Short Chain Chlorinated Paraffins Impaired Spermatogenesis Process in Mice via Inhibiting α-KG/TET Enzyme Activity.

Short chain chlorinated paraffins (SCCPs) are widely found in various environmental media and potentially threaten human health. However, the toxicity mechanisms of SCCPs to the male reproductive system remain unclear. In this study, male BALB/c mice and GC-1 cells were used to investigate the reproductive toxicity of SCCPs and their molecular mechanisms. SCCPs decreased the content of the tricarboxylic acid cycle intermediate α-KG in testicular cells, thus inhibiting the activity of the DNA demethylase TET enzyme and resulting in an increase in the overall methylation level of the testicular genome. Correspondingly, the promoter demethylation and expression of spermatogenesis-related genes Rbm46, Sohlh1, Kit, and Dmrt1 were significantly reduced by SCCPs, which further prevented the transformation of spermatogonia to spermatocytes and reduced sperm quality in mice. The in vitro experiments suggested that the TGFß pathway activated by oxidative stress might be an essential reason for inhibiting the tricarboxylic acid cycle and the reduction of α-KG content in testicular cells induced by SCCPs. Overall, this study reveals a novel metabolic regulatory mechanism of SCCPs-induced spermatogenesis disorders, which provides an essential theoretical basis for the prevention of reproductive toxicity of SCCPs.

Transparent Oil-Water Separating Hydrophobic Sponge Prepared from a Pickering High Internal Phase Emulsion Stabilized by Octadecyltrichlorosilane Grafting Carbon Nanotubes.

Increasingly, oil spills and industrial discharges are wreaking havoc on the water environment; in order to efficiently separate oil and water from sewage containing oil or organic solvents, a novel porous polymer (P(EHA-co-BA)) was prepared by Pickering high internal phase emulsion (HIPE) template method. To obtain polyHIPE with better oil/water separation capacities, octadecyltrichlorosilane (OTS)-modified carbon nanotubes (CNTs) and surfactants were used as costabilizers for HIPE, which improved the stability of HIPE as well as the mechanical properties and the separation efficiency of polyHIPE. In the presence of 1 wt % OTS-CNT adding in the oil phase, 1%OTS-CNT polyHIPE has high porosity (92.21%), favorable hydrophobicity (a water contact angle of 128°), and excellent mechanical properties. As a result, 1%OTS-CNT polyHIPE has high absorption of oils and oily solvents, e.g., dichloromethane up to 36 g/g, and maintains an absorption efficiency of >97% after 20 reapplications. In the formulation of polyHIPE, cinnamaldehyde (CA) has been added to provide superior antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It appears that the novel polyHIPE proposed in this work is a reusable antibacterial porous polymer with promising applications for oil-water separation.

Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID.

COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments.

Assessing the effect of probiotics on tilapia lake virus-infected tilapia: Transmission and immune response.

Probiotics have been used to alleviate disease transmission in aquaculture. However, there are limited studies on probiotic use in modulating tilapia lake virus (TiLV). We assessed commercially available probiotic supplements used in TiLV-infected tilapia and performed mortality and cohabitation assays. We developed a mechanistic approach to predict dose-response interactions of probiotic effects on mortality and immune gene response. We used a susceptible-infected-mortality disease model to assess key epidemiological parameters such as transmission rate and basic reproduction number (R0 ) based on our viral load dynamic data. We found that the most marked benefits of probiotics are significantly associated with immune system enhancements (~30%) and reductions in disease transmission (~80%) and R0 (~70%) in tilapia populations, resulting in a higher tolerance of farming densities (~400 fold) in aquaculture. These findings provide early insights as to how probiotic use-related factors may influence TiLV transmission and the immune responses in TiLV-infected tilapia. Our study facilitates understanding the mode of action of probiotics in disease containment and predicting better probiotic dosages in diet and supplements to achieve the optimal culturing conditions. Overall, our analysis assures that further study of rationally designed and targeted probiotics, or mechanistic modelling is warranted on the basis of promising early data of this approach.

