NURR1 expression regulates retinal pigment epithelial-mesenchymal transition and age-related macular degeneration phenotypes.

Phenotypic variations in the retinal pigment epithelial (RPE) layer are often a predecessor and driver of ocular degenerative diseases, such as age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We previously identified the orphan nuclear receptor-related 1 (NURR1), from a nuclear receptor atlas of human RPE cells, as a candidate transcription factor potentially involved in AMD development and progression. In the present study we characterized the expression of NURR1 as a function of age in RPE cells harvested from human donor eyes and in donor tissue from AMD patients. Mechanistically, we found an age-dependent shift in NURR1 dimerization from NURR1-RXRα heterodimers toward NURR1-NURR1 homodimers in primary human RPE cells. Additionally, overexpression and activation of NURR1 attenuated TNF-α-induced epithelial-to-mesenchymal transition (EMT) and migration, and modulated EMT-associated gene and protein expression in human RPE cells independent of age. In vivo, oral administration of IP7e, a potent NURR1 activator, ameliorated EMT in an experimental model of wet AMD and improved retinal function in a mouse model that presents with dry AMD features, impacting AMD phenotype, structure, and function of RPE cells, inhibiting accumulation of immune cells, and diminishing lipid accumulation. These results provide insight into the mechanisms of action of NURR1 in the aging eye, and demonstrate that the relative expression levels and activity of NURR1 is critical for both physiological and pathological functions of human RPE cells through RXRα-dependent regulation, and that targeting NURR1 may have therapeutic potential for AMD by modulating EMT, inflammation, and lipid homeostasis.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Encoding independent wavefronts in a single metasurface for high-order optical vortex recognition.

The orbital angular momentum (OAM) of vortex beams has great potential in optical communications due to its communication confidentiality and low crosstalk. It is necessary to design a plausible OAM pattern recognition mechanism. Abandoning AI models that require large datasets, a single passive all-dielectric metasurface consisting of TiO2 nanopillars on a SiO2 substrate is used to recognize high-order optical vortexes. In this configuration, the proposed device is capable of simultaneously encoding the wavefront and the transmission paths in different incident OAM beams. Due to the presence of spin angular momentum (SAM), the vortex beam to be identified is spatially separated after passing through the metasurface. As a proof of concept, 14 signal channels are considered in the constructed metasurface, 12 of them can be encoded at will for the detection of any vortex beam with a predefined topological charge. These results make use of metasurfaces to enable OAM pattern recognition in an effective way, which may open avenues for the ultimate miniaturization of optical vortex communication and advanced OAM detection technologies.

Experimental investigation on the internal stress of bismuth-doped fiber and its effect on the noise figure of Bismuth-doped fiber amplifier.

The noise figure (NF) of a fiber amplifier is one of the key measures of amplification performance, which characterizes the quality of the amplified signal. Residual stresses are inevitably generated during the manufacturing process of optical fibers, and this can lead to changes in the refractive index (RI) distribution of the fiber. Further, the change in RI distribution causes the mode-field characteristics of the fiber to change as well, and this ultimately has an impact on the NF performance of the amplifier. However, until now, there have been fewer studies on the effect of residual stress on the NF of the fiber amplifiers. In this work, we took a commercial single-mode bismuth-doped fiber (BDF) as an example and used a self-developed stress test device to measure its residual stress and refractive index distribution and compare it with that of a passive fiber. We also comprehensively compared the distribution of residual stress and refractive index of the fiber at different pump powers and pump wavelengths. Finally, we performed numerical simulations of the bismuth-doped fiber amplifier (BDFA) based on the BDF under the theoretical mode field area and BDF after the expansion of the mode field area due to stresses to compare the NF performance. The results demonstrate that: the entire cross-section (core and cladding) of the BDF exhibits tensile stress (>0 MPa), where the residual stress at the core of the BDF is nearly 9.8 MPa higher than that of the passive fiber; The residual stress makes the mode-field area of the BDF expand by 26.7% compared with the theoretical values, which ultimately makes the NF of the BDFA rise from 4.6 dB to 4.7 dB; The stress at the BDF core is exacerbated by pump excitation, where it is elevated by about 26% and 5% compared to vacancy at 1240 nm and 1310 nm pumps, which is most likely attributed to thermal effects. Therefore, it is necessary to consider the effect of residual stresses in the fabrication of optical fibers to better achieve the radius of the expected indicators. This work contributes to the better development of O-band BDFAs, especially for pre-simulation of the actual performance of BDFAs with a practical reference.

