T-2 toxin-induced testicular impairment by triggering oxidative stress and ferroptosis.

T-2 toxin is a trichothecene mycotoxin of significant danger to humans and animals. Its impact on reproductive toxicity is attributed to oxidative stress, which ultimately leads to cell death. Ferroptosis is a programmed cell death that characterized by lipid peroxidation. This study aimed to investigate the toxic effects of T-2 toxin on mouse testis and the potential mechanism of T-2 toxin-induced ferroptosis. T-2 toxin significantly altered the morphology of the testis and decreased testosterone level, sperm concentration, and increased sperm malformation rate, as well as induced oxidative damage with reactive oxygen species and malondialdehyde accumulated, and activity of superoxide dismutase, glutathione peroxidase decreased. Additionally, T-2 toxin induced ferroptosis by accumulating iron ions, increasing prostaglandin endoperoxide synthase 2, downregulating glutathione peroxidase 4 and ferritin heavy chain 1, as well as manifesting ferroptotic morphological alterations, ultimately leading to testicular impairment. Administration of ferroptosis inhibitor liproxstatin-1 or antioxidant resveratrol effectively mitigated the T-2 toxin-induced ferroptosis and testicular injury. These findings provided novel insights into the fundamental mechanism of T-2 toxin-induced cell death and furnished further proof of the potential therapeutic effect in addressing T-2 toxin-induced testicular impairment.

Estimating the direction of arrival of spatially spread sources using block-sparse Bayesian learning with an extended dictionary.

Estimating the direction of arrival (DOA) of spatially spread sources is a significant challenge in array signal processing. This work introduces an effective method within the sparse Bayesian framework to tackle this issue. A spatially spread source is modeled using a multi-dimensional Slepian signal subspace that expands the dictionary and results in a block-sparse structured solution. By taking advantage of block-sparse Bayesian learning, parameter estimation becomes feasible. A complex Gaussian posterior is derived under a multi-snapshot block-sparse framework with a complex Gaussian prior and varying noise conditions. The hyperparameters are estimated using the expectation-maximization algorithm. Through numerical tests and sea test data evaluations, the proposed method shows superior energy focusing for spatially spread signals. Under limited snapshots and challenging signal-to-noise ratios, the current method can still offer precise DOA determination for spatially spread sources.

Laser waterless cleaning of residual organic solvents on the surface of polyurethane coatings.

Residual organic solvents have a great impact on the physical and mental health of equipment operators in industry and agriculture. Laser waterless cleaning technology of residual organic solvents on the surface of polyurethane coatings has great application prospects and is a good way to tackle the pollution problem. In this paper, the evolutionary behavior of a laser waterless cleaning mechanism and substrate surface state is analyzed. The influence law of laser energy density and scanning speed on the residual solvent cleaning effect was investigated. The optimal laser cleaning parameters were obtained by comprehensive evaluation of the substrate surface cleaning effect and microscopic morphology. The peak of solvent characteristics before and after laser cleaning was detected by Raman spectroscopy. The results demonstrated that the laser cleaning effect was better with the increase of energy density or the decrease of scanning speed in the substrate damage range, and the best laser cleaning parameters were laser energy density of 0.24J/c m 2 and scanning speed of 500 mm/s. A significant reduction of the peak of Raman spectroscopy was found, reflecting the excellent effect of laser waterless cleaning of residual organic solvents.

Metformin Ameliorates 2.856 GHz Microwave- Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis.

The reproductive system has been increasingly implicated as a sensitive target of microwave radiation. Oxidative stress plays a critical role in microwave radiation -induced reproductive damage, though precise mechanisms are obscure. Metformin, a widely used antidiabetic drug, has emerged as an efficient antioxidant against a variety of oxidative injuries. In the present study, we hypothesized that metformin can function as an antioxidant and protect the reproductive system from microwave radiation. To test this hypothesis, rats were exposed to 2.856 GHz microwave radiation for 6 weeks to simulate real-life exposure to high-frequency microwave radiation. Our results showed that exposure to 2.856 GHz microwave radiation elicited serum hormone disorder, decreased sperm motility, and depleted sperm energy, and it induced abnormalities of testicular structure as well as mitochondrial impairment. Metformin was found to effectively protect the reproductive system against structural and functional impairments caused by microwave radiation. In particular, metformin can ameliorate microwave-radiation-induced oxidative injury and mitigate apoptosis in the testis, as determined by glutathione/-oxidized glutathione (GSH/GSSG), lipid peroxidation, and protein expression of heme oxygenase-1 (HO-1). These findings demonstrated that exposure to 2.856 GHz microwave radiation induces obvious structural and functional impairments of the male reproductive system, and suggested that metformin can function as a promising antioxidant to inhibit microwave-radiation-induced harmful effects by inhibiting oxidative stress and apoptosis.

