HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Scaling laws for lattice distortions: Application to high entropy alloys.

Lattice distortions are intrinsic features of all solid solution alloys associated with varying atomic radii; this phenomenon facilitates the formation of single-phase solid solutions. Using high-entropy alloys (HEAs), as an example, we investigate the influence of variations in inter-atomic separations for stabilizing and controlling their structural, mechanical, and thermodynamic properties. This is done through a combination of statistical mechanics analysis and molecular dynamics simulations on simplified 2D systems, as well as a 3D crystals with harmonic and anharmonic inter-atomic bonds with varying natural inter-atomic separations. We demonstrate that the impact of this inter-atomic length disorder (representing static lattice distortion) and temperature fluctuations (representing dynamic lattice distortion) on fundamental and universal thermodynamic, structural, and elastic characteristics are similar and can be unified through effective temperature; i.e. a scaling law for HEAs that establishes a relationship between these factors. This scaling law reveals that different HEAs (i.e. varying degrees of local lattice distortions) collapse onto a single curve when plotted against the effective temperature. We demonstrate that lattice distortion significantly enhances the stability of solid solution alloys (relative to phase separation or ordering by effectively increasing the temperature of the system; this stabilization effect is particularly pronounced in HEAs).

Unveiling the hidden effects of hypoxia: Pituitary damage and hormonal imbalance in fat greenling (Hexagrammos otakii).

BACKGROUND: In fisheries, hypoxia stress is one of the most common environmental stresses that often lead to the death of large numbers of fish and cause significant economic losses. The pituitary, an important endocrine gland, lies below the hypothalamus region of the brain. It plays a crucial part in controlling vital physiological functions in fish, such as growth, reproduction, and responses to stress. However, the detailed mechanisms of how hypoxia affects these physiological processes via the pituitary remain largely unknown. METHODS: Fat greenlings (Hexagrammous otakii) were exposed to different dissolved oxygen (DO = 7. 6 mg/L and DO = 2 mg/L) for 24 h. miRNA-mRNA association analysis of H. otakii pituitary after hypoxia stress. Detecting apoptosis in H. otakii pituitary using Tunel and qPCR. Subsequent detection of hormones in H. otakii liver, gonads and serum by ELISA. RESULTS: In this study, hypoxia causes immune system disorders and inflammatory responses through the combined analysis of miRNAs and mRNAs. Subsequent verification indicated a significant accumulation of reactive oxygen species (ROS) subsequent to hypoxia treatment. The overproduction of ROS cause oxidative stress and apoptosis in the pituitary, ultimately causing pituitary damage and reduced growth hormone and luteinising hormone release. CONCLUSIONS: According to the association study of miRNA-mRNA, apoptosis problems caused by hypoxia stress result in H. otakii pituitary damage. In the meantime, this work clarifies the possible impact of hypoxia-stress on the pituitary cells, as well as on the gonadal development and growth of H. otakii.

NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis.

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

Complex-Amplitude Programmable Versatile Metasurface Platform Driven by Guided Wave.

Metasurfaces have shown unparalleled controllability of electromagnetic (EM) waves. However, most of the metasurfaces need external spatial feeding sources, which renders practical implementation quite challenging. Here, a low-profile programmable metasurface with 0.05λ0 thickness driven by guided waves is proposed to achieve dynamic control of both amplitude and phase simultaneously. The metasurface is fed by a guided wave traveling in a substrate-integrated waveguide, avoiding external spatial sources and complex power divider networks. By manipulating the state of the p-i-n diodes embedded in each meta-atom, the proposed metasurface enables 1-bit amplitude switching between radiating and nonradiating states, as well as a 1-bit phase switching between 0° and 180°. As a proof of concept, two advanced functionalities, namely, low sidelobe-level beam scanning and Airy beam generation, are experimentally demonstrated with a single platform operating in the far- and near-field respectively. Such complex-amplitude, programmable, and low-profile metasurfaces can overcome integration limitations of traditional metasurfaces, and open up new avenues for more accurate and advanced EM wave control within an unprecedented degree of freedom.