Photonic delay reservoir computer based on ring resonator for reconfigurable microwave waveform generator.

To achieve an autonomously controlled reconfigurable microwave waveform generator, this study proposes and demonstrates a self-adjusting synthesis method based on a photonic delay reservoir computer with ring resonator. The proposed design exploits the ring resonator to configure the reservoir, facilitating a nonlinear transformation and providing delay space. A theoretical analysis is conducted to explain how this configuration addresses the challenges of microwave waveform generation. Considering the generalization performance of waveform generation, the simulations demonstrate the system's capability to produce six distinct representative waveforms, all exhibiting a highly impressive root mean square error (RMSE) of less than 1%. To further optimize the system's flexibility and accuracy, we explore the application of various artificial intelligence algorithms at the reservoir computer's output layer. Furthermore, our investigation delves deeply into the complexities of system performance, specifically exploring the influence of reservoir neurons and micro-ring resonator parameters on calculation performance. We also delve into the scalability of reservoirs, considering both parallel and cascaded arrangements.

Bismuth-doped fiber amplifier based on a linear cavity double pass structure operating in the O + E band.

Finding suitable fiber amplifiers is one of the key strategies to increase the transmission capacity of fiber links. Recently, bismuth-doped fiber amplifiers (BDFAs) have attracted much attention due to their distinctive ultra-wideband luminescence properties. In this paper, we propose a linear cavity double pass structure for BDFA operating in the O and E bands. The design creates a linear cavity within the amplifier by combining a fiber Bragg grating (FBG) and a fiber mirror to achieve dual-wavelength pump at 1240 nm and 1310 nm. Meanwhile, the configuration of a circulator and mirror facilitates bidirectional signal propagation through the BDFA, resulting in a double-pass amplification structure. We have tested and analyzed the performance of the linear cavity double pass structure BDFA under different pump schemes and compared it with the conventional structure BDFA. The results show that the gain spectrum of the new structure is shifted toward longer wavelengths, and the gain band is extended from the O band to the O and E bands compared with the conventional structure. In particular, the linear cavity double pass structure BDFA has more relaxed requirements on the stability of the pump and signal power. This work provides a positive reference for the design, application, and development of BDFAs.

Channelized multi-frequency measurement system based on asymmetric double sideband detection.

A channelized multi-frequency measurement system based on asymmetric double sideband detection is proposed. In this scheme, the sub-modulators of the dual-parallel Mach-Zehnder modulator are utilized for optical frequency comb (OFC) generation and under-test signal modulation. Subsequently, a sawtooth wave voltage is applied to the main modulator to introduce frequency shift to the modulated signals, breaking the symmetry between the RF signals and the OFC. The coupled signal is then divided into upper and lower sidebands for frequency down-conversion. By calibrating the measurement results of the two sidebands with each other, the frequency of the signal can be accurately measured. Simulation is preformed to realize multi-frequency measurement of microwave signals with measurement error less than 2 MHz in the range of 2.2-20 GHz. It is also found that the proposal can solve the problem of frequency ambiguity.

Isoalantolactone exerts anti-melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models.

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

Modulating Photoinduced Electron Transfer between Photosensitive MOF and Co(II) Proton Reduction Sites for Boosting Photocatalytic Hydrogen Production.