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics.

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches. Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals. Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments. In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

Modelling the effect of vaccination on transmission dynamics of nervous necrosis virus in grouper larvae Epinephelus coioides.

Nervous necrosis virus (NNV) infection in susceptible grouper larvae has been reported to cause high mortalities, leading to great economic losses in aquaculture industry. Although the effects of NNV vaccines on grouper have been broadly investigated, vaccination strategies have not been fully established. To this end, we introduced the parsimonious epidemiological models that explored the assessment of key epidemiological parameters and how they changed when vaccinations showed the effects. We showed that the models capture the published cumulative mortality data accurately. We estimated a basic reproduction number R0  = 2.44 for NNV transmission in grouper larvae without vaccination. To effectively control NNV transmission by vaccination, a model for disease control was also generalized to attain the goals of controlled reproduction number less than 1. Our results indicated that at least 60% of grouper population needed to be immunized for ~75 min. Our data-driven modelling approach that links the transmission dynamics of NNV and vaccination strategies for grouper has the potential to support evidence-based planning and adaptation of integrated control measures. We encourage that the epidemiology-based framework introduced here can be further implemented for establishing effective vaccination and mitigation actions aimed at controlling diseases in fish farming practices.

Quantifying the impact of temperature variation on birnavirus transmission dynamics in hard clams Meretrix lusoria.

Susceptibility of hard clams Meretrix lusoria to birnavirus (BV) infections caused by temperature variations, from a mechanistic perspective, has rarely been explored. We used a deterministic susceptible-infectious-mortality (SIM) model to derive temperature-dependent key epidemiologic parameters based on data sets of viral infections in hard clams subjected to acute temperature changes. To parameterize seasonal pattern dependence, we estimated monthly based cumulative mortality and basic reproduction numbers (R0 ) between 1997 and 2017 by way of statistical analysis. Two alternative disease control models were also proposed to assess status of controlled temperature-mediated BV infection by using, respectively, control reproduction number (RC )-control line criterion and removal strategy-based control measure. We showed that based on RC -control strategy, when temperatures ranged from 15 to 26.8°C, proportion of susceptible hard clams removed should be at least 0.22%. Based on removal-control strategy, we found that by limiting pond water temperature to 25-30°C, together with increased removal rates and periods to remove hard clams, it is better to remove hard clams from June and August to reduce both mortality rate and spread of BV. Our results can be used to monitor BV transmission potential in hard clams that will contribute to government control strategy to eradicate future BV epidemics.

Assessing the population transmission dynamics of tilapia lake virus in farmed tilapia.

A novel virus, tilapia lake virus (TiLV), has been identified as a key pathogen responsible for disease outbreak and mass mortality of farmed tilapia. We used a deterministic susceptible-infectious-mortality (SIM) model to derive key disease information appraised with published TiLV-induced cumulative mortality data. The relationship between tilapia mortality and TiLV exposure dosages was described by the Hill model. Furthermore, a disease control model was proposed to determine the status of controlled TiLV infection using a parsimonious control reproduction number (RC )-control line criterion. Results showed that the key disease determinants of transmission rate and basic reproduction number (R0 ) could be derived. The median R0 estimate was 2.59 in a cohabitation setting with 2.6 × 105  TCID50 fish-1 TiLV. The present RC -control model can be employed to determine whether TiLV containment is feasible in an outbreak farm by quantifying the current level of transmission. The SIM model can then be applied to predict what additional control is required to manage RC  < 1. We offer valuable tools for aquaculture engineers and public health scientists the mechanistic-based assessment that allows a more rigorous evaluation of different control strategies to reduce waterborne diseases in aquaculture farming systems.

Assessing exposure risks for freshwater tilapia species posed by mercury and methylmercury.

