Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

Metal-Free Perovskite Ferroelectrics with the Most Equivalent Polarization Axes.

Ferroelectricity in metal-free perovskites (MFPs) has emerged as an academic hotspot for their lightweight, eco-friendly processability, flexibility, and degradability, with considerable progress including large spontaneous polarization, high Curie temperature, large piezoelectric response, and tailoring coercive field. However, their equivalent polarization axes as a key indicator are far from enough, although multiaxial ferroelectrics are highly preferred for performance output and application flexibility that profit from as many equivalent polarization directions as possible with easier reorientation. Here, by implementing the synergistic overlap of regulating anionic geometries (from spherical I- to octahedral [PF6]- and to tetrahedral [ClO4]- or [BF4]-) and cationic asymmetric modification, we successfully designed multiaxial MFP ferroelectrics CMDABCO-NH4-X3 (CMDABCO = N-chloromethyl-N'-diazabicyclo[2.2.2]octonium; X = [ClO4]- or [BF4]-) with the lowest P1 symmetry. More impressively, systemic characterizations indicate that they possess 24 equivalent polarization axes (Aizu notations of 432F1 and m3̅mF1, respectively)─the maximum number achievable for ferroelectrics. Benefiting from the multiaxial feature, CMDABCO-NH4-[ClO4]3 has been demonstrated to have excellent piezoelectric sensing performance in its polycrystalline sample and prepared composite device. Our study provides a feasible strategy for designing multiaxial MFP ferroelectrics and highlights their great promise for use in microelectromechanical, sensing, and body-compatible devices.

Beyond Single-Cycle Autonomous Molecular Machines: Light-Powered Shuttling in a Multi-Cycle Reaction Network.

Biomolecular machines autonomously convert energy into functions, driving systems away from thermodynamic equilibrium. This energy conversion is achieved by leveraging complex, kinetically asymmetric chemical reaction networks that are challenging to characterize precisely. In contrast, all known synthetic molecular systems in which kinetic asymmetry has been quantified are well described by simple single-cycle networks. Here, we report on a unique light-driven [2]rotaxane that enables the autonomous operation of a synthetic molecular machine with a multi-cycle chemical reaction network. Unlike all prior systems, the present one exploits a photoactive macrocycle, which features a different photoreactivity depending on the binding sites at which it resides. Furthermore, E to Z isomerization reverses the relative affinity of the macrocycle for two binding sites on the axle, resulting in a multi-cycle network. Building on the most recent theoretical advancements, this work quantifies kinetic asymmetry in a multi-cycle network for the first time. Our findings represent the simplest rotaxane capable of autonomous shuttling developed so far and offer a general strategy to generate and quantify kinetic asymmetry beyond single-cycle systems.

The spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil in the terrestrial ecosystem.

Carbon(C), nitrogen(N), and phosphorus(P) are crucial elements in the element cycling in the terrestrial ecosystems. In the past decades, the spatial pattern and driving mechanism of plant and soil ecological stoichiometry have been hot topics in ecological geography. So far, many studies at different spatial and ecological scales have been conducted, but systematic review has not been reported to summarize the research status. In this paper, we tried to fill this gap by reviewing both the spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil at regional to large scale. Additionally, we synthesized researches on the relationships between plant and soil C, N and P stoichiometric characteristics. At the global scale, plant C, N, P stoichiometric characteristics exhibited some trends along latitude and temperature gradient. Plant taxonomic classification was the main factor controlling the spatial variations of plant C, N and P stoichiometric characteristics. Climate factor and soil properties showed varying impacts on the spatial variations of plant C, N, P stoichiometric characteristics across different spatial scales. Soil C, N, P stoichiometric characteristics also vary along climate gradient at large scale. Their spatial variations result from the combined effects of climate, topography, soil properties, and vegetation characteristics at regional scale. The spatial pattern of soil C, N, P stoichiometric characteristics and the driving effects from environmental factors could be notably different among different ecosystems and vegetation types. Plant C:N:P is obviously higher than that of soil, and there exists a positive correlation between plant and soil C:N:P. Their trends along longitude and latitude are similar, but this correlation varies significantly among different vegetation types. Finally, based on the issues identified in this paper, we highlighted eight potential research themes for the future studies.

