MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson's disease.

Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl-/-) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl-/- mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl-/- mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

Formation characteristics and acute toxicity assessment of THMs and HAcAms from DOM and its different fractions in source water during chlorination and chloramination.

The formation characteristics of trihalomethanes (THMs) and haloacetamides (HAcAms) from dissolved organic matter and its fractions were investigated during chlorine-based disinfection processes. The relationships between water quality parameters, fluorescence parameters, and the formation levels of THMs and HAcAms were analyzed. The fractions contributing most to the acute toxicity were identified. The trichloromethane (TCM) generation level (72 h) generally followed the order of Cl2 > NH2Cl > NHCl2 process. The NHCl2 process was superior to the NH2Cl process in controlling TCM formation. Hydrophobic acidic substance (HOA), hydrophobic neutral substance (HON), and hydrophilic substance (HIS) were identified as primary precursors of 2,2-dichloroacetamide and trichloroacetamide during chlorination and chloramination. The formation of TCM mainly resulted from HOA, HON and HIS fractions relatively uniformly, while HOA and HIS fractions contributed more to the formation of bromodichloromethane and dibromomonochloromethane. UV254 could be used as an alternative indicator for the amount of ΣTHMs formed during chlorination and chloramination processes. Dissolved organic nitrogen was a potential precursor of 2,2-dichloroacetamide during chlorination process. The fractions with the highest potential acute toxicity after the chlorination were water-dependent.

[Seasonal change of habitat selection of Hydropotes inermis in Yancheng coastal wetlands, China]. / ç›åŸŽæ»¨æµ·æ¹¿åœ°çæ –æ¯åœ°é€‰æ‹©çš„å­£èŠ‚å˜åŒ–.

Yancheng coastal wetlands are one of the main habitats and breeding grounds of wild Chinese water deer (Hydropotes inermis). Based on GPS-GSM tracking data, we used the habitat selection index and MaxEnt model to simulate and analyze the distribution of suitable habitat of H. inermis in different seasons as well as the main influencing factors. The results showed that H. inermis mainly used reed marshes, with the usage rate in spring-summer and autumn-winter being 52.7% and 62.8%, respectively. The area under receiver operating characteristic curve value simulated by MaxEnt model in different seasons was 0.873 and 0.944, which showed high prediction accu-racy. In spring and summer, the sub-suitable and most suitable habitats were mainly reed marshes, farmland, and ponds. In autumn and winter, the main habitat types were reed marshes and ponds, with an area equivalent to only 5.7% and 8.5% of that in spring and summer. Distance to reeds, distance to Spartina alterniflora, habitat types, distance to water and distance residential area were the main environmental variables affecting the distribution of H. inermis in spring and summer. The above five variables and vegetation height were the main environmental variables affecting the distribution of H. inermis in autumn and winter. This study would provide an important reference for the conservation of Chinese water deer and the fine management of their habitats in Yancheng coastal wetlands.

p Components of Cluster-Lag Consensus for Second-Order Multiagent Systems With Adaptive Controller on Cooperative-Competitive Networks.

The consensus tracking problem means that a group of followers tracks the desired trajectory with local communication. In this article, partial components of cluster consensus have been considered. In this scenario, the p components of the followers in different clusters track the leader at different lag times, while p components of each agent in the same cluster reach a consensus, which is called p components of cluster-lag (PCCL) consensus. By using a seminorm ||xi||2,p and a Lyapunov-Krasovskii functional, PCCL consensus for second-order multiagent systems with homogeneous nonlinear systems on cooperative-competitive networks has been considered. For the case that the communication network graph is undirected, a decentralized adaptive controller, which is based on the exchanged neighbors' information from the same cluster, is designed such that all the agents reach PCCL consensus. For the directed graph case, an adaptive protocol based on the intracoupling strength is constructed for each cluster to achieve PCCL consensus. Finally, two simulation examples are illustrated to show the effectiveness of the proposed control protocols.

High-performance reductive decomposition of trichloroacetamide by the vacuum-ultraviolet/sulfite process: Kinetics, mechanism and combined toxicity risk.