Waterborne and dietborne exposures of freshwater fish to mercury (Hg) in the forms of inorganic (Hg(II)) and organic (methylmercury or MeHg) affect their growth, development, and reproduction. However, an integrated mechanistic risk model framework to predict the impact of Hg(II)/MeHg on freshwater fish is lacking. Here, we integrated biokinetic, physiological and biogeographic data to calibrate and then establish key risk indices-hazardous quotient and exceedance risk-for freshwater tilapia species across geographic ranges of several major rivers in Taiwan. We found that Hg(II) burden was highest in kidney followed by gill, intestine, liver, blood, and muscle. Our results showed that Hg was less likely to pose mortality risk (mortality rate less than 5 %) for freshwater tilapia species. However, Hg is likely to pose the potential hazard to aquatic environments constrained by safety levels for aquatic organisms. Sensitivity analysis showed that amount of Hg accumulated in tilapia was most influenced by sediment uptake rate. Our approach opens up new possibilities for predicting future fish population health with the impacts of continued Hg exposure to provide information on which fish are deemed safe for human consumption.

COVID-19 Vaccination Reporting and Adverse Event Analysis in Taiwan.

The COVID-19 pandemic necessitated an urgent global response in vaccine deployment, achieving over 70.6% global vaccination coverage with at least one dose. This study focuses on Taiwan's vaccine administration and adverse event reporting, set against a global backdrop. Using data from Taiwan's Vaccine Adverse Event Reporting System (VAERS) and global vaccination data, this study investigates vaccine safety and the public health implications of vaccination strategies from local and global perspectives. Taiwan's proactive approach, resulting in high vaccination rates, provides a case study for the monitoring and management of vaccine-related adverse events. This study offers insights into the safety profiles of various COVID-19 vaccines and further explores the implications of adverse event reporting rates for vaccine policy and public health strategies. The comparative analysis reveals that, while vaccination has been effective in controlling the virus's spread, safety monitoring remains critical for maintaining public trust. It underscores the necessity of enhanced surveillance and the importance of transparent and tailored risk communication to support informed public health decisions. The findings aim to contribute to the global dialogue on vaccine safety, equitable distribution, evidence-based policy-making, and development of mitigation measures with consideration of local demographics in the ongoing fight against COVID-19.

Burden changes in notifiable infectious diseases in Taiwan during the COVID-19 pandemic.

Background: This study aimed to assess the impact of the COVID-19 pandemic on the disease burden of Taiwan's notifiable infectious diseases (NIDs). We compared disease burdens between the pandemic and pre-pandemic year of 2020 (with non-pharmaceutical interventions (NPIs)) and 2010 (without NPIs), respectively, to understand the overall pandemic impact on NIDs in Taiwan. Methods: Forty-three national NIDs were analyzed using the Statistics of Communicable Diseases and Surveillance Report by estimating the premature death and disability via different transmission categories, sex, and age groups. The study evaluated the impact of diseases by assessing the years lost due to death (YLLs), the duration of living with disability (YLDs), and the overall disability-adjusted life years (DALYs) by measuring both the severity of the illness and its duration. Results: Taiwan recorded 1,577 (2010) and 1,260 (2020) DALYs per million population and lost 43 NIDs, decreasing 317 DALYs per million population. Tuberculosis, HIV/AIDS and acute hepatitis B/D were the leading causes of DALYs, accounting for 89% (2010) and 77% (2020). Conclusion: Overall, this study provided the first insight of changes in disease burdens in NIDs between pre- and post-COVID-19 based on a nationwide viewpoint for further preventive measures and interventions to be focused on specific diseases by associated health administrations and policies.

Measuring disease burden of dominant variants of COVID-19 in Taiwan.

