Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study.

INTRODUCTION: We hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: We conducted an efficacy-implementation pilot study of MPE for T2D and CKD for primary care provider (PCP)-patient dyads at an academic health system. MPE included (1) a dashboard to identify patients without a prescription for sodium-glucose cotransporter-2 inhibitors (SGLT2i) and without a maximum dose prescription for renin-angiotensin-aldosterone system inhibitors (RAASi), (2) a multidisciplinary team of specialists to provide recommendations using e-consult templates, and (3) a workflow to deliver timely e-consult recommendations to PCPs. In-depth interviews were conducted with PCPs and specialists to assess feasibility, acceptability, and appropriateness of MPE and were analyzed using an iterative qualitative analysis approach to identify major themes. Prescription data were extracted from the electronic health record to assess preliminary effectiveness to increase GDMT. RESULTS: 20 PCPs agreed to participate, 18 PCPs received MPEs for one of their patients with T2D and CKD, and 16 PCPs and 2 specialists were interviewed. Major themes were as follows: appropriateness of prioritization of GDMT for T2D and CKD, acceptability of the content of the recommendations, PCP characteristics impact experience with MPE, acceptability and appropriateness of multidisciplinary collaboration, feasibility of MPE to overcome patient-specific barriers to GDMT, and appropriateness of workflow. At 6 months postbaseline, 7/18 (39%) patients were newly prescribed an SGLT2i, and 7/18 (39%) patients were either newly prescribed or had increased dose of RAASi. CONCLUSIONS: MPE was an acceptable and appropriate health system strategy to identify and address gaps in GDMT among patients with T2D and CKD. Adopting MPE could enhance GDMT, though PCPs raised feasibility concerns which could be improved with program enhancements, including follow-up e-consults for reinforcement, and administrative support for navigating system-level barriers.

Strategies for regulating the intensity of different cyanobacterial blooms: Insights from the dynamics and stability of bacterioplankton communities.

The occurrence of cyanobacterial blooms is increasing in frequency and magnitude due to climate change and human activities, which poses a direct threat to drinking water security. The impacts of abiotic and biotic factors on the development of blooms have been well studied; however, control strategies for different bloom intensities have rarely been explored from the perspective of the dynamics and stability of bacterioplankton communities. Here, a network analysis was used to investigate the interactions and stability of microbial communities during different periods of R. raciborskii bloom in an inland freshwater lake. The abundance and diversity of rare taxa were significantly higher than that of abundant taxa throughout the bloom cycle. At the pre-bloom (PB) stage, microbial interactions among the different bacterial groups were weak but strongly negatively correlated, indicating low robustness and weak disturbance resistance within the community. However, community stability was better, and microbial interactions became more complicated at the high-bloom (HB) and low-bloom (LB) stages. Interestingly, rare taxa were significantly responsible for community stability and connectivity despite their low relative abundance. The Mantel test revealed that Secchi depth (SD), orthophosphate (PO43--P), and dissolved oxygen (DO) were significantly positively correlated with abundant taxa, rare taxa and PB. DO was significantly positively correlated with HB, intermediate taxa, and rare taxa, while water temperature (WT), N/P and total nitrogen (TN) were significantly positively correlated with LB, abundant taxa, intermediate taxa, and rare taxa. These findings suggest that reducing the PO43--P concentration at the PB stage may be an effective approach to preventing the development of R. raciborskii blooms, while regulating rare taxa at the HB and LB stages may be a key factor in controlling R. raciborskii blooms.

Formulating Local Environment of Oxygen Mitigates Voltage Hysteresis in Li-Rich Materials.