Photocatalytic hydrogen production via water splitting is the subject of intense research. Photoinduced electron transfer (PET) between a photosensitizer (PS) and a proton reduction catalyst is a prerequisite step and crucial to affecting hydrogen production efficiency. Herein, three photoactive metal-organic framework (MOF) systems having two different PET processes where PS and Co(II) centers are either covalently bonded or coexisting to drive photocatalytic H2 production are built. Compared to these two intramolecular PET systems including CoII -Zn-PDTP prepared from the post-synthetic metalation toward uncoordinated pyridine N sites of Zn-PDTP and sole cobalt-based MOF Co-PDTP, the CoII (bpy)3 @Zn-PDTP system impregnated by molecular cocatalyst possessing intermolecular PET process achieves the highest H2 evolution rate of 116.8 mmol g-1 h-1 over a period of 10 h, about 7.5 and 9.3 times compared to CoII -Zn-PDTP and Co-PDTP in visible-light-driven H2 evolution, respectively. Further studies reveal that the enhanced photoactivity in CoII (bpy)3 @Zn-PDTP can be ascribed to the high charge-separation efficiency of Zn-PDTP and the synergistic intermolecular interaction between Zn-PDTP and cobalt complexes. The present work demonstrates that the rational design of PET process between MOFs and catalytic metal sites can be a viable strategy for the development of highly efficient photocatalysts with enhanced photocatalytic activities.

The causal role of gut microbiota in susceptibility and severity of COVID-19: A bidirectional Mendelian randomization study.

Growing evidence has shown that altered gut microbiota is associated with the pathogenesis of COVID-19, but their causal effects are still unclear. We conducted a bidirectional Mendelian randomization (MR) study to assess the causal effects of gut microbiota on COVID-19 susceptibility or severity, and vice versa. The microbiome genome-wide association studies (GWAS) data of 18 340 individuals and GWAS statistics from the COVID-19 host genetics initiative (38 984 European patients and 1 644 784 controls) were used as exposure and outcomes. The inverse variance weighted (IVW) was used as the primary MR analysis. Sensitivity analyses were performed to validate the robustness, pleiotropy, and heterogeneity of results. In the forward MR, we identified several microbial genera with causal effects on COVID-19 susceptibility (p < 0.05 and FDR < 0.1): Alloprevotella (odds ratio [OR]: 1.088, 95% confidence interval [CI]: 1.021-1.160), Coprococcus (OR: 1.159, 95% CI: 1.030-1.304), Parasutterella (OR: 0.902, 95% CI: 0.836-0.973), and Ruminococcaceae UCG014 (OR: 0.878, 95% CI: 0.777-0.992). The Reverse MR identified that exposure to COVID-19 had causal effects on the depletion of the families Lactobacillaceae (Beta [SE]: -0.220 [0.101]) and Lachnospiraceae (-0.129 [0.062]), the genera Flavonifractor (-0.180 [0.081]) and Lachnoclostridium [-0.181 [0.063]). Our findings supported the causal effect of gut microbiota on the pathogenesis of COVID-19, and infection of COVID-19 might further causally induce gut microbiota dysbiosis.

High vapour pressure deficit enhances turgor limitation of stem growth in an Asian tropical rainforest tree.

Tropical forests are experiencing increases in vapour pressure deficit (D), with possible negative impacts on tree growth. Tree-growth reduction due to rising D is commonly attributed to carbon limitation, thus overlooking the potentially important mechanism of D-induced impairment of wood formation due to an increase in turgor limitation. Here we calibrate a mechanistic tree-growth model to simulate turgor limitation of radial stem growth in mature Toona cilitata trees in an Asian tropical forest. Hourly sap flow and dendrometer measurements were collected to simulate turgor-driven growth during the growing season. Simulated seasonal patterns of radial stem growth matched well with growth observations. Growth mainly occurred at night and its pre-dawn build-up appeared to be limited under higher D. Across seasons, the night-time turgor pressure required for growth was negatively related to previous midday D, possibly due to a relatively high canopy conductance at high D, relative to stem rehydration. These findings provide the first evidence that tropical trees grow at night and that turgor pressure limits tree growth. We suggest including turgor limitation of tree stem growth in models also for tropical forest carbon dynamics, in particular, if these models simulate effects of warming and increased frequency of droughts.