Clinical Significance of Long Non-Coding RNA SNHG5 in the Diagnosis and Prognosis of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is preventable and requires early screening. The study aimed to examine the clinical values of long non-coding RNA (lncRNA) SNHG5 in COPD diagnosis and prognosis. Out of 160 COPD patients, 80 were in the stable stage and 80 were in the acute exacerbation of COPD stage (AECOPD). SNHG5 expression was detected via qRT-PCR. The survival analysis was conducted using Cox regression analysis and K-M curve. SNHG5 levels significantly reduced in both stable COPD and AECOPD groups compared with the control group, with AECOPD group recording the lowest values. SNHG5 levels were negatively correlated with GOLD stage. Serum SNHG5 can differentiate stable COPD patients from healthy individuals (AUC = 0.805), and can screen AECOPD from stable ones (AUC = 0.910). SNHG5 negatively influenced the release of inflammatory cytokines. For AECOPD patients, those with severe cough and wheezing dyspnea symptoms exhibited the lowest values of SNUG5. Among the 80 AECOPD patients, 16 cases died in the one-year follow-up, all of whom had low levels of SNHG5. SNHG5 levels independently influenced survival outcomes, patients with low SNHG5 levels had a poor prognosis. Thus, lncRNA SNHG5, which is downregulated in patients with COPD (especially AECOPD), can potentially protect against AECOPD and serve as a novel prognostic biomarker for AECOPD.

Interfacial Distortion of Sb2Te3-Sb2Se3 Multilayers via Atomic Layer Deposition for Enhanced Thermoelectric Properties.

Atomic layer deposition (ALD) is an effective technique for depositing thin films with precise control of layer thickness and functional properties. In this work, Sb2Te3-Sb2Se3 nanostructures were synthesized using thermal ALD. A decrease in the Sb2Te3 layer thickness led to the emergence of distinct peaks from the Laue rings, indicative of a highly textured film structure with optimized crystallinity. Density functional theory simulations revealed that carrier redistribution occurs at the interface to establish charge equilibrium. By carefully optimizing the layer thicknesses, we achieved an obvious enhancement in the Seebeck coefficient, reaching a peak figure of merit (zT) value of 0.38 at room temperature. These investigations not only provide strong evidence for the potential of ALD manipulation to improve the electrical performance of metal chalcogenides but also offer valuable insights into achieving high performance in two-dimensional materials.

Biomethane recovery and prokaryotic shifts in anaerobic co-digestion of food waste and paper waste in organic fraction of municipal solid waste: Effect of paper content.

Biomethane recovery from paper waste (PW) was achieved by mesophilic co-digestion with food waste. The feeding material containing 0%, 20%, 40% and 50% of PW in total solids (TS) were investigated in the long-term continuous operation. The results showed that the biogas production, pH, alkalinity and biodegradation of volatile solids (79.8 ± 3.6%) were stable for PW contents no more than 50%. The PW = 50% condition was considered the critical limit for the reasons of pump clogging, sufficient alkalinity (2.0 ± 0.3 g-CaCO3/L) and depletion of ammonia. Prokaryotic diversity indices decreased with the increased PW contents. Great shifts were observed in the prokaryotic communities before and after the PW contents reaches 50% as TS (18.4% as total weights). Biomethane recovery yields were deceasing from 445 to 350 NL-CH4/kg-fed-volatile-solids. The PW contents as 40% as TS (13.1% as total weights) obtained the optimal performance among all the feeding conditions.

In Situ Fabrication of High Ionic and Electronic Conductivity Interlayers Enabling Long-Life Garnet-Based Solid-State Lithium Batteries.

Garnet-type Li6.75La3Zr1.75Ta0.25O12 (LLZTO) is a promising solid-state electrolyte (SSE) because of its fast ionic conduction and notable chemical/electrochemical stability toward the lithium (Li) metal. However, poor interface wettability and large interface resistance between LLZTO and Li anode greatly restrict its practical applications. In this work, we develop an in situ chemical conversion strategy to construct a highly conductive Li2S@C layer on the surface of LLZTO, enabling improved interfacial wettability between LLZTO and the Li anode. The Li/Li2S@C-LLZTO-Li2S@C/Li symmetric cell has a low interface impedance of 78.5 Ω cm2, much lower than the 970 Ω cm2 of a Li/LLZTO/Li cell. Moreover, the Li/Li2S@C-LLZTO-Li2S@C/Li cell exhibits a high critical current density of 1.4 mA cm-2 and an ultralong stability of 3000 h at 0.1 mA cm-2. When used in a LiFePO4 battery, the Li/Li2S@C-LLZTO/LiFePO4 battery exhibits a high initial discharge capacity of 150.8 mA h g-1 at 0.2 C without lithium storage capacity attenuation during 200 cycles. This work provides a novel and feasible strategy to address interface issues of SSEs and achieve lithium-dendrite-free solid-state batteries.