Li-rich cathode materials have emerged as one of the most prospective options for Li-ion batteries owing to their remarkable energy density (>900 Wh kg-1). However, voltage hysteresis during charge and discharge process lowers the energy conversion efficiency, which hinders their application in practical devices. Herein, the fundamental reason for voltage hysteresis through investigating the O redox behavior under different (de)lithiation states is unveiled and it is successfully addressed by formulating the local environment of O2-. In Li-rich Mn-based materials, it is confirmed that there exists reaction activity of oxygen ions at low discharge voltage (<3.6 V) in the presence of TM-TM-Li ordered arrangement, generating massive amount of voltage hysteresis and resulting in a decreased energy efficiency (80.95%). Moreover, in the case where Li 2b sites are numerously occupied by TM ions, the local environment of O2- evolves, the reactivity of oxygen ions at low voltage is significantly inhibited, thus giving rise to the large energy conversion efficiency (89.07%). This study reveals the structure-activity relationship between the local environment around O2- and voltage hysteresis, which provides guidance in designing next-generation high-performance cathode materials.

Material Hardship Predicts Response Bias in Loss-Averse Decisions: The Roles of Anxiety and Cognitive Control.

Income poverty is associated with an enhanced tendency to avoid losses in economic decisions, which can be driven by a response bias (risk avoidance) and a valuation bias (loss aversion). However, the impact of non-income dimensions of poverty on these biases remains unclear. The current study tested the impact of material hardship on these biases, and the mediating effects of anxiety, depression, and cognitive control in these associations. Healthy adults (N = 188) completed questionnaire and behavioral measures of the variables. Results of regression-based analyses showed that participants who reported higher material hardship exhibited greater response bias, but not valuation bias. This effect was mediated by anxiety. Although material hardship predicted lower cognitive control, cognitive control did not mediate the association between material hardship and either type of bias. These findings suggest that material hardship may lead to economic decision-making biases because it impacts emotional states rather than cognitive control.

Oxygen Vacancies Driven by Co in the Deeply Charged State Inducing Intragranular Cracking of Ni-Rich Cathodes.

Intragranular cracking within the material structure of Ni-rich (LiNix Coy Mn1 - x - y , x ≥0.9) cathodes greatly threatens cathode integrity and causes capacity degradation, yet its atomic-scale incubation mechanism is not completely elucidated. Notably, the physicochemical properties of component elements fundamentally determine the material structure of cathodes. Herein, a diffusion-controlled incubation mechanism of intragranular cracking is unraveled, and an underlying correlation model with Co element is established. Multi-dimensional analysis reveals that oxygen vacancies appear due to the charge compensation from highly oxidizing Co ions in the deeply charged state, driving the transition metal migration to Li layer and layered to rock-salt phase transition. The local accumulation of two accompanying tensile strains collaborates to promote the nucleation and growth of intragranular cracks along the fragile rock-salt phase domain on (003) plane. This study focuses on the potential risks posed by Co to the architectural and thermal stability of Ni-rich cathodes and is dedicated to the compositional design and performance optimization of Ni-rich cathodes.

Molecular mechanism and therapeutic significance of essential amino acids in metabolically associated fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), also known as metabolically associated fatty liver disease (MAFLD), is a systemic metabolic disease characterized by lipid accumulation in the liver, lipid toxicity, insulin resistance, intestinal dysbiosis, and inflammation that can progress from simple steatosis to nonalcoholic steatohepatitis (NASH) and even cirrhosis or cancer. It is the most prevalent illness threatening world health. Currently, there are almost no approved drug interventions for MAFLD, mainly dietary changes and exercise to control weight and regulate metabolic disorders. Meanwhile, the metabolic pathway involved in amino acid metabolism also influences the onset and development of MAFLD in the body, and most amino acid metabolism takes place in the liver. Essential amino acids are those amino acids that must be supplemented from outside the diet and that cannot be synthesized in the body or cannot be synthesized at a rate sufficient to meet the body's needs, including leucine, isoleucine, valine (collectively known as branched-chain amino acids), tryptophan, phenylalanine (which are aromatic amino acids), histidine, methionine, threonine and lysine. The metabolic balance of the body is closely linked to these essential amino acids, and essential amino acids are closely linked to the pathophysiological process of MAFLD. In this paper, we will focus on the metabolism of essential amino acids in the body and further explore the therapeutic strategies for MAFLD based on the studies conducted in recent years.

