions?

Centrohelids (Haptista: Centroplasthelida) are axopodial protists with a remarkable diversity of external siliceous scale morphologies. It is believed that the last common ancestor of centrohelids had a double layer of siliceous scales composed of plate scales closer to a cell surface and spine scales radiating outwards. The characteristic morphotype of spine scales with a heart-shaped base was once believed to be a unique feature of the genus Choanocystis, as it was defined by Siemensma and Roijackers (1988). Further research revealed that this morphology is present in different and sometimes distantly related lineages: Ozanamiidae, Meringosphaeridae, and Marophryidae. Here, we report the fourth clade, Pterocystidae, which is also revealed to contain representatives having this phenotype. Cernunnos gen. nov. is erected here to place Cernunnos uralica sp. nov., Cernunnos arctica sp. nov., Cernunnos america sp. nov., and Cernunnos antarctica Tikhonenkov et Mylnikov, 2010, Gerasimova comb. nov. C. uralica was studied with scanning electron microscopy and SSU rDNA sequencing. Molecular phylogenetic analysis placed it into marine environmental clade P within Pterocystida. The ubiquity of spine scales with heart-shaped bases could be an example of parallel evolution, but taking into account the considerable similarity it is likely an ancestral trait, acquired from the last common ancestor of centrohelids.

Macrophage Dysfunction in Autoimmune Rheumatic Diseases and Atherosclerosis.

One of the problems of modern medical science is cardiovascular pathology caused by atherosclerotic vascular lesions in patients with autoimmune rheumatic diseases (ARDs). The similarity between the mechanisms of the immunopathogenesis of ARD and chronic low-grade inflammation in atherosclerosis draws attention. According to modern concepts, chronic inflammation associated with uncontrolled activation of both innate and acquired immunity plays a fundamental role in all stages of ARDs and atherosclerotic processes. Macrophage monocytes play an important role among the numerous immune cells and mediators involved in the immunopathogenesis of both ARDs and atherosclerosis. An imbalance between M1-like and M2-like macrophages is considered one of the causes of ARDs. The study of a key pathogenetic factor in the development of autoimmune and atherosclerotic inflammation-activated monocyte/macrophages will deepen the knowledge of chronic inflammation pathogenesis.

Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases.

In addition to identifying the major B- and T-cell subpopulations involved in autoimmune rheumatic diseases (ARDs), in recent years special attention has been paid to studying the expression of their activation markers and immune checkpoints (ICPs). The activation markers on B and T cells are a consequence of the immune response, and these molecules are considered as sensitive specific markers of ARD activity and as promising targets for immunotherapy. ICPs regulate the activation of the immune response by preventing the initiation of autoimmune processes, and they modulate it by reducing immune cell-induced organ and tissue damage. The article considers the possible correlation of ICPs with the activity of ARDs, the efficacy of specific ARD treatments, and the prospects for the use of activation molecules and activation/blocking ICPs for the treatment of ARDs.

Towards Zebrafish Models of CNS Channelopathies.

Channelopathies are a large group of systemic disorders whose pathogenesis is associated with dysfunctional ion channels. Aberrant transmembrane transport of K+, Na+, Ca2+ and Cl- by these channels in the brain induces central nervous system (CNS) channelopathies, most commonly including epilepsy, but also migraine, as well as various movement and psychiatric disorders. Animal models are a useful tool for studying pathogenesis of a wide range of brain disorders, including channelopathies. Complementing multiple well-established rodent models, the zebrafish (Danio rerio) has become a popular translational model organism for neurobiology, psychopharmacology and toxicology research, and for probing mechanisms underlying CNS pathogenesis. Here, we discuss current prospects and challenges of developing genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish.

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds-A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes.

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship "structure-antioxidant properties" was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

Multiple Euryhaline Lineages of Centrohelids (Haptista: Centroplasthelida) in Inland Saline Waters Revealed with Metabarcoding.

The diversity of centrohelids in inland saline waters was studied with metabarcoding for the first time. The fragment of V6-V7 regions of 18S rDNA was sequenced with newly designed primers. Obtained OTUs were identified with molecular phylogenetic analysis and comparison of the signatures in 39es9 hairpin of V7. The obtained data included some OTUs, which could be attributed to four described species, but the majority belonged to previously established or novel environmental clades. Along with some presumably marine/brackish clades and freshwater/low salinity (0-2 ppt) clades, seven presumable species demonstrating broad (from 1-2 up to 78 ppt) salinity tolerance were detected. A number of OTUs belonged to Raphidocystis contractilis, which is known from three independent findings in brackish habitats only. Thus, it was assumed that this species is stenohaline and specifically adapted to salinity 5-15 ppt. The high level of salinity tolerance was suggested for centrohelids before based on morphology, which was used to justify their cosmopolitan distribution. Later these views were criticized based on environmental sequencing, but the results of the current survey indicate, that at least some species are present at salinities from almost freshwater (1-2 ppt) to twice oceanic (78 ppt) and are presumably capable of overcoming oceanic salinity barriers for their distribution.