Design and Implementation of an Intensive Care Unit Command Center for Medical Data Fusion.

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.

[Influence of telemedicine on the operation of public hospitals in China].

OBJECTIVE: Telemedicine, as an information-based tool, is widely recognized as an effective solution for compensating for the imbalanced allocation of medical resources in China. This study specifi-cally aimed to analyze the impact of telemedicine functions on the operational efficiency of public hospitals, with a particular focus on their heterogeneous effects on hospitals of different levels. METHODS: A cross-sectional research design was used based on the 2022 Health Informatization Statistical Survey data, and 8 944 public hospitals were used as research objects to analyze the impact of telemedicine on hospital revenues and business capacity. Multivariate linear model, propensity score matching (PSM), and grouped regression methods were employed to evaluate the impact of telemedicine on hospital revenues, number of consultations, and the number of discharges. RESULTS: The descriptive results showed that telemedicine was available in 35.51% of public hospitals. The analysis also demonstrated that various factors, such as hospital level, academic category, area of the hospital, administrational level and number of beds all had a significant influence on the operation of the hospital. Moreover, the regression results showed that opening telemedicine could increase hospital revenues by 0.140 (P < 0.01), hospital consultations by 0.136 (P < 0.01), and the number of discharges by 0.316 (P < 0.01). After correcting for endogeneity using the propensity score matching, the results showed that the effect of opening telemedicine on hospital revenues, consultations, and the number of discharges was 0.191 (P < 0.01), 0.216 (P < 0.01), and 0.353 (P < 0.01), respectively. Further heterogeneity analysis was conducted to explore the differential effects of telemedicine on hospitals of different levels. Grouped regression showed that telemedicine had a positive impact on the income of secondary hospitals, with a coefficient of 0.088 (P < 0.05), and it had a more significant positive impact on hospital consultations in secondary hospitals, with a coefficient of 0.127 (P < 0.01). An even greater impact on the number of discharges in primary hospitals, with a coefficient of 1.203 (P < 0.01). Telemedicine, on the other hand, did not have a significant positive impact on the overall revenue and operational capacity of tertiary hospitals. CONCLUSION: Telemedicine had a significant promoting effect on hospital revenues, hospital consultations and the number of discharges, and this effect was differentiated between hospitals of different levels. Through the construction of telemedicine, primary hospitals were able to significantly improve their business capacity and revenue, which played a positive role in improving the operation of primary public hospitals.

RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: To investigate the protective effect and possible mechanisms of vitamin B 6 against renal injury in patients with sepsis. Methods: A total of 128 patients with sepsis who met the entry criteria in multiple centers were randomly divided into experimental (intravenous vitamin B 6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen, serum creatinine, and renal resistance index monitored by ultrasound) were compared between the two groups. Results: After 7 d of treatment, the IL-6, IL-8, TNF-α, and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the blood urea nitrogen, serum creatinine, and renal resistance index values in the experimental group were significantly lower than those in the control group ( P < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( P > 0.05). However, the intensive care unit length of stay and the total hospitalization expenses in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The administration of vitamin B 6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.

Hierarchical porous carbon materials for lithium storage: preparation, modification, and applications.

Secondary battery as an efficient energy conversion device has been highly attractive for alleviating the energy crisis and environmental pollution. Hierarchical porous carbon (HPC) materials with multiple sizes pore channels are considered as promising materials for energy conversion and storage applications, due to their high specific surface area and excellent electrical conductivity. Although many reviews have reported on carbon materials for different fields, systematic summaries about HPC materials for lithium storage are still rare. In this review, we first summarize the main preparation methods of HPC materials, including hard template method, soft template method, and template-free method. The modification methods including porosity and morphology tuning, heteroatom doping, and multiphase composites are introduced systematically. Then, the recent advances in HPC materials on lithium storage are summarized. Finally, we outline the challenges and future perspectives for the application of HPC materials in lithium storage.