Trichloroacetamide (TCAcAm) is among of the nitrogenous disinfection by-products (N-DBPs) with high cytotoxicity and genotoxicity, which is usually detected at low concentration (µg/L) in drinking water. In this study, advanced reduction process (ARP) based on vacuum ultraviolet (VUV) was employed to eliminate TCAcAm. Compared with VUV, VUV/sulfide, and VUV/ferrous iron processes, VUV/sulfite process demonstrated excellent performance for TCAcAm decomposition, the higher removal of TCAcAm could be achieved by VUV/sulfite process (85.6 %) than VUV direct photolysis (13.5 %) due to the production of a great number of reactive species. The degradation of TCAcAm followed the pseudo-first-order kinetics well in VUV/sulfite process, and the pseudo-first-order rate constant (kobs) increased with increasing sulfite concentration. Reactive species quenching experiments demonstrated that eaq-, SO3·- and H· were involved in the degradation of TCAcAm. The in situ generated eaq-, SO3·- and HO· via VUV/sulfite process were identified by electron paramagnetic resonance (EPR), and the eaq- was proved to be the dominated species (relative contribution: 83.5 %) for TCAcAm decomposition. The second-order rate constant of TCAcAm with eaq- was determined to be 2.41 × 1010 M-1 s-1 for the first time based on competitive kinetic method. The complete TCAcAm degradation could be achieved at pH > 8.3, while TCAcAm degradation efficiency decreased to 11.9 % at pH 5.8. TCAcAm decay could be divided into two stages: rapid growth (sulfite dosage: 0.25-1.0 mM) and slow growth (sulfite dosage: 1.0-4.0 mM). The yield of eaq- was controlled by sulfite dosage, and the predict yield of eaq- increased from 3.69 × 10-14 to 2.58 × 10-12 M with increasing the sulfite dosage from 0.25 to 4.0 mM by Kintecus 6.80, which resulted in an increase in TCAcAm removal. Meanwhile, the presence of dissolved oxygen (DO), chloride (Cl-), bicarbonate (HCO3-) and humic acid (HA) posed negative influence on TCAcAm decomposition to various degrees. Dichloroacetamide (DCAcAm), trichloroacetic acid (TCAA), dichloroacetic acid (DCAA) and Cl- were identified as intermediate products, indicated that reductive dechlorination and hydrolysis coexisted during the degradation of TCAcAm in VUV/sulfite process.

Chronic effects of microcystin-LR at environmental relevant concentrations on photosynthesis of Typha angustifolia Linn.

Understanding the growth and development of aquatic plants in eutrophic water is of great significance for the selection of potential candidate plant for use in the phytoremediation of eutrophic aquatic ecosystems. The present study aimed to investigate the chronic effects of microcystin-LR (MC-LR) on photosynthesis in the leaves of Typha angustifolia Linn. Photosynthetic activity was stimulated in the leaves following exposure to 4.6 µg L-1 MC-LR for six weeks based on the enhancement of Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) activity and net photosynthetic rate (PN). However, PN decreased significantly after exposure to 49.1 or 98.3 µg L-1 MC-LR, via non-stomatal limitation by reducing the chlorophyll a and b contents and Rubisco activity. In addition, glycolate oxidase (GO) and serine:glyoxylate aminotransferase (SGAT) activities decreased significantly, indicating that the photorespiration pathway was affected adversely. The intercellular carbon dioxide (Ci) concentration decreased significantly following exposure to 98.3 µg L-1 MC-LR, accompanied with decreases in PN and stomatal conductivity (gs), indicating that stomatal limitation on the photosynthesis system in T. angustifolia L. was observed after exposure to 98.3 µg L-1 MC-LR. Under long-term exposure to MC-LR (49.1-98.3 µg L-1), oxidation stress was severe in the aquatic plant, and non-stomatal limitation or stomatal limitation effects on the photosynthesis system were obvious, resulting in decreases in photosynthesis rates.

Comparison of acetaminophen degradation in UV-LED-based advance oxidation processes: Reaction kinetics, radicals contribution, degradation pathways and acute toxicity assessment.