Effect of flocculant dosage on the settling properties and underflow concentration of thickener for flocculated tailing suspensions.

Flocculation is important in the thickening process to improve the underflow concentration in thickeners for tailing suspensions. Traditional zone settling velocity (ZSV) functions ignore the effect of flocculant dosage on the ZSV and the thickening behavior of thickeners. To investigate the effect of flocculant dosage on the settling flux function, a series of batch settling tests were conducted at various flocculant dosages for unclassified and fine tailings. The correlation among flocculant dosage, solid fraction, and parameters in the ZSV function was revealed. Moreover, a simulation of continuous thickening based on the ZSV function was performed. Results indicated that flocculation influenced settling velocity and floc density. With an increased flocculant dosage, the settling velocity of floc increased, resulting in increased underflow concentration. Conversely, floc density decreased due to a stronger particle-particle interaction, leading to a decreased underflow concentration.

NRF2/PGC-1α-mediated mitochondrial biogenesis contributes to T-2 toxin-induced toxicity in human neuroblastoma SH-SY5Y cells.

The T-2 toxin is a highly toxic trichothecene mycotoxin that would cause serious toxicity in humans and animals. Recent studies suggest that the central nervous system (CNS) is susceptible to T-2 toxin, which can easily cross the blood-brain barrier, accumulate in brain tissues, and cause neurotoxicity. The growing evidence indicates that oxidative damage and mitochondrial dysfunction play a critical role in T-2 toxin-induced neurotoxicity, but the mechanisms are still poorly understood. Our present study showed that T-2 toxin decreased cell viability and increased lactate dehydrogenase leakage in human neuroblastoma SH-SY5Y cells in a concentration- and time-dependent manner. T-2 toxin elicited prominent oxidative stress and mitochondrial dysfunction, as evidenced by the promotion of cellular reactive oxygen species generation, disruption of the mitochondrial membrane potential, depletion of glutathione and reduction of the cellular ATP content. T-2 toxin impaired mitochondrial biogenesis, including decreased mitochondrial DNA copy number and affected the nuclear factor erythroid 2 related factor 2 (NRF2) / peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) pathway by upregulating NRF2 mRNA and protein expression while inhibiting the expression of PGC-1α, nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM). NRF2 knockdown was found to significantly exacerbate T-2 toxin-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction, as well as aggravate mitochondrial biogenesis impairment. NRF2 knockdown compromised T-2 toxin-induced upregulation of NRF2, but augmented the inhibition of PGC-1α, NRF1, and TFAM by T-2 toxin. Taken together, these findings suggest that T-2 toxin-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells, at least in part by, NRF2/PGC-1α pathway-mediated mitochondrial biogenesis.

Synergistic effects of Rapamycin and Fluorouracil to treat a gastric tumor in a PTEN conditional deletion mouse model.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) in PI3K/Akt/mTOR pathway is essential in inhibiting tumor growth and metastasis. However, whether the mutation of PTEN gene could induce tumorigenesis and impact the treatment of gastric cancer is still unclear. The purpose of the study was to investigate the combined treatment of gastric tumorigenesis using Rapamycin and Fluorouracil (5-Fu) through interfering with the Akt/mTOR pathway in a mouse model with PTEN conditional deletion. Three groups of mice were exposed for 5 days to Rapamycin and 5-Fu separately and together. The gene expression of the Akt/mTOR pathway, the protein expression of caspase-3 and p-Akt, p-S6K and p-4EBP1, and the pathological changes in stomachs were analyzed. Our study demonstrates that the conditional PTEN deletion in the cells of glandular stomach induces hyperplastic gastric tumors in mice. The combined Rapamycin administration with 5-Fu resulted in better outcomes than their separate administration for the treatment of gastric cancer by inhibiting the mTOR signal pathway. Our study indicates that Rapamycin has a synergistic interaction with chemotherapeutic 5-Fu, and demonstrates a potential therapeutic combination treatment on glandular stomach tumor with PTEN functional absence or aberrantly activated Akt/mTOR pathway. It provides important insights into the inhibition of the Akt/mTOR pathway in gastric cancer clinical therapy.

Integration of in vitro data from three dimensionally cultured HepaRG cells and physiologically based pharmacokinetic modeling for assessment of acetaminophen hepatotoxicity.