Trajectories of Opioid Misuse and Opioid Use Disorder Among Adults With Chronic Pain and HIV: An Observational Study.

OBJECTIVES: In a longitudinal cohort of patients with HIV and chronic pain, we sought to (1) identify trajectories of opioid misuse and opioid use disorder (OUD) symptoms, and to (2) determine whether prescription opioid dose was associated with symptom trajectories. METHODS: We leveraged an existing 12-month longitudinal observational study, Project PIMENTO, of persons living with HIV and chronic pain who received care at a hospital system in the Bronx, New York. A quota sampling strategy was used to ensure variability of prescribed opioid use in the recruited sample. Research interviews occurred quarterly and assessed opioid behaviors and criteria for OUD. To describe symptom trajectories, we conducted 2 separate longitudinal latent class analyses to group participants into (1) opioid misuse and (2) OUD trajectories. Finally, we used multinomial logistic regression models to examine the relationship between baseline prescription opioid dose and symptom trajectories. RESULTS: Of 148 total participants, at baseline 63 (42.6%) had an active opioid prescription, 69 (46.6%) met the criteria for current opioid misuse, and 44 (29.7%) met the criteria for current OUD. We found 3 opioid misuse and 3 OUD symptom trajectories, none of which showed worsened symptoms over time. In addition, we found that higher prescription opioid dose at baseline was associated with a greater OUD symptom trajectory. CONCLUSIONS: Opioid misuse and OUD were common but stable or decreasing over time. Although these results are reassuring, our findings also support prior studies that high-dose opioid therapy is associated with greater OUD symptoms.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.

miR-2765 involved in ammonia nitrogen stress via negative regulation of autophagy in shrimp.

MicroRNA (miRNA) is a highly conserved non-coding tiny endogenous RNA molecule that regulates various cellular functions by inhibiting mRNA translation or promoting the degradation of proteins. In this study, we identified a specific miRNA (designed as Pva-miR-2765) from Penaeus vannamei, which widely distributed in different tissues of shrimp, with the highest concentration found in the intestine. Through fluorescence in situ hybridization (FISH), we observed that Pva-miR-2765 is primarily located in the cytoplasm. Interestingly, we found that the expression of Pva-miR-2765 significantly decreased in hemocytes, hepatopancreas and gill under ammonia nitrogen stress. Furthermore, when Pva-miR-2765 was silenced, the autophagy level in shrimp significantly increased. Additionally, Pva-miR-2765 was found to promote pathological damage in the hepatopancreas of shrimp. Subsequently, correlation analysis revealed a negative relationship between the expression of Pva-miR-2765 and PvTBC1D7. To confirm this interaction, we conducted a dual luciferase reporter gene assay, which demonstrated that Pva-miR-2765 inhibit the expression of PvTBC1D7 by interacting with its 3'UTR. And the expression level of PvTBC1D7 in shrimp decreased significantly under ammonia nitrogen stress in Pva-miR-2765 overexpressed. Our findings suggest that Pva-miR-2765 can reduce autophagy in P. vannamei by inhibiting the regulation of PvTBC1D7, thereby participating in the oxidative stress of shrimp caused by ammonia nitrogen stress.

Parental Psychological Control, the Parent-Adolescent Relationship, and Non-suicidal Self-Injury Among Chinese Adolescents: The Moderating Effect of the Oxytocin Receptor Gene rs53576 Polymorphism.

Parental psychological control (PPC) is associated with adolescent non-suicidal self-injury (NSSI); however, its underlying mechanisms have not been extensively investigated. Considering that genetic and environmental factors interactively influence adolescent development, this study examined whether the parent-adolescent relationship mediated the link between PPC and adolescent NSSI, and whether this mediating process was moderated by the oxytocin receptor gene rs53576 polymorphism (OXTR rs53576). Participants comprised 673 adolescents (Meanage = 12.81 years, SD = 0.48 years) who completed questionnaires regarding PPC, the parent-adolescent relationship, and NSSI. DNA was extracted from each participant's saliva samples. The results indicated that the positive association between PPC and adolescent NSSI was mediated by the parent-adolescent relationship. Moreover, this indirect link was stronger for adolescents with AA homozygotes of OXTR rs53576 than for those with the GG or AG genotype. These findings extend our understanding of the association between PPC and adolescent NSSI and suggest that a simultaneous focus on PPC, the parent-adolescent relationship, and OXTR rs53576 may favor NSSI interventions.

Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study.

We conducted a retrospective cohort study to assess whether treatment with nirmatrelvir/ritonavir was associated with a reduced risk of long COVID. We enrolled 500 adults with confirmed SARS-CoV-2 who were eligible for nirmatrelvir/ritonavir; 250 who took nirmatrelvir/ritonavir and 250 who did not. The primary outcome was the development of one or more of eleven prespecified long COVID symptoms, assessed through a structured telephone interview four months after the positive SARS-CoV-2 test. Multivariable logistic regression models controlled for age, sex, race/ethnicity, chronic conditions, and COVID-19 vaccination status. We found that participants who took nirmatrelvir/ritonavir were no less likely to develop long COVID symptoms, compared to those who did not take the medication (44% vs. 49.6%, p = 0.21). Taking nirmatrelvir/ritonavir was associated with a lower odds of two of the eleven long COVID symptoms, brain fog (OR 0.58, 95% CI 0.38-0.88) and chest pain/tightness (OR 0.51, 95% CI 0.28-0.91). Our finding that treatment with nirmatrelvir/ritonavir was not associated with a lower risk of developing long COVID is different from prior studies that obtained data only from electronic medical records.

Correction: Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states.

Correction for 'Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states' by Sujiao Cao et al., Chem. Soc. Rev., 2023, https://doi.org/10.1039/d3cs00087g.

Reactive oxygen nanobiocatalysts: activity-mechanism disclosures, catalytic center evolutions, and changing states.

Benefiting from low costs, structural diversities, tunable catalytic activities, feasible modifications, and high stability compared to the natural enzymes, reactive oxygen nanobiocatalysts (RONBCs) have become dominant materials in catalyzing and mediating reactive oxygen species (ROS) for diverse biomedical and biological applications. Decoding the catalytic mechanism and structure-reactivity relationship of RONBCs is critical to guide their future developments. Here, this timely review comprehensively summarizes the recent breakthroughs and future trends in creating and decoding RONBCs. First, the fundamental classification, activity, detection method, and reaction mechanism for biocatalytic ROS generation and elimination have been systematically disclosed. Then, the merits, modulation strategies, structure evolutions, and state-of-art characterisation techniques for designing RONBCs have been briefly outlined. Thereafter, we thoroughly discuss different RONBCs based on the reported major material species, including metal compounds, carbon nanostructures, and organic networks. In particular, we offer particular insights into the coordination microenvironments, bond interactions, reaction pathways, and performance comparisons to disclose the structure-reactivity relationships and mechanisms. In the end, the future challenge and perspectives for RONBCs are also carefully summarised. We envision that this review will provide a comprehensive understanding and guidance for designing ROS-catalytic materials and stimulate the wide utilisation of RONBCs in diverse biomedical and biological applications.

Integrated analysis of a miRNA-mRNA network related to immunity and autophagy in Macrobrachium rosenbergii infected with Aeromonas hydrophila.