Ultraviolet light emitting diode (UV-LED)-based advanced oxidation processes (AOPs) including UV-LED/chloramine (UV-LED/NH2Cl), UV-LED/hydrogen peroxide (UV-LED/H2O2) and UV-LED/persulfate (UV-LED/PS), were adopted for acetaminophen (AAP) removal. Results showed that AAP could be effectively degraded by the hybrid processes compared to solely using with UV irradiation and oxidants. The AAP degradation in the three UV-LED-based AOPs were in the order of UV-LED/PS > UV-LED/H2O2 > UV-LED/NH2Cl and followed a pseudo-first-order kinetics. The degradation rate constant (kobs) increased with increasing oxidant dosage, whereas overdosing lowered the AAP degradation. The second-order rate constants of HO, SO4-, and Cl with AAP were calculated as 5.15 × 109, 7.66 × 109 and 1.08 × 1010 M-1 s-1, respectively. Under neutral conditions, the contributions of UV-LED, HO, and Cl to AAP degradation were 4.21%, 60.15% and 35.64% in the UV-LED/NH2Cl system, whereas the respective contributions of UV-LED, HO and SO4- to AAP degradation were 2.09%, 22.84% and 75.07% in UV-LED/PS system, respectively. Meanwhile, the corresponding contributions of the involved reactive species were found to be pH-dependence. The natural organic materials (NOM) inhibited the AAP degradation, and the presence of Cl-, HCO3-, and NO3- had different effects on AAP degradation in the three hybrid processes. The AAP degradation was significantly inhibited in the three UV-LED-based AOPs in real water. In addition, the intermediate products were also identified, and possible degradation pathways were proposed in the three UV-LED-based AOPs. The acute toxicity bioassay using bacterium Vibrio fischeri suggested that the UV-LED/PS process was more effective than the UV-LED/H2O2 and UV-LED/NH2Cl processes in reducing the acute toxicity of the reacted AAP solution. Among the three UV-LED-based AOPs, the UV-LED/PS was found to be the most efficient process for AAP degradation.

Nitrogen Metabolism in Acorus calamus L. Leaves Induced Changes in Response to Microcystin-LR at Environmentally Relevant Concentrations.

Acorus calamus L., a semiaquatic plant with a high capacity to remove nitrogen and phosphorus from polluted water, is a potential candidate plant for use in the restoration of eutrophic aquatic ecosystems. However, it is not clear how microcystins (MCs), commonly found in eutrophic water, influence plant growth since the effects of MCs are likely to be dose and species dependent. The present study aimed to investigate the regulation of nitrogen metabolism, a key metabolic process related to plant growth, in the leaves of A. calamus L. exposed to microcystin-leucine-arginine (MC-LR) (1.0-29.8 µg/L). Nitrate (NO3-) uptake, assimilation and transformation was stimulated in the leaves of A. calamus L. when exposed to 1.0 µg/L MC-LR through the elevation of nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT), glutamic-pyruvic transaminase (GPT), and glutamic-oxaloacetic transaminase (GOT) activity. Conversely, MC-LR inhibited nitrogen metabolism by decreasing NO3- uptake and the activities of enzymes related to nitrogen metabolism following exposure to MC-LR (9.9-29.8 µg/L) for 30 days, while, ammonium nitrogen (NH4+) content and glutamate dehydrogenase (GDH) activity increased significantly (p < 0.05, LSD test), when compared with the control group. Chronic exposure to MC-LR (9.9-29.8 µg/L) negatively influenced nitrogen metabolism in A. calamus L. leaves, which suggested that it may not be a suitable candidate species for use in the restoration of eutrophic aquatic ecosystems containing MC-LR at concentrations ≥ 9.9 µg/L.

Subcellular distribution, chemical forms, and physiological response to cadmium stress in Hydrilla verticillata.