The antioxidant screening of potential materials for drugs based on 6-nitro-1,2,4-triazoloazines containing natural polyphenol fragments.

The course of viral diseases is accompanied by excessive generation of active oxygen metabolites, so the effectiveness of treatment can be improved by combining antiviral and antioxidant therapy. There was a screening of antioxidant properties of 6-nitro-1,2,4-triazoloazine-modified fragments of natural polyphenols (catechol, pyrogallol, phloroglucinol, resorcinol) which are potential dual-action combination preparations. Screening was carried out using various approaches: the study of redox transformations by cyclic voltammetry, determination of antioxidant capacity with oxidizing agents of a radical and non-radical nature by the potentiometric method using potassium hexacyanoferrate (III) and optical methods (the Folin assay and the DPPH assay). It has been established that molecules obtained by conjugation of polyphenols with heterocycles exhibit antioxidant properties. The exception is adducts of triazolodiazines with resorcinol. A decrease in the antioxidant ability of synthesized adducts relative to initial polyphenols has been noted. The antioxidant capacity has been studied at a number of temperatures (25 °C, 37 °C), and the reaction half-life has been determined. The correlation of antioxidant capacity by a potentiometric assay with the Folin assay was R = 0.71; by a potentiometric assay with the DPPH assay was R = 0.67. Leader compounds have been identified. Graphical abstract.

Noninvasive Testing for Diagnosis of Stable Coronary Artery Disease in the Elderly.

Efficient diagnostic approaches to detect coronary artery disease (CAD) in elderly patients are necessary to ensure optimal and timely treatment. The population of suspected CAD patients older than 70 years is especially vulnerable and constantly growing. Finding the optimal diagnostic approach is challenging due to certain features of this population, such as high prevalence of comorbidities, existing contraindications to exercise tests or cognitive decline, which hinders correct assessment of the patient's situation. Moreover, some symptoms of CAD can have variable significance in the elderly compared to younger adult groups. In this review, we present current recommendations of the United States (US) and European cardiologists' associations and discuss their applicability for diagnostics in the elderly population. Exercise electrocardiogram (ECG) and exercise stress echocardiography (SE) tests are not feasible for a substantial proportion of elderly patients. Coronary computed tomography angiography (CTA) appears to be an attractive alternative for such patients, but is not universally applicable; for instance, it is problematic in patients with significant calcification of the vessels. Moreover, more studies are needed to compare the results delivered by CTA to those of other diagnostic methods. Future efforts should be focused on comparative studies to better understand the limits and advantages of different diagnostic methods and their combinations. It is possible that some of the currently used diagnostic criteria could be improved to better accommodate the needs of the elderly population.

Sialylated Immunoglobulins for the Treatment of Immuno-Inflammatory Diseases.

Immunoglobulins are the potent effector proteins of the humoral immune response. In the course of evolution, immunoglobulins have formed extremely diverse types of molecular structures with antigen-recognizing, antigen-binding, and effector functions embedded in a single molecule. Polysaccharide moiety of immunoglobulins plays the essential role in immunoglobulin functioning. There is growing evidence that the carbohydrate composition of immunoglobulin-linked glycans, and especially their terminal sialic acid residues, provide a key effect on the effector functions of immunoglobulins. Possibly, sialylation of Fc glycan is a common mechanism of IgG anti-inflammatory action in vivo. Thus, the post-translational modification (glycosylation) of immunoglobulins opens up significant possibilities in the diagnosis of both immunological and inflammatory disorders and in their therapies. This review is focused on the analysis of glycosylation of immunoglobulins, which can be a promising addition to improve existing strategies for the diagnosis and treatment of various immuno-inflammatory diseases.

Study of Antioxidant Properties of Agents from the Perspective of Their Action Mechanisms.