Light manipulation for all-fiber devices with VCSEL and graphene-based metasurface.

Light manipulation for all-fiber devices has played a vital role in controllable photonic devices. A graphene-based metasurface is proposed to realize light manipulation. A row of VCSEL-based optical engines with low crosstalk is used as the control light to modulate the signal transmitted in the microstructured fiber. In this configuration, the proposed device can work independently of the wavelength division multiplexing (WDM) system. With an insertion loss of only 0.28 dB, evanescent wave coupling to graphene layers is polarisation-insensitive. The device could be effectively manipulated for a few days (not less than 72 hours), which possesses the capacity to dynamically modulate the signal light with both low-temperature sensitivity and low-wavelength sensitivity. The 35 nm wavelength interval results in a change of only about 0.1 dB in the output light intensity of the microstructured fiber when the wavelength changes from 1530 nm to 1565 nm. Moreover, the modulation depth is approximately 2 dB when the modulating voltage is 2.2 V, which may open avenues for channel detection techniques and have deep implications in top tuning applications.

Traceless encryption approach for physical layer security in coherent optical communications system.

We proposed and numerically studied a traceless encryption approach for physical layer security in coherent optical communications system, the most attractive advantage of which is that it is hard for eavesdroppers to be aware that the transmission signal has been encrypted because the modulation formats of encrypted signal are still the regular ones, i.e. traceless encryption. In the proposed approach, the phase only or the combination of phase and amplitude dimensions can be used for encryption and decryption. Three simple encryption rules are designed and used to investigate the encryption security performance of the scheme, in which the QPSK signal can be encrypted to be as 8PSK, QPSK and 8QAM. The results show that three simple encryption rules can cause 37.5%, 25%, 62.5% of user signal binary codes to be misinterpreted by the eavesdroppers, respectively. When the modulation formats of encrypted signal and user signal are identical, the scheme can not only cover up the real information, but also have a potential application at misleading eavesdroppers. The impacts of the control light peak power at the receiver on the decryption performance are also analysed, the results indicate that the decryption performance of the scheme has a good tolerance to the peak power fluctuation of control light at the receiver.

Influencing factors of self-disclosure and its impact on quality of life in patients with systemic lupus erythematosus.

BACKGROUND: Self-disclosure may enhance positive illness perceptions, whereas patients with systemic lupus erythematosus (SLE) always facing negative illness perceptions due to multiple reasons, so elucidation of factors affecting self-disclosure may facilitate the development of quality of life. METHODS: A total of 161 hospitalized patients with SLE were recruited. Scales on demographic and clinical characteristics, self-disclosure, psychosocial status (e.g. Social Support Rating Scale - SSRS) and quality of life were used to collect related information from clients. Univariate analysis was performed by Kruskal-Wallis rank-sum test or chi-square test, and multivariate analysis by ordinal logistic regression. RESULTS: Social support, drinking, depression and cause of hospitalization were found to be influencing factors of self-disclosure. Multiple logistic regression analyses revealed that the significant and independent factors associated with self-disclosure in patients with SLE were social support, drinking and depression. Domains of LupusQoL, except physical health and fatigue, were positively correlated with self-disclosure. CONCLUSIONS: With the increase of social support, the level of self-disclosure become worse, drinking, depression and cause of hospitalization are risk factors for it. Moreover, the level of self-disclosure is positively related to the LupusQoL. Medical staff should formulate effective measures according to the results to improve self-disclosure in patients with SLE and promote their quality of life.

Eosin Y-Based Metal-Organic Framework Synergistic with Cobalt(II) Complex for Hydrogen Evolution through Photoinduced Intermolecular Electron Transfer.