This study investigated the subcellular distribution and chemical forms of cadmium (Cd) in Hydrilla verticillata and the physiological mechanism underlying H. verticillata responses to Cd stress. Hydrilla verticillata was grown in a hydroponic system and was treated with various Cd concentrations (0, 10, 50, 100, 125, and 150 µM) for 7 days. Cadmium analysis of the leaves at the subcellular level showed that Cd was mainly stored in the soluble fraction (77.98-83.62%) and in smaller quantities in the cell wall fraction (11.99-17.30%) and the cell organelles (4.30-4.88%). The Cd taken up by H. verticillata was in different chemical forms. In the leaves and stems, the Cd was mostly extracted using 1 M NaCl and smaller amounts of Cd were extracted using 2% acetic acid. The malondialdehyde content significantly increased at all Cd concentrations, which indicated oxidative stress. The superoxide dismutase, guaiacol peroxidase, and catalase activities were enhanced. The proline, ascorbate, and glutathione contents increased at lower Cd concentrations, but decreased consistently as the Cd concentration rose. These results suggest that H. verticillata can be successfully used in the phytoremediation of Cd-contaminated water.

Functional Silencing of HSD17B2 in Prostate Cancer Promotes Disease Progression.

PURPOSE: Steroidogenic enzymes are essential for prostate cancer development. Enzymes inactivating potent androgens were not investigated thoroughly, which leads to limited interference strategies for prostate cancer therapy. Here we characterized the clinical relevance, significance, and regulation mechanism of enzyme HSD17B2 in prostate cancer development. EXPERIMENTAL DESIGN: HSD17B2 expression was detected with patient specimens and prostate cancer cell lines. Function of HSD17B2 in steroidogenesis, androgen receptor (AR) signaling, and tumor growth was investigated with prostate cancer cell lines and a xenograft model. DNA methylation and mRNA alternative splicing were investigated to unveil the mechanisms of HSD17B2 regulation. RESULTS: HSD17B2 expression was reduced as prostate cancer progressed. 17ßHSD2 decreased potent androgen production by converting testosterone (T) or dihydrotestosterone (DHT) to each of their upstream precursors. HSD17B2 overexpression suppressed androgen-induced cell proliferation and xenograft growth. Multiple mechanisms were involved in HSD17B2 functional silencing including DNA methylation and mRNA alternative splicing. DNA methylation decreased the HSD17B2 mRNA level. Two new catalytic-deficient isoforms, generated by alternative splicing, bound to wild-type 17ßHSD2 and promoted its degradation. Splicing factors SRSF1 and SRSF5 participated in the generation of new isoforms. CONCLUSIONS: Our findings provide evidence of the clinical relevance, significance, and regulation of HSD17B2 in prostate cancer progression, which might provide new strategies for clinical management by targeting the functional silencing mechanisms of HSD17B2.See related commentary by Mostaghel, p. 1139.

Degradation of triclosan by chlorine dioxide: Reaction mechanism,2,4-dichlorophenol accumulation and toxicity evaluation.

The mechanism and toxicity of TCS degradation by ClO2 was investigated. Intermediate products during the oxidation process were identified by GC/MS and LC/MS. A microtox bioassay and a SOS/umu assay were employed to evaluate the acute toxicity and genotoxicity of the resulting solutions during the chlorination process. The results showed that the reaction between TCS and ClO2 was of second-order overall. The pseudo first-order rate constants (kobs) exhibited significant dependence on solution pH and chlorine dioxide concentration, with the apparent second-order rate constant, kapp, being 7.07 × 104 M-1s-1 in the pH range of 6.80-7.02. TCS decomposition was accompanied by the accumulation of 2,4-dichlorophenol (2,4-DCP), and the maximum molar yield ratios of 2,4-DCP/TCS were in the range of 31.71%-35.43%. The major intermediates identified were 2,7/2,8-dichlorodibenzop-dioxin (2,7/2.8-Cl2DD), 2,4-DCP, 2,4,6-trichlorophenol (2,4,6-TCP), tetraclosan and pentaclosan. The proposed mechanism for TCS oxidation involved the cleavage of the ether link in TCS, chlorination of the phenolic ring and ring closure of a single TCS molecule. The transformation and degradation of TCS led to reduction of the acute toxicity and genotoxicity. However, irregular fluctuations in the toxicity changes indicated that the oxidation of TCS was not a simultaneous detoxification process.