Selection of appropriate fit-for-purpose in vitro and in silico models is critical for non-animal safety assessment of chemical-induced hepatoxicity. The present study evaluated the feasibility of integrating in vitro data from three-dimensionally (3D)-cultured HepaRG cells and physiologically based pharmacokinetic (PBPK) modeling to predict chemical-induced liver toxicity. A 3D organoid culture system was established using an ultralow attachment method. HepaRG cells cultured in a two-dimensional (2D) monolayer and under 3D conditions were exposed to acetaminophen (APAP) at concentrations of 0.16-20 mM. The results showed that the viability of both 3D- and 2D cultured cells was significantly decreased by APAP in a concentration-dependent manner. Furthermore, 3D cultures were more sensitive to APAP-induced mitochondrial damage than 2D cultures were, based on measurements of mitochondrial superoxide accumulation and mitochondrial membrane potential loss. PBPK simulations using nominal in vitro concentrations showed that the APAP concentration eliciting mitochondrial damage was closer to the predicted peak liver concentration in humans in 3D cultures than it was in 2D cultures. In summary, our results suggest that combining in vitro data from 3D HepaRG cultures and PBPK modeling provides a promising tool for assessment of liver injury.

Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway.

Atorvastatin (ATO) is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor widely used to treat hypercholesterolemia. However, clinical application is limited by potential hepatotoxicity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a master regulator of cellular antioxidants, and oxidative stress is implicated in statin-induced liver injury. This study investigated mechanisms of ATO-induced hepatotoxicity and potential mitigation by Nrf2 signaling. ATO reduced Nrf2 and antioxidant enzyme superoxide dismutase-2 (SOD2) expression in human hepatocarcinoma HepG2 cells. ATO also induced concentration-dependent HepG2 cell toxicity, reactive oxygen species (ROS) accumulation, and mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential (MMP) and cellular adenosine triphosphate (ATP). Further, ATO induced mitochondria-dependent apoptosis as indicated by increased Bax/Bcl-2 ratio, cleaved caspase-3, mitochondrial cytochrome c release and Annexin V-fluorescein isothiocyanate/propidium iodide staining. Tert-butylhydroquinone enhanced Nrf2 and SOD2 expression, and partially reversed ATO-induced cytotoxicity, ROS accumulation, MMP reduction, ATP depletion and mitochondria-dependent apoptosis. In conclusion, the present study demonstrates that ATO induces mitochondrial dysfunction and cell apoptosis in HepG2 cells, at least in part, via inhibition of the Nrf2 pathway. Nrf2 pathway activation is a potential prevention for ATO-induced liver injury.

Constructing Ultrahigh-Capacity Zinc-Nickel-Cobalt Oxide@Ni(OH)2 Core-Shell Nanowire Arrays for High-Performance Coaxial Fiber-Shaped Asymmetric Supercapacitors.

Increased efforts have recently been devoted to developing high-energy-density flexible supercapacitors for their practical applications in portable and wearable electronics. Although high operating voltages have been achieved in fiber-shaped asymmetric supercapacitors (FASCs), low specific capacitance still restricts the further enhancement of their energy density. This article specifies a facile and cost-effective method to directly grow three-dimensionally well-aligned zinc-nickel-cobalt oxide (ZNCO)@Ni(OH)2 nanowire arrays (NWAs) on a carbon nanotube fiber (CNTF) with an ultrahigh specific capacitance of 2847.5 F/cm3 (10.678 F/cm2) at a current density of 1 mA/cm2, These levels are approximately five times higher than those of ZNCO NWAs/CNTF electrodes (2.10 F/cm2) and four times higher than Ni(OH)2/CNTF electrodes (2.55 F/cm2). Benefiting from their unique features, we successfully fabricated a prototype coaxial FASC (CFASC) with a maximum operating voltage of 1.6 V, which was assembled by adopting ZNCO@Ni(OH)2 NWAs/CNTF as the core electrode and a thin layer of carbon coated vanadium nitride (VN@C) NWAs on a carbon nanotube strip (CNTS) as the outer electrode with KOH poly(vinyl alcohol) (PVA) as the gel electrolyte. A high specific capacitance of 94.67 F/cm3 (573.75 mF/cm2) and an exceptional energy density of 33.66 mWh/cm3 (204.02 µWh/cm2) were achieved for our CFASC device, which represent the highest levels of fiber-shaped supercapacitors to date. More importantly, the fiber-shaped ZnO-based photodetector is powered by the integrated CFASC, and it demonstrates excellent sensitivity in detecting UV light. Thus, this work paves the way to the construction of ultrahigh-capacity electrode materials for next-generation wearable energy-storage devices.

International Harmonization and Cooperation in the Validation of Alternative Methods.