Objectives: The disability-adjusted life years (DALYs) of COVID-19 have been applied as a time-based measurement to estimate years of life lost due to premature mortality or healthy life lost in different countries. Limited information was found for DALYs among different variants of concern (VOC). Methods: Disease severities based on categories of asymptomatic, mild, moderate, severe, and critical cases were explored among different VOC by analyzing the proportions in confirmed cases. DALY or years of healthy life lost due to disability (YLD)-based annual burdens of COVID-19 on different ages, genders as well as trend analysis were also evaluated for VOC in Taiwan. Results: Different trends were observed in years of life lost due to premature mortality (YLLs) or YLD for various age or gender categories. Disease severity at critical stage had the highest percentage for overall YLDs encompassed from 2020 to 2022. Also, critical-grade cases were found to be predominantly caused by Wild-type, Alpha, and Omicron variants in 2020, 2021, and 2022, respectively. Conclusion: Precautionary measures are also suggested for policy makers to take in specific seasons, age or gender groups based on YLL and YLD analyses.

Vasicine attenuates atherosclerosis via lipid regulation, inflammation inhibition, and autophagy activation in ApoE-/- mice.

Atherosclerosis is marked with the accumulation of low-density lipoproteins and chronic inflammation. The anti-inflammatory therapies exert protective effects on atherosclerosis. Vasicine is a bioactive alkaloid with anti-inflammatory activity from a medicinal plant in Ayurveda and Unani. In this study, the effects of vasicine were evaluated on atherosclerosis in vivo and in vitro. The results showed that vasicine alleviated atherosclerotic lesions and regulated the lipid synthesis by reducing the levels of TC, TG, LDL-C and inhibiting the expresses of scavenger receptors (SR-A, CD36 and LOX-1) to inhibit foam cell formations. And vasicine decreased the levels of IL-1ß, IL-6, MCP-1, and TNF-α to modulate inflammatory response. Besides, vasicine downregulated MAPK and PI3K/AKT/mTOR pathway to activated autophagy, which inhibited the procession of atherosclerosis.

Synergistic Antimicrobial Glycyrrhizic Acid-Based Functional Biosensing Composite for Sensitive Glucose Monitoring and Collaborative Wound Healing.

High glucose blood and bacterial infection remain major issues for the slow healing of diabetic wounds, so developing functional biosensing composite with excellent antibacterial and remarkable glucose response sensitivity is necessary and prospective. Herein, by in situ synthesis AgNPs on the surface of self-prepared PTIGA elastomers, PTIGA-AgNPs conductive composites are obtained with efficient synergistic antibacterial effect, excellent mechanical and self-healing properties. The strain of the composites can reach 1800%, and its self-healing efficiency exceeds 90% at 60 °C within 8 h. Both elastomers and composites represent excellent biocompatibility and the antibacterial rate against E. coli and S. aureus exceeded 90%. Moreover, the biosensor assembled from the conductive composites exhibits excellent glucose response sensitivity and stability, with a sensitivity coefficient of 0.518 mA mm-1 in the range of 0.2-3.6 × 10-3 m glucose concentration, as well as a low detection limit of 0.08 × 10-3 m. Furthermore, based on the remarkable antibacterial performance and bioactivity derived from GA, the composites reduce the expression of pro-inflammatory factors and promote the production of anti-inflammatory factors, and effectively promote the regeneration of skin and granulation tissue of wounds in a diabetic full-thickness skin defect model, demonstrating the enormous therapeutic potential in diabetic wound healing.