Photocatalytic hydrogen evolution reaction (HER) is a promising approach for producing clean energy and has the potential to play an important role in the transition toward a more sustainable and environmentally friendly energy system. Optimizing the photoinduced electron transfer (PET) process and increasing visible-light utilization play a central role in photocatalysis. Herein, we built a novel Eosin Y-based metal-organic framework (Zn-EYTP) by synergizing a cobalt(II) complex for boosting the H2 evolution efficiency through photoinduced intermolecular electron transfer. Under optimized conditions, the maximum H2 evolution efficiency for Zn-EYTP was determined to be a turnover number (TON) value of 11,100 under green LED irradiation. And the synthesized Zn-EYTP photocatalysts could be easily recycled to restore the initial photocatalytic activity even after 3 cycles. Detailed studies reveal that the significantly enhanced HER activity in Zn-EYTP could be ascribed to the effective separation of photogenerated charges and the synergistic intermolecular interaction between Zn-EYTP and [Co(bpy)3]Cl2. The present work enables a deeper understanding of the importance of the PET process for enhanced HER photocatalytic activities, which will provide a viable strategy for the development of highly efficient photocatalysts.

Design of few-mode erbium-doped fiber with a low differential modal gain and weak coupling based on layered doping.

A step index few-mode erbium-doped fiber (FM-EDF) for mode gain equalization is designed and proposed in this paper, which uses the layered-doping method to reduce the differential mode gain (DMG). The optimum structure of FM-EDF is obtained by adjusting the doping radius and doping concentration. When this structure is applied to a few-mode erbium-doped fiber amplifier (FM-EDFA), the DMG in the range of 1550-1565 nm is ∼0.28d B, and the DMG of the whole C-band is usually less than 0.5 dB. At the same time, the gain of each mode in 1530-1555 nm is ∼20d B, while the gain decreases gradually in the 1555-1565 nm due to the absorption characteristics of erbium ions. In addition, the minimum refractive index difference (Δ n eff) between modes is 1.29∗10-3 due to the selection of the refractive index and radius of the fiber core, which will greatly reduce the coupling between modes in practical application. Tolerances in the fiber manufacturing process are also considered for reliable FM-EDFA performance. When the doping concentration or the doping radius changes based on the precise value, the DMG will increase to a certain extent. In general, the DMG can maintain a small value, which is beneficial to applications in optical communication systems.

Photonic generation of triangular waveform with tunable symmetry based on channelized frequency synthesis.

A symmetry tunable triangular waveform photonic generator based on channelized frequency synthesis is proposed and studied. The generator adopts a multichannel system architecture and harmonic amplitude control algorithm to physically isolate each subchannel. In a single subchannel, quadrature phase shift keying modulation and coherent dual-wavelength balanced detection are used to realize optical upconversion and suppress mixing interference in the process of frequency conversion. Therefore, the model has the characteristics of a high-order Fourier series fitting tunable function waveform output. The analysis results show that the Fourier series harmonic coefficients can be adjusted flexibly by the multivariable joint regulation algorithm. The relationship between the variables is analyzed and discussed. The feasibility of the scheme is verified by optical simulation; when the rms error (RMSE)≤0.03, a 20%-80% tunable symmetry triangular waveform can be obtained.

Self-similar pulse compression in a tapered Pb-silicate photonic crystal fiber at 2 µm.

We report a 2-µm all-fiber nonlinear pulse compressor based on a tapered Pb-silicate photonic crystal fiber (PCF), which is capable of achieving large compression with low pedestal energy. A tapered Pb-silicate photonic crystal fiber with increased nonlinear coefficients is proposed for achieving self-similar pulse compression (SSPC) at 2 µm. The dynamic evolution of the fundamental order soliton is numerically analyzed based on the designed tapered fiber. After pulse compression in a tapered fiber with a length of 2.2 m, an initial 1.76 ps pulse can be compressed to 88 fs, increasing the peak power from 4.4 to 86 W with a compression factor of 20 and a quality factor of 98%. The results reveal that exponential variation yields superior compression performance and provides a promising solution for generating high-power femtosecond pulses at 2 µm.

Natural mineral fibers: conducting inhalation toxicology studies-part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol.

BACKGROUND: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. RESULTS: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. CONCLUSION: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development.

BACKGROUND: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. RESULTS: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. CONCLUSIONS: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.