Analysis of the inhibitory effect of a refined human resources salary system on job transfer and transfer tendency of nurses.

To evaluate the impact of a refined human resources salary system on job transfer and transfer tendency. From January 2019 to December 2019, a refined human resources salary system reform was implemented at the Tangshan Workers' Hospital in Hebei Province, and the job transfer and transfer tendency of clinical nurses was assessed using the nurse job transfer tendency scale before and 1 year after the intervention. A total of 640 nurses completed the intervention and evaluation. The results showed that the job transfer rate following the intervention reduced to 0.22%. The total score of clinical nurse job transfer tendency was (10.80 ±â€…3.23) before the intervention and (9.66 ±â€…3.58) after 1 year of intervention, which was substantially lower (P < .001). The satisfaction scores of nurses on performance-based salary increased significantly from (67.83 ±â€…18.54) before the intervention to (80.66 ±â€…15.87) after intervention, with varying degrees of increase observed in each dimension (P < .001). The refined human resources salary system effectively reduced job transfer and transfer tendency of clinical nurses in hospital nursing management, and can be widely promoted and applied.

The Effects of Processing Parameters during the Wire Arc Additive Manufacturing of 308L Stainless Steel on the Formation of a Thin-Walled Structure.

Wire arc additive manufacturing (WAAM) excels in producing medium to large components with a high deposition rate. Process optimization is crucial for uniform, defect-free components. This research employs orthogonal experimental design and response surface methodology (RSM) to control TIG WAAM-ed 308L stainless steel components. Varied parameters, including tungsten electrode angle, welding current, and speed, target weld bead attributes. Analysis of variance (ANOVA) evaluates multi-processing parameter influence on weld bead formation. Comparison with experimental results confirms accurate modeling of the relationship between parameters and bead attributes. The study optimizes process parameters and swing to enhance dimensional accuracy in single-layer and multi-layer components, improving precision, quality, and accuracy in thin-walled structures.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

[Ecosystem CO2 Exchange and Its Environmental Regulation of a Restored Wetland in the Liaohe River Estuary].

Coastal wetlands are important carbon sinks， and they contribute to reducing the effects of global warming. This study used the eddy covariance method to detect the CO2 flux in the restoration wetland of the Liaohe River estuary in 2021 and investigate the characteristics of ecosystem CO2 exchange and its environmental control factors. The aim was to assess the carbon source/sink capacity of salt marshes in the restored area and to provide data support and theoretical basis for evaluating the effectiveness of ecological restoration projects. The study revealed "U" curves in spring and autumn， "V" curves in summer， and horizontal lines in winter for the average daily variation curve of net ecosystem CO2 exchange （NEE） in the restored area. Its carbon sink efficiencies were -40.06， -63.62， 2.33， and 34.43 g·m-2 in the spring， summer， autumn， and winter， respectively. In the restored area， the daily cumulative variation in NEE was "V" shaped， and the monthly cumulative changes in NEE， ecosystem respiration （Reco）， and gross primary productivity （GPP） were obviously different. Photosynthetically active radiation （PAR） was an important regulation factor of daytime NEE in the restored area in 2021， and they displayed a rectangular hyperbolic relationship. PAR could explain 53% of the variation in the daytime NEE. Air temperature （Ta） was the main control factor of Reco，night， and there was an exponential relationship between them. When Ta < 5.5 ℃， the temperature sensitivity of ecosystem respiration （Q10） was 2.19， and Ta could explain 42% of the variation in the Reco，night； when Ta ≥ 5.5 ℃， the Q10 was 1.81， and Ta could explain 51% of the variation in the Reco，night. Additionally， there were significant linear negative correlations between NEE and both soil water content （SWC） and vapor pressure deficit （VPD）， whereas NEE was not significantly correlated with soil temperature （Ts） or relative humidity （RH）. In 2021， the restored wetland in the Liaohe River estuary acted as a CO2 sink， and the total net carbon sequestration was -66.89 g·m-2. The restored salt plays a role as an important carbon sink and has long-term carbon sequestration potential.

Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver.

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.

BMS-794833 reduces anlotinib resistance in osteosarcoma by targeting the VEGFR/Ras/CDK2 pathway.