Disease burden due to COVID-19 in Taiwan: Disability-adjusted life years (DALYs) with implication of Monte Carlo simulations.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has affected a large number of countries. Informing the public and decision makers of the COVID-19's economic burdens is essential for understanding the real pandemic impact. METHODS: COVID-19 premature mortality and disability impact in Taiwan was analyzed using the Taiwan National Infectious Disease Statistics System (TNIDSS) by estimating the sex/age-specific years of life lost through death (YLLs), the number of years lived with disability (YLDs), and the disability-adjusted life years (DALYs) from January 2020 to November 2021. RESULTS: Taiwan recorded 1004.13 DALYs (95% CI: 1002.75-1005.61) per 100,000 population for COVID-19, with YLLs accounting for 99.5% (95% CI: 99.3%99.6%) of all DALYs, with males suffering more from the disease than females. For population aged ≥ 70 years, the disease burdens of YLDs and YLLs were 0.1% and 99.9%, respectively. Furthermore, we found that duration of disease in critical state contributed 63.9% of the variance in DALY estimations. CONCLUSIONS: The nationwide estimation of DALYs in Taiwan provides insights into the demographic distributions and key epidemiological parameter for DALYs. The essentiality of enforcing protective precautions when needed is also implicated. The higher YLLs percentage in DALYs also revealed the fact of high confirmed death rates in Taiwan. To reduce infection risks and disease, it is crucial to maintain moderate social distancing, border control, hygiene measures, and increase vaccine coverage levels.

Control measure implications of COVID-19 infection in healthcare facilities reconsidered from human physiological and engineering aspects.

The Wells-Riley model invokes human physiological and engineering parameters to successfully treat airborne transmission of infectious diseases. Applications of this model would have high potentiality on evaluating policy actions and interventions intended to improve public safety efforts on preventing the spread of COVID-19 in an enclosed space. Here, we constructed the interaction relationships among basic reproduction number (R0) - exposure time - indoor population number by using the Wells-Riley model to provide a robust means to assist in planning containment efforts. We quantified SARS-CoV-2 changes in a case study of two Wuhan (Fangcang and Renmin) hospitals. We conducted similar approach to develop control measures in various hospital functional units by taking all accountable factors. We showed that inhalation rates of individuals proved crucial for influencing the transmissibility of SARS-CoV-2, followed by air supply rate and exposure time. We suggest a minimum air change per hour (ACH) of 7 h-1 would be at least appropriate with current room volume requirements in healthcare buildings when indoor population number is < 10 and exposure time is < 1 h with one infector and low activity levels being considered. However, higher ACH (> 16 h-1) with optimal arranged-exposure time/people and high-efficiency air filters would be suggested if more infectors or higher activity levels are presented. Our models lay out a practical metric for evaluating the efficacy of control measures on COVID-19 infection in built environments. Our case studies further indicate that the Wells-Riley model provides a predictive and mechanistic basis for empirical COVID-19 impact reduction planning and gives a framework to treat highly transmissible but mechanically heterogeneous airborne SARS-CoV-2.

Revealing the Impact of Micro-SiO2 Filer Content on the Anti-Corrosion Performance of Water-Borne Epoxy Resin.

Due to green development in recent years, water-borne epoxy resins (WBE) have become increasingly popular since they generate the lowest level of volatile organic compounds (VOC) during curing. However, because of the large surface tension of water, it is easy to produce voids and cracks during the curing process of the coating. An electrochemical strategy was used in this study to assess the impact of different SiO2 content on the corrosion performance of a WBE coating, in which micron spherical SiO2 particles were synthesized in a liquid phase reduction. The results showed that the synthesized micron spherical SiO2 particles were about 800 ± 50 nm in diameter and in an amorphous state. By hydrophilizing the surfaces of these SiO2 particles, uniform dispersion in an aqueous solvent and a WBE can be achieved. It is important to note that adding a small or excessive amount of SiO2 to a coating will not improve corrosion resistance and may even reduce corrosion resistance. With the appropriate modification of SiO2, corrosion resistance of composite coatings is greatly enhanced, as is the adhesion between the coatings and the metallic substrates. Because the appropriately modified SiO2 can effectively fill the pores that are formed during the curing process, a corrosive medium is less likely to react with the matrix when the medium comes into contact with the matrix. Based on their incorporation content of 3 wt.%, their corrosion resistance is the best after 16 cycles of AC-DC-AC accelerated corrosion tests.

Demographic Control Measure Implications of Tuberculosis Infection for Migrant Workers across Taiwan Regions.