The creation and analysis of a large variety of existing methods for the evaluation of integrated antioxidant properties are quite relevant in connection with a range of biological mechanisms of the antioxidants (AO) action. In this work, the existing methods are correlated with mechanisms of antioxidant action. It is shown that the results obtained by various methods are mainly incomparable. This can be connected with the implementation of various mechanisms of antioxidant action in methods. The analysis of the literature data presented in this review indicates the difficulty of creating a universal method and the feasibility of using integrated approaches based on the use of several methods that implement and combine various mechanisms of the chemical conversion of antioxidants. This review describes methods for studying the chelating ability of antioxidants, except for methods based on electron and hydrogen atom transfer reactions, which are currently not widely covered in modern literature. With the description of each mechanism, special attention is paid to electrochemical methods, as the interaction of active oxygen metabolites of radical and non-radical nature with antioxidants has an electron/proton/donor-acceptor nature, which corresponds to the nature of electrochemical methods and suggests that they can be used to study the interaction.

Pinjata ruminata gen. et sp. n.-A New Member of Centrohelid Family Yogsothothidae (Haptista: Centroplasthelida) from the Brackish River.

A new genus and species of centrohelid heliozoan Pinjata ruminata from the Tuzlukkol' River (Orenburg Region of Russia) and Gor'koe Lake (Chelyabinsk Region of Russia) is studied with light- and electron microscopy. Pinjata ruminata has two types of plate scales, partially running up the sides of the axopodia. Inner plate scales (3.2-4.9 × 1.5-2.6 µm) are flat, ovate-oblong and have a broad axial thickening and a thin electron-dense border. Outer plate scales (4.2-6.7 × 1.5-3.0 µm) are concave, elongated, of irregular shape, often curved, and broadened towards one end. Roundish depressions are forming two rows on both sides of the narrow axial thickening. The cells are attached to the substratum. Molecular phylogenetic analysis based on the SSU rDNA robustly placed P. ruminata in the family Yogsothothidae. This position is confirmed with the presence of five panacanthocystid increase regions. The morphology of the new genus is in a good accordance with diagnosis of the family. The status of a genus "Heteroraphidiophrys" is discussed. Other potential findings of Pinjata from literature are analyzed. Pinjata represents the third lineage of centrohelids, characterized with the presence of only tangentially oriented plate scales. The halophilic nature of Yogsothothidae is suggested.

Inhibition of Cortical Activity and Apoptosis Caused by Ethanol in Neonatal Rats In Vivo.

Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder, which includes neuroapoptosis and neurobehavioral deficits. The neuroapoptotic effects of alcohol have been hypothesized to involve suppression of brain activity. However, in vitro studies suggest that ethanol acts as a potent stimulant of cortical activity. We explored the effects of alcohol (1-6 g/kg) on electrical activity in the rat somatosensory cortex in vivo at postnatal days P1-23 and compared them with its apoptotic actions. At P4-7, when the peak of alcohol-induced apoptosis was observed, alcohol strongly suppressed spontaneous gamma and spindle-bursts and almost completely silenced neurons in a dose-dependent manner. The dose-dependence of suppression of neuronal activity strongly correlated with the alcohol-induced neuroapoptosis. Alcohol also profoundly inhibited sensory-evoked bursts and suppressed motor activity, a physiological trigger of cortical activity bursts in newborns. The suppressive effects of ethanol on neuronal activity waned during the second and third postnatal weeks, when instead of silencing the cortex, alcohol evoked delta-wave electrographic activity. Thus, the effects of alcohol on brain activity are strongly age-dependent, and during the first postnatal week alcohol profoundly inhibits brain activity. Our findings suggest that the adverse effects of alcohol in the developing brain involve suppression of neuronal activity.

A New Species of Centrohelid Heliozoan Acanthocystis amura n. sp. Isolated From Two Remote Locations in Russia.

A new species of centrohelid heliozoan Acanthocystis amura from the Amur River, the Far East of Russia was studied with light- and electron microscopy. Acanthocystis amura has simple oval plate scales (1.2-2.6 × 1.0-1.8 µm) with an axial thickening and a thin border as well as two types of spine scales. The spine scales of type 1 were 1.3-4.8 µm long and had four small hooks on their tips. The spine scales of type 2 were shorter, 1.0-3.6 µm long and had four teeth at the distal end. The morphology of A. amura resembles that of Acanthocystis quadrifurca. They both have similar spine scales but their plate scales are completely different. Acanthocystis valdiviense differs from the new species in absence of hook-bearing scales. Molecular phylogeny based on 18S rDNA consistently placed A. amura into Acanthocystis nichollsi/Acanthocystis costata clade, but relationships between those three species were not resolved. Morphology of another centrohelid strain from another location (the South Urals) has been compared with that of the original strain and few minor differences in size characteristics of the scales have been revealed.