Enhancing sludge dewaterability in sequential bioleaching: Degradation of dissolved organic matter (DOM) by filamentous fungus Mucor sp. ZG-3 and the influence of energy source.

This study aimed to enhance sludge dewatering through sequential bioleaching, employing the filamentous fungus Mucor sp. ZG-3 and the iron-oxidizing bacterium Acidithiobacillus ferrooxidans LX5. The mechanism by which Mucor sp. ZG-3 alleviates sludge dissolved organic matter (DOM) inhibition of A. ferrooxidans LX5 was investigated, and the optimal addition of energy source for enhanced sludge dewaterability during sequential bioleaching was determined. Sludge dissolved organic carbon (DOC) decreased to 272 mg/L with a 65.2% reduction by Mucor sp. ZG-3 in 3 days, and the degraded fraction of sludge DOM was mainly low-molecular-weight DOM (L-DOM) which inhibited the oxidization of Fe2+ by A. ferrooxidans LX5. By degrading significant inhibitory low-molecular-weight organic acids, Mucor sp. ZG-3 alleviated DOM inhibition of A. ferrooxidans LX5. In the sequential bioleaching process, the optimal concentration of FeSO4·7H2O for A. ferrooxidans LX5 was 4 g/L, resulting in the minimum specific resistance to filtration (SRF) of 2.60×1011 m/kg, 40.0% lower than that in the conventional bioleaching process with 10 g/L energy source. Moreover, the sequential bioleaching process increased the sludge zeta potential (from -31.8 to -9.47 mV) and median particle size (d50) of the sludge particle (from 17.90 to 27.44 µm), contributing to enhanced sludge dewaterability. Inoculation of Mucor sp. ZG-3 during the bioleaching process reduced the demand for energy sources by A. ferrooxidans LX5 while improving sludge dewaterability performance.

Eggshell-Like Carbon Microspheres with Curvature Scheme: Distorted Energy Band and Atomic Charge Waves-Driven High Performance for Zinc-Air Battery.

A metal-free nanocarbon with an eggshell structure is synthesized from chitosan (CS) and natural spherical graphite (NSG) as a cathode electrocatalyst for clean zinc-air batteries and fuel cells. It is developed using CS-derived carbons as an eggshell, covering NSG cores. The synthesis involves the in situ growth of CS on NSG, followed by ammonia-assisted pyrolysis for carbonization. The resulting catalyst displays a curved structure and completely coated NSG, showing superior oxygen reduction reaction (ORR) performance. In 1 M NaOH, the ORR half-wave potential reached 0.93 V, surpassing the commercial Pt/C catalyst by 50 mV. Furthermore, a zinc-air battery featuring the catalyst achieves a peak power density of 167 mW cm-2 with excellent stability, outperforming the Pt/C. The improved performance of the eggshell carbons can be attributed to the distorted energy band of the active sites in the form of N-C moieties. More importantly, the curved thin eggshells induce built-in electric fields that can promote electron redistribution to generate atomic charge waves around the N-C moieties on the carbon shells. As a result, the high positively charged and stable C+ sites adjacent to N atoms optimize the adsorption strength of oxygen molecules, thereby facilitating performance.

Spider-silk-inspired strong and tough hydrogel fibers with anti-freezing and water retention properties.

Ideal hydrogel fibers with high toughness and environmental tolerance are indispensable for their long-term application in flexible electronics as actuating and sensing elements. However, current hydrogel fibers exhibit poor mechanical properties and environmental instability due to their intrinsically weak molecular (chain) interactions. Inspired by the multilevel adjustment of spider silk network structure by ions, bionic hydrogel fibers with elaborated ionic crosslinking and crystalline domains are constructed. Bionic hydrogel fibers show a toughness of 162.25 ± 21.99 megajoules per cubic meter, comparable to that of spider silks. The demonstrated bionic structural engineering strategy can be generalized to other polymers and inorganic salts for fabricating hydrogel fibers with broadly tunable mechanical properties. In addition, the introduction of inorganic salt/glycerol/water ternary solvent during constructing bionic structures endows hydrogel fibers with anti-freezing, water retention, and self-regeneration properties. This work provides ideas to fabricate hydrogel fibers with high mechanical properties and stability for flexible electronics.

A molecular sheaf: doubly threaded [6]rotaxane.