Degradation behavior of triclosan by co-exposure to chlorine dioxide and UV irradiation: influencing factors and toxicity changes.

This study investigated the transformation of triclosan (TCS) following co-exposure to UV irradiation and ClO2. Special attention was given to understand the influencing of water quality parameters and toxicity changes during the co-exposure process. The results show that the co-exposure process prompted TCS elimination quickly and effectively, with more than 99% of TCS degraded under the experimental conditions. The molar yield ratios of 2,4-dichlorophenol/TCS (2,4-DCP/TCS) were calculated to be 35.81-74.49%; however, the by-product of 2,8-dichlorodibenzop-dioxin (2,8-Cl2DD) was not detected. The TCS degradation was sensitive to ClO2 dosage, pH, H2O2, and natural organic matter (NOM), but not to the carbonate (CO32-) concentration. Neutral and slightly alkaline condition were favorable to TCS elimination. The TCS removal rate increased from 85.33 to 99.75% when the ClO2 concentration increased from 0.25 to 1.5 mg L-1. TCS degradation can be promoted at low NOM level (1, 3, and 5 mg L-1), whereas was inhibited at high NOM concentrations of 7 and 9 mg L-1. While adding H2O2, the degradation rate of TCS increased with increasing H2O2 concentration from 1 to 3 mg L-1; however, too low or overdosed H2O2 (0.5 and 5 mg L-1) hindered TCS degradation. Based on the results of a microtox bioassay, the toxicity did not change following the co-exposure process.

[Efficiency and Kinetics of Triclosan Degradation in Aqueous Solution by UV/Sodium Persulfate].

UV activated sodium persulfate was employed to remove triclosan (TCS) in aqueous solution. The effects of several factors such as UV wavelength,UV254 intensity,sodium persulfate dosage,pH value,and HA on TCS degradation were investigated. The second-order rate constants of free radicals (·OH, SO4·-) reacting with TCS and their contributions to TCS removal were determined,respectively. The dominant free radical was also identified. Furthermore, the TCS degradation efficiency in natural water by UV254/SPS and UV254/H2O2 was compared. Finally,the possible pathway and intermediate products of TCS degradation were analyzed with GC/MS. The results indicated that UV254 activated sodium persulfate could effectively remove TCS. The removal rate of TCS could reach 98.15% within 100s under the conditions of UV wavelength of 254 nm,UV intensity of 11.5µW·cm-2,sodium persulfate dosage of 1mmol·L-1,and TCS initial concentration of 275 µg·L-1. TCS degradation followed the pseudo-first-order kinetic model and the pseudo-first-order rate constant was determined to be 0.0392 s-1. Pseudo-first-order rate constant for TCS degradation increased with the increase of UV254 intensity(I)and sodium persulfate dosage within experiment ranges. The effect of UV wavelength on TCS removal was not notable. Neutral condition was detrimental to TCS degradation. TCS removal was inhibited in the presence of HA. The reaction rate constants for·OH and SO4·- reacting with TCS were 7.62×109 L·mol-1·s-1 and 9.86×109 L·mol-1·s-1,respectively. SO4·- was the dominant free radical and its contribution rate to TCS removal was 97.63% in UV254/SPS system. The K value of UV254/SPS was 4.13 times higher than that of UV254/H2O2 process,which demonstrated that UV254/SPS process could remove TCS more effectively than UV254/H2O2. The main intermediate products found were 2,4-DCP and phenol in the degradation process of TCS in Milli-Q water by UV254/SPS.

The Effects of Occupational Exposure of Carbon Disulfide on Sexual Hormones and Semen Quality of Male Workers From a Chemical Fiber Factory.