Inflammatory Response of Monocytes/Macrophages in Patients with Systemic Sclerosis.

BACKGROUND: Investigation of the inflammatory response of immune cells is a current focus of research on autoimmune disorders. The aim of this study was to evaluate the inflammatory status of monocytes/macrophages in systemic sclerosis (SSc). METHODS: The study included 35 SSc and 25 healthy participants. The secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA) in primary cultures of monocytes/macrophages after stimulation with lipopolysaccharide (LPS) on day 1 and on day 6 of incubation. Impaired tolerance of the immune response was characterized by increased secretion of the inflammatory mediators in response to restimulation. RESULTS: Basal secretion of all cytokines was significantly higher in SSc patients compared to healthy individuals. The secretion of TNF-α, IL-1ß and IL-6 after the initial LPS stimulation, and secretion of IL-1ß, MCP-1, IL-6, IL-8 after LPS restimulation, was significantly higher in the SSc group. Eleven SSc patients (31%) showed impaired immune tolerance in terms of MCP-1 secretion. These patients were significantly younger and had a higher level of anti-topoisomerase I (anti-Scl70) antibodies compared to SSc patients with immune tolerance. CONCLUSIONS: This study revealed pro-inflammatory activation and impaired immune tolerance in monocytes/macrophages from SSc patients. The violation of immune response in terms of MCP-1 secretion may be an important factor in the development of chronic inflammation in SSc. MCP-1 may thus be a potential therapeutic target for novel SSc treatment strategies.

Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals.

This work presents a new method using kinetic potentiometry to study the thermodynamic and kinetic parameters of the reactions of antioxidants with peroxyl radicals. The rate constants of the reaction of antioxidants with radicals have been determined, and the groups of "fast" and "slow" antioxidants have been conventionally distinguished. Fast antioxidants include ascorbic, uric, gallic, chlorogenic, caffeic acids, glutathione, L-cysteine, and catechol with constant values from (1.05-9.25) × 103 M·s-1; "slow" antioxidants are α-tocopherol (in aqueous media), ionol, 2,6-ditretbutylphenol, and compounds of the azoloazine series, modified with polyphenolic fragments, with constant values from (4.00-8.50) × 102 M·s-1. It is shown that the value of the rate constant is directly related to the type of kinetic dependence of the potential recorded when an antioxidant is introduced into the solution of the radical initiator. It is shown that the method with the determination of the induction period is difficult in the study of "slow" antioxidants. It has been established that the area above the curve of the kinetic dependence Exp(∆E) is directly related to the amount of inhibited peroxyl radicals and can be used to assess the inhibitory properties of an antioxidant from a thermodynamic point of view. "Fixed time method" and "Initial rate method" were used. Positive correlations between the described method have been established. The utility of the parameter of the area above the curve of the kinetic dependence Exp(∆E) in the study of objects of complex composition is shown.

Subclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis at Low Cardiovascular Risk.

OBJECTIVE: To evaluate the rate of subclinical carotid atherosclerosis and clinical significance of immunoinflammatory markers in patients with rheumatoid arthritis (RA) at low cardiovascular risk. MATERIALS AND METHODS: The study included 275 RA patients and a control group of 100 participants without autoimmune diseases. All study participants were at low cardiovascular risk, calculated by the QRISK3 scale (<20%), and free of cardiovascular disease. Ultrasound examination of carotid arteries was performed to measure cIMT and to detect atherosclerotic plaques (ASP) in carotid arteries. sIСАМ-1, sVСАМ, and sCD40L levels were determined by enzyme immunoassay. RESULTS: Carotid ASP was observed more frequently in RA patients (27%) than in the control group (17%), p = 0.03. The frequency of ASP in RA patients did not depend on the disease's stage or activity. There was a significant correlation between cIMT and age, cardiovascular risk determined by QRISK3, level of total cholesterol, LDL, and blood pressure in RA patients, p < 0.05 in all cases. No correlation between cIMT and blood levels of sCD40L, sVCAM, and sICAM was found. In RA patients, a higher concentration of sVCAM was detected in the carotid ASP group compared to the non-atherosclerotic group. sCD40L was associated with cIMT and total cholesterol in the ASP group and with total cholesterol and blood pressure in non-atherosclerotic patients. CONCLUSIONS: Subclinical atherosclerotic lesions of the carotid arteries were observed significantly more frequently in RA patients with low cardiovascular risk than in the control group. The results of the study demonstrate the association between cIMT, traditional cardiovascular risk factors, and immunoinflammatory markers in RA patients.