We report that the use of a hydrogen-bonded pyrimidine-macrocycle complex can efficiently facilitate the threading of two bispyridinium ethylenes into four rings, as evidenced by X-ray crystallography of its precursor, offering a rare example of a doubly threaded [6]rotaxane in 91% yield. The unusual architecture is found to be stable with no dethreading despite the large ring size of the macrocycle with respect to the stopper.

Influence of magnetic field on electron beam-induced Coulomb explosion of gold microparticles in transmission electron microscopy.

In this work we instigated the fragmentation of Au microparticles supported on a thin amorphous carbon film by irradiating them with a gradually convergent electron beam inside the Transmission Electron Microscope. This phenomenon has been generically labeled as "electron beam-induced fragmentation" or EBIF and its physical origin remains contested. On the one hand, EBIF has been primarily characterized as a consequence of beam-induced heating. On the other, EBIF has been attributed to beam-induced charging eventually leading to Coulomb explosion. To test the feasibility of the charging framework for EBIF, we instigated the fragmentation of Au particles under two different experimental conditions. First, with the magnetic objective lens of the microscope operating at full capacity, i.e. background magnetic field B=2 T, and with the magnetic objective lens switched off (Lorenz mode), i.e. B=0 T. We observe that the presence or absence of the magnetic field noticeably affects the critical current density at which EBIF occurs. This strongly suggests that magnetic field effects play a crucial role in instigating EBIF on the microparticles. The dependence of the value of the critical current density on the absence or presence of an ambient magnetic field cannot be accounted for by the beam-induced heating model. Consequently, this work presents robust experimental evidence suggesting that Coulomb explosion driven by electrostatic charging is the root cause of EBIF.

[Summary and evaluation of randomized controlled trial on Chinese patent medicine in treatment of diabetic foot ulcer].

This study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) in the treatment of diabetic foot ulcer(DFU). The aim as provide references for future studies and to enhance the application of clinical evidence. The RCT of DFU treated with Chinese Patent Medicine was obtained and analyzed using the AI-Clinical Evidence Database of Chinese Patent Medicine(AICED-CPM). The analysis was supplemented with data from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science. A total of 275 RCTs meeting the requirements were retrieved, with only 7 of them having a sample size of 200 or more. These trials involved 66 different Chinese patent medicine including 25 oral medications, 24 Chinese herbal injections, and 17 external drugs. Among the 33 different intervention/control designs identified, the most common design was Chinese patent medicine + conventional treatment vs conventional treatment(86 cases, 31.27%). Out of the 275 articles included in the literature, 50 did not provide information on the specific course of treatment(18.18%). A total of 10 counting indicators(with a frequency of 426) and 36 measuring indicators(with a frequency of 962) were utilized. The methodological quality of the RCT for the treatment of DFU with Chinese patent medicine was found to be low, with deficiencies in blind methods, other bias factors, study registration, and sample size estimation. There were noticeable shortcomings in the reporting of allocation hiding and implementation bias(blind method application). More studies should prioritize trial registration, program design, and strict quality control during implementation to provide valuable data for clinical practice and serve as a reference for future investigations.

Evaluation of sub-chronic toxicity of melamine via systematic or oral delivery in adult zebrafish based on behavioral endpoints.

Melamine-tainted products have been found in the market and raised issues about food safety. Recent studies done in rodents and humans demonstrated the toxicities of melamine, especially in causing kidney damage and bladder stone formation. However, very few studies assessed its behavior toxicity in organisms, including fish. Therefore, in this study, the researchers aim to determine whether sub-chronic exposure to melamine via oral and systematic administration could induce behavioral abnormality in zebrafish. After 14 days of systematic exposure to melamine at doses of 0.1 and 10 ppm levels, zebrafish were subjected to multiple behavioral assays. Results from both exposure routes showed that melamine indeed slightly increased fish locomotion and altered their exploratory behaviors in the novel tank assay. Furthermore, tightened shoaling formation was also displayed by the treated fish in the waterborne exposure group. However, melamine exposure did not cause any obvious alterations in fish behaviors during other behavioral tests. In addition, in comparison with previously published data on the behavior toxicities of several solvents in zebrafish, our phenomic analysis suggests the relatively low behavior toxicities of melamine via either systematic exposure or oral administration to zebrafish compared to those solvents. Nevertheless, our data indicate that the potential neurotoxicity of chronic low-dose melamine should not be ignored.