The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

Emerging Amorphous to Crystalline Conversion Chemistry in Ca-Doped VO2 Cathodes for High-Capacity and Long-Term Wearable Aqueous Zinc-Ion Batteries.

Amorphous transition metal oxides have attracted significant attention in energy storage devices owing to their potentially desirable electrochemical properties caused by abundant unsaturated dangling bonds. However, the amorphization further amplifies the shortcoming of the poor intrinsic electronic conductivity of the metal oxides, resulting in unsatisfying rate capability and power density. Herein, freestanding amorphous Ca-doped V2 O5 (a-Ca-V2 O5 ) cathodes are successfully prepared via in situ electrochemical oxidation of Ca-doped VO2 nanoarrays for wearable aqueous zinc-ion batteries. The doping of Ca and construction of freestanding structure effectively uncover the potential of amorphous V2 O5 , which can make full use of the abundant active sites for high volumetric capacity and simultaneously achieve fast reaction kinetics for excellent rate performance. More importantly, the introduction of Ca can notably reduce the formation energy of VO2 according to theoretical calculation results and realizes amorphous to crystalline reversible conversion chemistry in the charge/discharge procedure, thereby facilitating the reversible capacity of the newly developed a-Ca-V2 O5 . This work provides an innovative design strategy to construct high-rate capacity amorphous metal oxides as freestanding electrodes for low-cost and high-safe wearable energy-storage technology.

Long-Lifespan Fibrous Aqueous Ni//Bi Battery Enabled by Bi2O3-Bi2S3 Hierarchical Heterostructures.

Bismuth oxide (Bi2O3) materials are considered as great promising anodes for aqueous batteries on account of the high capacity as well as wide potential plateau. Nevertheless, the low conductivity and severe volumetric change of Bi2O3 in the course of cycling are the main limiting factors for their application in energy-storage systems. Herein, we propose and design unique hierarchical heterostructures constructed by Bi2O3 and Bi2S3 nanosheets (NSs) manufactured immediately on the surface of carbon nanotube fibers (CNTFs). The Bi2O3-Bi2S3 (BO-BS) exhibits enhanced conductivity and increased stability in comparison with pure Bi2O3 and Bi2S3. The BO-BS NSs/CNTF electrode indicates exceptional rate capability and cycling stability, while creating a high reversible capacity of 0.68 mAh cm-2 at 4 mA cm-2, as anticipated. Additionally, the quasi-solid-state fibrous aqueous Ni//Bi battery that was built with the BO-BS NSs/CNTF anode delivers an exceptional cycling stability of 52.7% capacity retention after 4000 cycles at 80 mA cm-2, an ultrahigh capacity of 0.35 mAh cm-2 at 4 mA cm-2, and a high energy density of 340.1 mWh cm-3 at 880 mW cm-3. This work demonstrates the potential of constructing hierarchical heterostructures of bismuth-based materials for high-performance aqueous Ni//Bi batteries and other energy-storage devices.

Standard: human intestine-on-a-chip.

Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. "Organs-on-chips: Intestine" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.

Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes. Moreover, the binding and releasing of the guests in the complexes could be controlled by potassium ions.

T-2 toxin induces cardiotoxicity by activating ferroptosis and inhibiting heme oxygenase-1.

T-2 toxin, a natural secondary sesquiterpenoid metabolite produced by numerous strains of Fusarium fungi, is prevalent in both contaminated food and the environment. T-2 toxin is known to be highly toxic to the cardiovascular system, but the precise mechanisms that lead to T-2 toxin-induced cardiotoxicity are not yet fully understood. Recent findings indicate that ferroptosis is a pivotal factor in cardiovascular damage and exhibits a strong correlation with the detrimental impacts of T-2 toxin. The present study was designed to examine the involvement of ferroptosis in T-2 toxin-induced cardiac injury. Male mice and human cardiomyocytes were subjected to T-2 toxin for 24 h to induce acute cardiotoxicity for in vivo and in vitro studies, respectively. Our results demonstrated that T-2 toxin increased reactive oxygen species production, malondialdehyde, and decreased glutathione/oxidized glutathione and adenosine triphosphate levels. Furthermore, T-2 toxin was observed to activate ferroptosis, as evidenced by an increase in iron (Fe2+) concentration and upregulation of prostaglandin endoperoxide synthase 2, downregulation of glutathione peroxidase 4 and ferritin heavy chain 1, as well as ferroptotic morphological alterations. Inhibition of ferroptosis by Liproxstatin-1 reversed T-2 toxin-induced cardiac injury. Additionally, the downregulation of heme oxgenase-1 (HO-1) expression by T-2 toxin exacerbates ferroptosis and oxidative damage, which can be further aggravated by HO-1 inhibition with Sn-protoporphyrin. These findings provide novel insights into the mechanism of T-2 toxin-induced cardiotoxicity and suggest that targeting ferroptosis and HO-1 may represent a promising cardioprotective strategy against T-2 toxin.

Free-standing conductive nickel metal-organic framework nanowires as bifunctional electrodes for wearable pressure sensors and Ni-Zn batteries.

Free-standing metal-organic frameworks (MOFs) with controllable structure and good stability are emerging as promising materials for applications in flexible pressure sensors and energy-storage devices. However, the inherent low electrical conductivity of MOF-based materials requires complex preparation processes that involve high-temperature carbonization. This work presents a simple method to grow conductive nickel MOF nanowire arrays on carbon cloth (Ni-CAT@CC) and use Ni-CAT@CC as the functional electrodes for flexible piezoresistive sensor. The resulting sensor is able to monitor human activity, including elbow bending, knee bending, and wrist bending. Besides, the soft-packaged aqueous Ni-Zn battery is assembled with Ni-CAT@CC, a piece of glass microfiber filters, and Zn foil acting as cathode, separator, and anode, respectively. The Ni-Zn battery can be used as a power source for finger pressure monitoring. This work demonstrates free-standing MOF-based nanowires as bifunctional fabric electrodes for wearable electronics.

The phosphoproteome is a first responder in tiered cellular adaptation to chemical stress followed by proteomics and transcriptomics alteration.

Next-generation risk assessment (NGRA) for environmental chemicals involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained from in vitro assays. Among existing NAMs, the omic-based technologies are of particular importance based on the premise that any apical endpoint change indicative of impaired health must be underpinned by some alterations at the omics level, such as transcriptome, proteome, metabolome, epigenome and genome. Transcriptomic assay plays a leading role in providing relatively conservative PoDs compared with apical endpoints. However, it is unclear whether and how parameters measured with other omics techniques predict the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we conducted multi-omics studies of transcriptomics, proteomics and phosphoproteomics on two prototype compounds, coumarin and 2,4-dichlorophenoxyacetic acid (2,4-D), with multiple chemical concentrations and time points, to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2. We demonstrated that, phosphoproteomics alterations occur not only earlier in time, but also more sensitive to lower concentrations than proteomics and transcriptomics when the HepG2 cells were exposed to various chemical treatments. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to initiate. Therefore, it is proximal to the very early effects induced by chemical exposure. We concluded that phosphoproteomics can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.

T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through reactive oxygen species-mediated mitochondrial pathway.

T-2 toxin, a member of the trichothecene mycotoxin family produced by the Fusarium fungi, has been shown to exert a variety of toxic effects on multiple targets in vivo. However, the embryonic toxicity of T-2 toxin in vitro remains unclear. In the present study, two permanent cell lines, embryonic stem cells (ES cells D3) and fibroblast 3T3 cells, were used to evaluate T-2 toxin toxicity. Differentiated mouse ES cells were cultivated as embryoid bodies along with T-2 toxin at different concentrations (0.5, 1, and 2 ng/ml) for 24 h. The increases in cellular reactive oxygen species (ROS), lipid and DNA oxidative damage, and loss of mitochondrial transmembrane potential were observed at 1 and 2 ng/ml concentrations. Flow cytometry showed that T-2 toxin induced cell cycle arrest and apoptosis. Furthermore, T-2 toxin opened the mitochondrial permeability transition pore, caused the release of cytochrome c from mitochondria and induced the upregulation of p53, caspase-9, caspase-3 expression and increased the ratio of Bax/Bcl-2. However, T-2 toxin-induced oxidative damage and apoptosis in differentiated ES cells decreased significantly in the presence of the antioxidant Trolox. Taken together, these results demonstrate that T-2 toxin induces oxidative stress and apoptosis in differentiated murine ES cells, and ROS-mediated mitochondrial pathway plays an important role in T-2 toxin induced apoptosis.

Synthesis of triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties and its complexation with paraquat derivatives: Li(+)-ion-controlled binding and release of the guests in the complexes.

A new triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties was synthesized and shown to form 1:1 complexes with paraquat derivatives in solution, in which the guests all thread the central cavity of the host. However, it was interestingly found that, depending on the paraquat derivatives with different functional groups, the host can form stable 1:1 or 1:2 complexes in different complexation modes in the solid state, which is significantly different from those of the macrotricyclic host containing two dibenzo-[24]-crown-8 moieties. The formation of the complexes was also proved by the ESI MS and electrochemical experiments. Moreover, it was found that the binding and release of the guests in the complexes could be easily controlled by the addition and removal of lithium ions.