Systemic Sclerosis and Atherosclerosis: Potential Cellular Biomarkers and Mechanisms.

Systemic sclerosis (SSc) is a rare systemic autoimmune disease of unknown etiology, which is characterized by endothelial dysfunction, pathologic vasculopathy, and increased tissue fibrosis. Traditionally, SSc has been regarded as a prototypical fibrotic disease in the family of systemic autoimmune diseases. Traditionally, emphasis has been placed on the three components of the pathogenesis of SSc: vascular, immune, and mesenchymal. Microvascular lesions, including endothelial dysfunction and smooth muscle cell migration into the intima of vessels in SSc, resemble the atherosclerotic process. Although microvascular disease is a hallmark of SSc, understanding the role of atherosclerotic vascular lesions in patients with SSc remains limited. It is still unknown whether the increased cardiovascular risk in SSc is related to specific cardiac complications (such as myocardial fibrosis) or the accelerated development of atherosclerosis. Different immune cell types appear to be involved in the immunopathogenesis of SSc via the activation of other immune cells, fibrosis, or vascular damage. Macrophages, B cells, T cells, dendritic cells, neutrophils, and endothelial cells have been reported to play the most important role in the pathogenesis of SSc and atherosclerosis. In our article, we reviewed the most significant and recent studies on the pathogenetic links between the development of SSc and the atherosclerotic process.

Mitochondrial DNA copy number in patients with systemic sclerosis.

Introduction: Systemic scleroderma (SSc) is a chronic autoimmune disease of inflammatory origin. Mitochondrial dysfunction is considered as an important mechanism in the pathogenesis of SSc. Currently mitochondrial DNA (mtDNA) copy number is used as a surrogate marker of mitochondrial dysfunction. Previous studies demonstrate that innate immune cells are important participants in inflammatory and fibrotic processes in SSc. The aim of the study was to evaluate the number of mtDNA copies in CD14+ monocytes and whole blood of patients with SSc in comparison with healthy individuals. Methods: Absolute mtDNA copy number was measured using digital PCR. It was found that the number of mtDNA copies in CD14+ monocytes was significantly higher in patients with SSc compared to control, while the number of mtDNA copies in the whole blood did not have significant differences. Results: The correlation analysis revealed an inverse association of mtDNA copy number with disease duration and the relationship between pro-inflammatory activation of CD14+ monocytes in terms of LPS-stimulated IL-6 secretion and mtDNA copy number. At the same time, basal and LPS-stimulated secretion of IL-6 by cultured CD+ monocytes were significantly higher in SSc group in comparison with control. Discussion: The study results suggest that increase of mtDNA copy number in CD14+ monocytes is a possible mechanism to maintain the reduced function of defective mitochondria in monocytes from patients with SSc associated with the development and progression of SSc.

Behavioral profile of adult zebrafish acutely exposed to a selective dopamine uptake inhibitor, GBR 12909.

BACKGROUND: The dopamine transporter (DAT) is the main regulator of dopamine concentration in the extrasynaptic space. The pharmacological inhibition of the DAT results in a wide spectrum of behavioral manifestations, which have been identified so far in a limited number of species, mostly in rodents. AIM: Here, we used another well-recognized model organism, the zebrafish (Danio rerio), to explore the behavioral effects of GBR 12909, a highly-affine selective DAT blocker. METHODS: We evaluated zebrafish locomotion, novelty-related exploration, spatial cognition, and social phenotypes in the novel tank, habituation and shoaling tests, following acute 20-min water immersion in GBR 12909. RESULTS: Our findings show hypolocomotion, anxiety-like state, and impaired spatial cognition in fish acutely treated with GBR 12909. This behavioral profile generally parallels that of the DAT knockout rodents and zebrafish, and it overlaps with behavioral effects of other DAT-inhibiting drugs of abuse, such as cocaine and D-amphetamine. CONCLUSION: Collectively, our data support the utility of zebrafish in translational studies on DAT targeting neuropharmacology and strongly implicate DAT aberration as an important mechanisms involved in neurological and psychiatric diseases.

Theoretical simulation and experimental design of selenium and gold incorporated polymer-based microcarriers for ROS-mediated combined photothermal therapy.

Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional "all-in-one" carriers, but also contributes to the development of combined PTT in clinical practice.