MicroRNAs (miRNAs) are a group of RNAs that regulate gene expression in the post-transcriptionally. miRNAs can regulate numerous processes, such as the immune response, due to their dynamic expression patterns. The giant freshwater prawn Macrobrachium rosenbergii is a major freshwater aquaculture prawn that is attacked by various bacteria, including Aeromonas hydrophila. For this study, we performed an analysis of the miRNA and mRNA transcriptome analysis of M. rosenbergii which was infected with A. hydrophila. We identified 56 differentially expressed miRNAs (DEMs) and 1542 differentially expressed mRNAs. Furthermore, an integrated analysis of miRNA-mRNA expression led to the identification of 729 differentially predicted target genes (DETGs) of the DEMs. Multiple functional categories related to immunity, apoptosis, and autophagy were found to be enriched in the DETGs. During the infection of M. rosenbergii by A. hydrophila, an elaborate regulatory network involving Toll and immune deficiency (IMD) signaling, mitogen-activated protein kinase (MAPK) signaling, lysosome, and cell apoptosis was formed by a complex interplay of 40 crucial DEMs and 22 DETGs, all associated with the immune and autophagy pathway. The findings suggest that infection with A. hydrophila triggers intricate responses in both miRNA and mRNA, significantly impacting immune and autophagy processes in M. rosenbergii.

Colonial morphology weakens the response of different inorganic carbon uptake systems to CO2 levels in Microcystis population.

Rising atmospheric CO2 concentration negatively impacts aquatic ecosystems and may induce evolutionary changes in the CO2-concentrating mechanism (CCM) of cyanobacteria. As the most notorious freshwater cyanobacteria, Microcystis strains have high phenotypic plasticity to form colonies and blooms in lakes and reservoirs worldwide. However, phenotypic plasticity of Microcystis responses to elevated CO2 is still a major open question. Here, we studied how Microcystis strains with two genotype of inorganic carbon uptake systems, bicA and sbtA, and different colonial morphology response to 200 ppm, 400 ppm, and 800 ppm CO2 levels. The results revealed that sbtA genotypes showed significantly higher specific growth rates, Chl a concentration, and photosynthetic efficiency at 200 ppm CO2, whereas higher specific growth rates, Chl a concentration, and photosynthetic efficiency were found in bicA genotype at 800 ppm CO2. The highest values of specific growth rates, Chl a concentration, Fv/Fm, and maximal net photosynthesis (Pm) were observed in unicellular morphology, followed by small colony and large colonial morphology at all CO2 levels. The values of K0.5 (DIC), K0.5 (CO2), and K0.5 (HCO3-) in the large colonials increased with rising CO2 levels, but these values significantly decreased in the unicellular and small colonials. ANOSIM analysis indicated that colonial morphology reduced significantly inter-group differences between bicA and sbtA genotypes at all CO2 treatments. These results suggest that colonial morphology of Microcystis can weakens the response of different inorganic carbon uptake systems to CO2 levels. Moreover, phenotypic and genotypic plasticity is likely to broaden strongly the fitness of Microcystis from rising atmospheric CO2.

Growth-coupled high throughput selection for directed enzyme evolution.

Directed enzyme evolution has revolutionized the rapid development of enzymes with desired properties. However, the lack of a high-throughput method to identify the most suitable variants from a large pool of genetic diversity poses a major bottleneck. To overcome this challenge, growth-coupled in vivo high-throughput selection approaches (GCHTS) have emerged as a novel selection system for enzyme evolution. GCHTS links the survival of the host cell with the properties of the target protein, resulting in a screening system that is easily measurable and has a high throughput-scale limited only by transformation efficiency. This allows for the rapid identification of desired variants from a pool of >109 variants in each experiment. In recent years, GCHTS approaches have been extensively utilized in the directed evolution of multiple enzymes, demonstrating success in catalyzing non-native substrates, enhancing catalytic activity, and acquiring novel functions. This review introduces three main strategies employed to achieve GCHTS: the elimination of toxic compounds via desired variants, enabling host cells to thrive in hazardous conditions; the complementation of an auxotroph with desired variants, where essential genes for cell growth have been eliminated; and the control of the transcription or expression of a reporter gene related to host cell growth, regulated by the desired variants. Additionally, we highlighted the recent developments in the in vivo continuous evolution of enzyme technology, including phage-assisted continuous evolution (PACE) and orthogonal DNA Replication (OrthoRep). Furthermore, this review discusses the challenges and future prospects in the field of growth-coupled selection for protein engineering.

School climate and adolescents' prosocial behavior: the mediating role of perceived social support and resilience.