Background: Osteosarcoma, a tumor that originates from bone cells, has a poor prognosis and a high degree of malignancy. Anlotinib, a small-molecule multi-target tyrosine kinase inhibitor (TKI), is the first-line drug in treating osteosarcoma, especially in late-stage osteosarcoma. However, patients often develop resistance after using anlotinib for a certain period, which poses a challenge to its further clinical application. Recently, several TKIs, for instance regorafenib and cabozantinib, have showed clinical interest in treating osteosarcoma and target both vascular endothelial growth factor receptor (VEGFR) and mesenchymal epithelial transition factor (c-MET). Therefore, the identification of new TKI warrants further investigation. Methods: We performed CCK8 aasays to confirm that BMS-794833 sensitization osteosarcoma cells to anlotinib. Bioinformatics analysis and rescue experiments showed that the reduce of resistance were dependent on the VEGFR/Ras/CDK2 pathway. Cell line based xenograft model were used to demonstrate that BMS-794833 and anlotinib could synergistically treat OS. Results: Here, we found that BMS-794833 reduced anlotinib resistance in osteosarcoma by targeting the VEGFR/Ras/CDK2 pathway. CCK8 assay showed that BMS-794833 significantly improved the resistance of osteosarcoma cells to anlotinib. The results of rescue experiments showed that the regulatory effects of BMS-794833 on the proliferation and drug resistance of osteosarcoma cells were dependent on the VEGFR/Ras/CDK2 pathway. In addition, BMS-794833 affected the resistance of osteosarcoma cells to anlotinib through epithelial-mesenchymal transition (EMT) and apoptosis pathways. More importantly, BMS-794833 and anlotinib exerted synergistic therapeutic effects against osteosarcoma in vivo. Conclusion: Altogether, this study reveals a new (VEGFR)-targeting drug that can be combined with anlotinib for the treatment of osteosarcoma, which provides an important theoretical basis for overcoming anlotinib resistance.

Spontaneous coronary artery rupture after lung cancer surgery: A case report and review of literature.

BACKGROUND: Spontaneous coronary artery rupture (SCAR) is a rare and life-threatening complication after lung cancer surgery. We present a case of SCAR following left upper lobectomy, successfully managed through emergency thoracotomy and coronary artery ligation. CASE SUMMARY: A 61-year-old male patient underwent left upper lobectomy and mediastinal lymph node dissection for lung cancer. The surgery was performed using single-port video-assisted thoracoscopic surgery, and there were no observed complications during the procedure. However, 19 h after surgery, the patient experienced chest discomfort and subsequently developed severe symptoms, including nausea, vomiting, and a drop in blood pressure. Urgent measures were taken, leading to the diagnosis of SCAR. The patient underwent emergency thoracotomy and coronary artery ligation, successfully stopping the bleeding and stabilizing the condition. Despite postoperative complications, the patient made a successful recovery and was discharged from the hospital. CONCLUSION: SCAR is a rare but life-threatening complication following lung cancer surgery. Immediate thoracotomy has been shown to be a life-saving measure, while stenting is not the preferred initial approach.

Antibiotic residues in commercial freshwater fish from southeast China: distribution and human health risk assessment.

We investigated 14 antibiotic residues in 8 marketed freshwater fish species from southeast China and estimated the associated health risks to local consumers. The antibiotic residues were determined by UPLC-MS/MS. Our findings revealed widespread distribution of quinolones (QNs), tetracyclines (TCs), and chloramphenicols (CAPs) in the freshwater fish. Notably, the average concentrations of enrofloxacin and ciprofloxacin reached levels as high as 62.5 µg/kg wet weight (ww) and 11.7 µg/kg ww, respectively, and detection frequencies were 68.7% for enrofloxacin and 31.6% for ciprofloxacin. Additionally, we detected chloramphenicol, a prohibited antibiotic, in samples with a detection frequency of 0.76%. Among the fish species, the mean concentration of total antibiotic residues was highest in bluntnose black bream (263.3 µg/kg), followed by English perch (52.4 µg/kg), crucian carp (46.3 µg/kg), black carp (28.6 µg/kg), yellowcheek carp (21.0 µg/kg), grass carp (15.3 µg/kg), bighead carp (3.78 µg/kg), and mandarin fish (3.69 µg/kg). We estimated the daily intake values of these antibiotic residues which were lower than the acceptable daily intake values and hazard indexes were much less than 1. It indicates that there is very low direct health risk to consumers. Despite that, investigation on the chronic impact, such as antibiotic-resistant bacteria, gut microbiota disruption, and allergic reactions, is urgently needed.