OBJECTIVE: This study is aimed to analyze the relationship between occupational CS2 exposure and reproductive impairments. METHODS: Seventy-six CS2-exposed (9.73 ±â€Š2.76 mg/m(3)) male workers and 94 unexposed workers were selected for study. Worker demographics were assessed with a customized questionnaire. Sexual hormones and sperm-related parameters were measured by biochemical or morphological analysis. RESULTS: The CS2-exposed workers had significantly higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and lower levels of testosterone (T). Significant decrements were also identified in sperm viability and motility, chromatin, antioxidant capacity, mitochondrial membrane potential, mitochondrial membrane permeability transition pore (MPTP), and respiratory chain Complexes II and IV. CONCLUSIONS: Our data indicated that occupational CS2 exposure can exert deleterious effects on male sexual hormones and sperm quality, and mitochondrial dysfunction may play a vital role in this process.

DEVELOPMENT AND IMPLEMENTATION OF A PRACTICAL PUBLIC HEALTH TRAINING SYSTEM IN CHINA.

Public health education is becoming an increasing priority among educators of medicine. In China, little attention has been paid to public health education reform. A new public health training system was introduced in China in 2007. We conducted this study during 2006-2012 to evaluate the graduate core competencies under the new system. Data were collected from 231 graduates and 49 public health agencies. The 144 graduates who enrolled in 2006 and were trained under the old system constituted the control group; the 87 graduates who enrolled in 2007 and were trained under the new system constituted the experimental group. Surveys of graduate core competencies found analyzing and solving problems in the laboratory, conducting on-site practice and learning new technologies were the top three abilities most expected by public health agencies. After 5-year practical ability training, the graduates in the experimental group had better performance; on-site practical ability and laboratory practical ability increased significantly by 24.5% and 20.0%, respectively. Three other important competencies also improved: designing epidemiologic surveys, collecting information from the literature and doing statistical analyses. However, preventing and controlling common diseases and dealing with emergencies remained weak. These results show the new training system should be continued, but revisions are needed to improve this training system, especially in the areas of preventing and controlling common diseases and dealing with emergencies.

[Removal of triclosan with the method of UV/ClO2 and its degradation products].

The UV/ClO2 process for triclosan ( TCS) removal was studied. The influences of several factors such as the initial pH, dose of ClO2, initial concentration of TCS and humic acid( HA) on TCS degradation in the UV/ClO2 combined process were discussed. The results showed that the UV/ClO2 process could effectively remove TCS and had a synergistic effect. When the light intensity was 6.5 µW x Cm(-2), the dose of ClO2 was 0. 5 mg x L(-1) and the concentration of TCS was 300 µg x L(-1), when UV and ClO2 were applied alone, the TCS removal rates within 1 min were only 5.23% and 84.93% respectively. The removal rate reached up to 99.13% after 1 min degradation using the UV/ClO2 combined process. In test conditions ( pH 6-9), the removal rate increased from 99.4% to 99. 63% with the increase of pH. Increasing dose of CIO2 could promote TCS removal. When the dose of ClO2 was 0.5-1.5 mg x L(-1), the removal rate was increased from 98.1% to 99.89%. The initial concentration of TCS was negatively correlated with the removal rate. When the initial concentration increased from 100 - 500 µg x L(-1), the removal rate of TCS was decreased from 99.98% to 94.39%. Low concentration of humic acid was beneficial to the removal of TCS, and high concentration of it had the opposite effect. Degradation products of TCS were investigated by GC/MS. Degradation of TCS by the processes of UV, ClO2 and UV/ClO2 also indicated that the main degradation products of the TCS were 2, 4-dichlorophenol (2,4-DCP), 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD), etc.

Role of Endoplasmic reticulum apoptotic pathway in testicular Sertoli cells injury induced by Carbon disulfide.

The exposure of Carbon disulfide (CS2) is associated with germ cell injury and male infertility in animals and humans. However, the molecular mechanism is currently unknown. This study show here that CS2-induced Sertoli cells injury via Endoplasmic reticulum (ER) apoptotic pathway. SD male rats were exposed to doses of CS2 (0, 50, 250, 1250mgm(-3)) for 4weeks. After treatment, loose structures of seminiferous tubules and disordered cell arrangements were observed by light microscopy. Ultrastructural lesions, deformed chromatins and vacuoles formed from swollen ER were observed by electron microscopy. After primary culture of Sertoli cells, a dose-dependent increased apoptosis were found. The increased activity of Caspase 3, accumulation of intracellular Ca(2+), up-regulation of mRNA and protein expressions of ER apoptotic relative molecules (Calpain 2, Cleaved-Caspase 12, GRP78 and CHOP) were also found in this study. Altogether, our findings indicated that ER apoptotic pathway played an important role in CS2-induced Sertoli cell impairment.