Prosocial behavior is crucial for adolescent socialization and plays a positive role in all aspects of adolescent development. Based on ecosystem theory and self-determination theory, this study aimed to explore the relationship among school climate, perceived social support, psychological resilience, and prosocial behavior. With 1,688 high school students being sampled, we utilized the Perceived School Climate Questionnaire, the Perceived Social Support Scale, the Chinese Version of Mental Resilience Scale, and the Adolescent Prosocial Tendency Scale. The results showed that: (1) school climate, perceived social support, psychological resilience, and prosocial behavior were all positively correlated; (2) perceived social support and psychological resilience could independently mediate the relationship between school climate and prosocial behavior; these two mediating variables could develop a chain mediation effect to influence the link between school climate and prosocial behavior.

Amorphization-Modulated Metal Sulfides with Boosted Active Sites and Kinetics for Efficient Enzymatic Colorimetric Biodetection.

Colorimetric biosensing has become a popular sensing method for the portable detection of a variety of biomarkers. Artificial biocatalysts can replace traditional natural enzymes in the fields of enzymatic colorimetric biodetection; however, the exploration of new biocatalysts with efficient, stable, and specific biosensing reactions has remained challenging so far. Here, to enhance the active sites and overcome the sluggish kinetics of metal sulfides, the creation of an amorphous RuS2 (a-RuS2 ) biocatalytic system is reported, which can dramatically boost the peroxidase-mimetic activity of RuS2 for the enzymatic detection of diverse biomolecules. Due to the existence of abundant accessible active sites and mildly surface oxidation, the a-RuS2 biocatalyst displays a twofold Vmax value and much higher reaction kinetics/turnover number (1.63 × 10-2 s-1 ) compared to that of the crystallized RuS2 . Noticeably, the a-RuS2 -based biosensor shows an extremely low detection limit of H2 O2 (3.25 × 10-6 m), l-cysteine (3.39 × 10-6 m), and glucose (9.84 × 10-6 m), respectively, thus showing superior detection sensitivity to many currently reported peroxidase-mimetic nanomaterials. This work offers a new path to create highly sensitive and specific colorimetric biosensors in detecting biomolecules and also provides valuable insights for engineering robust enzyme-like biocatalysts via amorphization-modulated design.

Intracellular behavior of Nocardia seriolae and its apoptotic effect on RAW264.7 macrophages.

Nocardia seriolae, an intracellular gram-positive pathogen, is prone to infecting immunocompromised and surface-damaged fish, causing serious losses to the aquaculture industry. Although a previous study has demonstrated that N. seriolae infects macrophages, the persistence of this bacterium in macrophages has not been well characterized. To address this gap, we used the macrophage cell line RAW264.7, to investigate the interactions between N. seriolae and macrophages and deciphered the intracellular survival mechanism of N. seriolae. Confocal and light microscopy revealed that N. seriolae entered macrophages 2 hours post-inoculation (hpi), were phagocytosed by macrophages at 4-8 hpi, and induced the formation of multinucleated macrophages by severe fusion at 12 hpi. Flow cytometry, evaluation of mitochondrial membrane potential, release of lactate dehydrogenase, and observation of the ultrastructure of macrophages revealed that apoptosis was induced in the early infection stage and inhibited in the middle and later periods of infection. Additionally, the expression of Bcl-2, Bax, Cyto-C, Caspase-3, Capase-8, and Caspase-9 was induced at 4 hpi, and then decreased at 6-8 hpi, illustrating that N. seriolae infection induces the activation of extrinsic and intrinsic apoptotic pathways in macrophages, followed by the inhibition of apoptosis to survive inside the cells. Furthermore, N. seriolae inhibits the production of reactive oxygen species and releases large amounts of nitric oxide, which persists in macrophages during infection. The present study provides the first comprehensive insight into the intracellular behavior of N. seriolae and its apoptotic effect on macrophages and may be important for understanding the pathogenicity of fish nocardiosis.