A sharp increase in migrant workers has raised concerns for TB epidemics, yet optimal TB control strategies remain unclear in Taiwan regions. This study assessed intervention efforts on reducing tuberculosis (TB) infection among migrant workers. We performed large-scale data analyses and used them to develop a control-based migrant worker-associated susceptible-latently infected-infectious-recovered (SLTR) model. We used the SLTR model to assess potential intervention strategies such as social distancing, early screening, and directly observed treatment, short-course (DOTS) for TB transmission among migrant workers and locals in three major hotspot cities from 2018 to 2023. We showed that social distancing was the best single strategy, while the best dual measure was social distancing coupled with early screening. However, the effectiveness of the triple strategy was marginally (1-3%) better than that of the dual measure. Our study provides a mechanistic framework to facilitate understanding of TB transmission dynamics between locals and migrant workers and to recommend better prevention strategies in anticipation of achieving WHO's milestones by the next decade. Our work has implications for migrant worker-associated TB infection prevention on a global scale and provides a knowledge base for exploring how outcomes can be best implemented by alternative control measure approaches.

Estimates of lung burden risk associated with long-term exposure to TiO2 nanoparticles as a UV-filter in sprays.

Titanium dioxide (TiO2) nanoparticles (NPs) are employed as an ultraviolet filter in sunscreen products because of their high ultraviolet absorptivity. However, sunscreen sprays may pose health risks due to the toxicity of inhaled TiO2 NPs. Therefore, we estimated the potential human health risk posed by inhaled TiO2 NPs emitted from sunscreen sprays. The physiology-based lung model was employed to predict the lung TiO2 NPs burden caused by long-term exposure. A Hill-based dose-response model described the relationship between lung inflammation and TiO2 NP accumulation. The Weibull threshold model was used to estimate the threshold amount of accumulation inducing 0.5% of the maximum increase in neutrophils. The potential health risk was assessed using a hazard quotient-based probabilistic risk model. All data obtained to date indicate that application of sunscreen sprays poses no significant health risk. However, using data simulations based on the threshold criterion, we discovered that in terms of practical strategies for preventing the risks posed by inhaled TiO2 NPs emitted from spray products, the suggested daily use amount and pressing number are 40 g (95% confidence interval: 11-146 g) and 66 (18-245), respectively. In this study, we successfully translated the potential health risk of long-term exposure to NP-containing sunscreen sprays and recommendations for daily application into mechanistic insights.

Toxicokinetic/toxicodynamic-based risk assessment of freshwater fish health posed by microplastics at environmentally relevant concentrations.

The pervasive contamination of microplastics (MPs) in freshwater ecosystems is of emerging concern. Mechanistic link between exposure and effect on assessing health risk of freshwater fish posed by environmental MPs, however, is more limited. Our study filled this gap by developing a toxicokinetic/toxicodynamic (TK/TD)-based risk assessment framework to examine health effects of zebrafish and red tilapia responses to environmental concentrations of MPs appraised with a variety of valuable published data on a global scale. We assessed organ-specific TK parameters and mean residence times for polystyrene (PS)-MPs-exposed freshwater fish in size- and concentration-dependent manners. We estimated the relatively sensitive benchmark concentrations (BMCs) of PS-MPs for oxidative stress in zebrafish and detoxification in red tilapia to be ~1.0 and ~119 µg g-1, respectively. Based on continental scale MPs trends, the high MPs concentrations were over Asia, with a mean value of 36 mg L-1. Given metabolic disturbances in zebrafish and red tilapia as bioindicators, we found that MPs pollution was highly likely to enhance fish health risks and that this factor must therefore be considered in evaluations of MPs susceptibility of freshwater fish. Our TK/TD-based risk scheme could help inform intensified efforts to mitigate environmental MPs pollution in order to benefit freshwater fish species and people who depend on healthy stocks of different fish.