Carbon disulfide induces rat testicular injury via mitochondrial apoptotic pathway.

Carbon disulfide (CS2), one of the most important volatile organic chemicals, was shown to have serious impairment to male reproductive system. But the underline mechanism is still unclear. In the present study, we aim to investigate the male germ cell apoptosis induced by CS2 exposure alone and by co-administration with cyclosporin A (CsA), which is the inhibitor of membrane permeability transition pore (MPTP). It was shown that CS2 exposure impaired ultrastructure of germ cells, increased the numbers of apoptotic germ cells, accumulated intracellular level of calcium, elevated ROS level, and increased activities of complexes of respiratory chain. Meanwhile, exposure to CS2 dramatically decreased the mitochondrial transmembrane potential (ΔΨm) and levels of ATP and MPTP opening. Exposure to CS2 can also cause a significantly dose-dependent increase in the expression levels of Bax, Cytc, Caspase-9, and Caspase-3, but decreased the expression level of Bcl-2. Moreover, co-administration of CsA with CS2 can reverse or alleviate the above apoptotic damage effects of CS2 on testicular germ cells. Taken together, our findings suggested that CS2 can cause damage to testicular germ cells via mitochondrial apoptotic pathway, and MPTP play a crucial role in this process.

[Effect of carbon disulfide on mitochondrial respiratory chain in spermatogenic cells in male rats].

OBJECTIVE: To investigate the effect of carbon disulfide (CS(2)) on the mitochondrial respiratory chain in testicular spermatogenic cells in male rats and to explore the possible mechanism of reproductive system damage caused by CS(2) in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were randomly divided into four groups: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and mitochondrial protein in spermatogenic cells were extracted; the levels of mitochondrial respiratory chain enzyme complex I∼V were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of mitochondrial respiratory chain enzyme complex I∼V in spermatogenic cells (P < 0.05). There were no significant differences in the levels of respiratory chain enzyme complex I∼IV between the CS(2) exposure groups (P < 0.05), but the level of respiratory chain enzyme complex V rose significantly as the concentration of CS(2) increased (P<0.05). CONCLUSION: Various levels of CS(2) exposure may increase the levels of mitochondrial respiratory chain enzyme complex in testicular spermatogenic cells among male rats, thus affecting the normal oxidative phosphorylation in mitochondria.

[Effect of carbon disulfide on mitochondrial apoptosis-related proteins in cytoplasm of testicular tissue among male rats].

OBJECTIVE: To investigate the role of mitochondrial pathway in the apoptosis of spermatogenic cells induced by inhalation of carbon disulfide in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were divided into four groups according to their body weights: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and cytoplasmic proteins were extracted; the levels of apoptosis-inducing factor (AIF), cytochrome c (cyto c), Bcl-2, Bax, procaspase-9, and procaspase-3 were measured by Western blot, and the activities of caspase-9 and caspase-3 were measured using a test kit. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of cyto c in the cytoplasm of testicular tissue (P<0.05); in the 250 mg/m(3) CS(2) exposure group, the Bax/Bcl-2 ratio and activities of caspase-9 and caspase-3 increased significantly (P<0.05), and the content of procaspase-9 and procaspase-3 decreased significantly (P<0.05); in the 1250 mg/m(3) CS(2) exposure group, the relative expression levels of Bax and AIF in cytoplasm increased significantly (P<0.05), and the expression level of Bcl-2 decreased significantly (P<0.05). CONCLUSION: Mitochondrial pathway plays an important role in the CS(2)-induced apoptosis of spermatogenic cells in testicular tissue among male rats.