Charge-Optimized Electrostatic Interaction Atom-Centered Neural Network Algorithm.

Machine-learning algorithms have been proposed to capture electrostatic interactions by using effective partial charges. These algorithms often rely on a pretrained model for partial charge prediction using density functional theory-calculated partial charges as references, which introduces complexity to the force field model. The accuracy of the trained model also depends on the reliability of charge partition methods, which can be dependent on the specific system and methodology employed. In this study, we propose an atom-centered neural network (ANN) algorithm that eliminates the need for reference charges. Our algorithm requires only a single NN model for each element to obtain both atomic energy and charges. These atomic charges are then employed to compute electrostatic energies using the Ewald summation algorithm. Subsequently, the force field model is trained on total energy and forces, with the inclusion of electrostatic energy. To evaluate the performance of our algorithm, we conducted tests on three benchmark systems, including a Ge slab with an O adatom system, a TiO2 crystalline system, and a Pd-O nanoparticle system. Our results demonstrate reasonably accurate predictions of partial charges and electrostatic interactions. This algorithm provides a self-consistent charge prediction strategy and possibilities for robust and reliable modeling of electrostatic interactions in machine-learning potentials.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver.

An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

Toward exclusive stereocomplex crystallization of high-molecular-weight poly(L-lactic acid)/poly(D-lactic acid) blends with outstanding heat resistance via incorporating selective nucleating agents.

In high molecular weight poly(L-lactic acid)/poly(D-lactic acid) (HMW PLLA/PDLA) blends, the construction of exclusive stereocomplex crystals (SC) with high crystallinity and strong melt memory remains a great challenge. In the present study, various norbornene dicarboxylate complexes (TMXNa, Mg, Al, or Ca) were employed as the stereo-selective nucleating agents (NAs), and their effect on the crystallization characteristics, rheological behavior, and heat resistance of PLLA/PDLA blends were thoroughly studied. Strikingly, TMX-Al facilitated the construction of exclusive SC with over 50 % crystallinity and excellent melt memory. The dense SC crystals network structure boosted the heat resistance of L/D-xAl blends with a VST as high as 145 °C. The strengthened intermolecular interaction fostered the generation of pre-ordered structure in the melt and enhanced chain interdiffusion, which contributed to intermolecular nucleation and SC crystallization in L/D-xAl blend. This study opens up a new avenue for melt processing and application development of SC-PLA materials.

Fluorescent imaging and toxicology study of alga-derived carbon dots in zebrafish.

With the widespread application of carbon dots (CDs) in fluorescence imaging, their toxicity has become a focal point of concern. The potential toxicity of CDs synthesized from different raw materials remains an unresolved issue. Laver and wakame, which are commonly popular sea vegetable foods rich in nutrients, were utilized to investigate whether synthetic CDs derived from these alga sources retain medicinal value. Herein, two types of fluorescent alga-derived CDs were prepared through hydrothermal synthesis using laver and wakame respectively. Zebrafish were immersed in both types of CDs to observe their fluorescence imaging effects within the zebrafish bodies. It was observed that laver-derived CDs and wakame-derived CDs exhibited similar luminescence properties but differed in terms of fish egg imaging localization. Additionally, intestinal flora sequencing revealed varying degrees of influence on the zebrafish gut microbiota by the two types of CDs, suggesting that both alga-derived CDs could enhance the abundance of intestinal flora in zebrafish.

Aggravated visual toxicity in zebrafish larvae upon co-exposure to titanium dioxide nanoparticles and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate.

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of ßB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates.