Preparation and characterization of EI-Co/Zr@AC and the mechanisms underlying its removal for atrazine in aqueous solution.

Atrazine, a widely used herbicide in agriculture, is detrimental to both the ecological environment and human health owing to its extensive use, poor degradability, and biotoxicity. The technology commonly used to remove atrazine from water is activated carbon adsorption, but it has the problems of difficult recovery, secondary contamination, and a low removal rate. To efficiently remove atrazine from agricultural wastewater, in this study, a new environmental material, embedding immobilization (EI)-Co- and Zr-modified activated carbon powder (Co/Zr@AC), was prepared by immobilizing the bimetallic Co/Zr@AC via EI technique and employed to remove atrazine. When preparing EI-Co/Zr@AC, the single-factor experiment was conducted and determined the optimal preparation conditions: sodium alginate 2.5% (wt), calcium chloride 4.0% (wt), Co/Zr@AC 1.0% (wt), and bentonite 2.0% (wt). The prepared EI-Co/Zr@AC has a three-dimensional mesh structure and many pores and also possesses good mass transfer performance and mechanical properties. The removal efficiency by EI-Co/Zr@AC for the removal of 5.0 mg/L atrazine from 50 mL was 94.1% at pH 7.0 and 25°C, with an EI-Co/Zr@AC dosage of 0.8 g. The mechanistic study showed that the pseudo-second-order kinetic model could describe the removal process better than the pseudo-first-order kinetic model, and the Freundlich isotherm model fit better than other isotherm models. Additionally, the synthesized EI-Co/Zr@AC spheres demonstrated good reusability, with the atrazine removal rate remaining 70.4% after five cycles, and the mechanical properties of the spheres were stable.

Functional Bimetal/Carbon Composites Co/Zr@AC for Pesticide Atrazine Removal from Water.

Atrazine is a toxic and refractory herbicide that poses threats to human health and the ecological environment. In order to efficiently remove atrazine from water, a novel material, Co/Zr@AC, was developed. This novel material is prepared by loading two metal elements, cobalt and zirconium, onto activated carbon (AC) through solution impregnation and high-temperature calcination. The morphology and structure of the modified material were characterized, and its ability to remove atrazine was evaluated. The results showed that Co/Zr@AC had a large specific surface area and formed new adsorption functional groups when the mass fraction ratio of Co2+:Zr4+ in the impregnating solution was 1:2, the immersion time was 5.0 h, the calcination temperature was 500 °C, and the calcination time was 4.0 h. During the adsorption experiment on 10 mg/L atrazine, the maximum adsorption capacity of Co/Zr@AC was shown to be 112.75 mg/g and the maximum removal rate was shown to be 97.5% after 90 min of the reaction at a solution pH of 4.0, temperature of 25 °C, and Co/Zr@AC concentration of 60.0 mg/L. In the kinetic study, the adsorption followed the pseudo-second-order kinetic model (R2 = 0.999). The fitting effects of Langmuir and Freundlich isotherms were excellent, indicating that the process of Co/Zr@AC adsorbing atrazine also conformed to two isotherm models, so the adsorption of atrazine by Co/Zr@AC had multiple effects including chemical adsorption, mono-molecular layer adsorption, and multi-molecular layer adsorption. After five experimental cycles, the atrazine removal rate was 93.9%, indicating that Co/Zr@AC is stable in water and is an excellent novel material that can be used repeatedly.

Immobilization of Biomass Materials for Removal of Refractory Organic Pollutants from Wastewater.

In the field of environmental science and engineering, microorganisms, enzymes and algae are promising biomass materials that can effectively degrade pollutants. However, problems such as poor environmental adaptability, recycling difficulties, and secondary pollution exist in the practical application of non-immobilized biomass materials. Biomass immobilization is a novel environmental remediation technology that can effectively solve these problems. Compared with non-immobilized biomass, immobilized biomass materials have the advantages of reusability and stability in terms of pH, temperature, handling, and storage. Many researchers have studied immobilization technology (i.e., methods, carriers, and biomass types) and its applications for removing refractory organic pollutants. Based on this, this paper reviews biomass immobilization technology, outlines the mechanisms and factors affecting the removal of refractory organic pollutants, and introduces the application of immobilized biomass materials as fillers for reactors in water purification. This review provides some practical references for the preparation and application of immobilized biomass materials and promotes further research and development to expand the application range of this material for water purification.

Relationship among Child Maltreatment, Parental Conflict, and Mental Health of Children during the COVID-19 Lockdown in China.

Children are more likely to experience maltreatment and parental conflict in a pandemic context, which can exacerbate their vulnerability to psychological disorders. The purpose of the present study was to examine mental health symptoms in children aged 0 to 10 years and consider related factors from the perspectives of maltreatment and parental conflict during the COVID-19 lockdown. Participants were 1286 parents aged 18 years and over with children aged 0 to 10 years were included. Several multivariable linear regressions were used to analyze the data. The largest variance in child mental health was explained by child maltreatment, as more maltreatment predicted higher reported psychological problems (standardized beta = 0.49, P < 0.001). Comparatively, parental conflict predicted less variance in mental health problems than maltreatment (standardized beta = 0.18, P < 0.001). Children who experienced more maltreatment experience and exposure to COVID-19 showed elevated levels of mental health symptoms (standardized beta = 0.06, p < 0.05), as did those who experienced parental conflict and pandemic exposure (standardized beta = 0.06, p < 0.05). The findings highlight that tailored programs that focus on a healthy family environment and strategic parental support services may be particularly effective in reducing children's mental health problems due to COVID-19 exposure.

Detecting and Measuring Depression on Social Media Using a Machine Learning Approach: Systematic Review.

BACKGROUND: Detection of depression gained prominence soon after this troublesome disease emerged as a serious public health concern worldwide. OBJECTIVE: This systematic review aims to summarize the findings of previous studies concerning applying machine learning (ML) methods to text data from social media to detect depressive symptoms and to suggest directions for future research in this area. METHODS: A bibliographic search was conducted for the period of January 1990 to December 2020 in Google Scholar, PubMed, Medline, ERIC, PsycINFO, and BioMed. Two reviewers retrieved and independently assessed the 418 studies consisting of 322 articles identified through database searching and 96 articles identified through other sources; 17 of the studies met the criteria for inclusion. RESULTS: Of the 17 studies, 10 had identified depression based on researcher-inferred mental status, 5 had identified it based on users' own descriptions of their mental status, and 2 were identified based on community membership. The ML approaches of 13 of the 17 studies were supervised learning approaches, while 3 used unsupervised learning approaches; the remaining 1 study did not describe its ML approach. Challenges in areas such as sampling, optimization of approaches to prediction and their features, generalizability, privacy, and other ethical issues call for further research. CONCLUSIONS: ML approaches applied to text data from users on social media can work effectively in depression detection and could serve as complementary tools in public mental health practice.

The Relationship Between Being Bullied and Addictive Internet Use Among Chinese Rural Adolescents: The Mediating Effect of Adult Attachment.

Internet addiction among adolescents is an emerging public health issue. The aim of this study was to examine the relationship between being bullied and internet addiction, and further to test the mediating effect of adult attachments on this relationship among Chinese rural adolescents. A total of 1,270 adolescents from three high schools in Henan province were recruited as subjects. Internet addiction was measured by Young's internet addiction scale. This study showed that the prevalence of being bullied and addictive internet use among the recruited Chinese rural adolescents were 41.97% and 11.34%, respectively. Being bullied was significantly associated with internet addition. Adult attachment was found to mediate the association between being bullied and internet addiction. Higher anxiety attachment and lower close-dependent attachment partially explained the higher risk of internet addiction among the Chinese rural adolescents being bullied. This study suggests that the experience of being bullied can increase the risk of addictive internet use and that this risk can be mediated through adult attachments. This discovery supports the adoption of effective prevention programs to decrease school bullying and to improve adult attachments for adolescents in China and other countries.

Effects of Supplemental Lighting on Potassium Transport and Fruit Coloring of Tomatoes Grown in Hydroponics.

Supplemental blue/red lighting accelerated fruit coloring and promoted lycopene synthesis in tomato fruits. Potassium (K) is the most enriched cation in tomato fruits, and its fertigation improved tomato yield and fruit color. However, the effects of supplemental lighting on K uptake and transport by tomatoes and whether supplemental lighting accelerates fruit coloring through enhancing K uptake and transport are still unclear. We investigated the effects of supplemental light-emitting diode (LED) lighting (SL; 100% red, 100% blue; 75% red combined 25% blue) on K uptake in roots and transport in the fruits as well as the fruit coloring of tomatoes (Micro-Tom) grown in an experimental greenhouse in hydroponics. The use of red SL or red combined blue SL enhanced K uptake and K accumulation as well as carotenoid (phytoene, lycopene, γ-carotene, and ß-carotene) content in fruits by increasing photosynthesis, plant growth, and fruit weight. The genes related to ethylene signaling were upregulated by red SL. Quantitative real-time PCR (qRT-PCR) results showed that K transporter genes (SlHAKs) are differentially expressed during fruit development and ripening. The highest-expressed gene was SlHAK10 when fruit reached breaker and ripening. SlHAK3 and SlHAK19 were highly expressed at breaker, and SlHAK18 was highly expressed at ripening. These might be related to the formation of tomato fruit ripening and quality. SlHAK4, SlHAK6, SlHAK8, and SlHAK9 were significantly downregulated with fruit ripening and induced by low K. The expression level of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 were significantly increased by blue SL or red combined blue SL during breaker and ripening. Blue SL or red combined blue SL increased content of phytoene, ß-carotene, α-carotene, and γ-carotene and accelerated fruit coloring by enhancing K uptake in roots and transport in fruits during fruit ripening. This was consistent with the expression level of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 during fruit development and ripening. The key genes of photoreceptors, light signaling transcript factors as well as abscisic acid (ABA) transduction induced by blue SL or red combined blue SL were consistent with the upregulated genes of SlHAK6, SlHAK10, SlHAK15, and SlHAK19 under blue SL and red combined blue SL. The K transport in tomato fruits might be mediated by light signaling and ABA signaling transduction. These results provide valuable information for fruit quality control and the light regulating mechanism of K transport and fruit coloring in tomatoes.

The longitudinal effect of sensory loss on depression among Chinese older adults.

BACKGROUND: Previous studies have suggested that sensory loss is linked to depression. However, most of these studies have been conducted in developed countries and the results are mixed. OBJECTIVES: The current study aims to examine the longitudinal relationship between hearing loss, vision loss, dual sensory loss, and depression among Chinese older adults over four years. METHODS: The data were obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 6353 Chinese older adults aged 60 years and over were included at baseline in this study. Self-reported hearing and vision status was used, and dual sensory loss was a combined variable of hearing loss and vision loss. Depressive symptoms were assessed by The Center for Epidemiologic Studies Depression Scale (CESD-10). The baseline relationship between sensory loss and depression was explored by logistic regression analyses. A logistic mixed model was used to assess whether baseline sensory loss was associated with incident depression for older adults with no depressive symptoms at baseline over four years. RESULTS: At baseline, vision loss (OR=1.46, 95%CI: 1.19-1.79) and dual sensory loss (OR=2.14, 95%CI: 1.77-2.58) were associated with depression, while hearing loss was not. After four years, vision loss (OR=1.60, 95%CI: 1.16-2.22) and dual sensory loss (OR=1.78, 95%CI: 1.32-2.41) were associated with incident depression. LIMITATIONS: Not all potential confounding factors are measured and adjusted in the analysis. Apart from that, all measurements of interest are self-reported scales. CONCLUSION: Vision loss and dual sensory loss are significantly associated with both onset and increased depressive symptoms over time, while hearing loss is not associated with depression. Interactions between all types of sensory loss and social activities are not significant. Our results suggest that target mental health intervention programs should be delivered to vision loss or dual sensory loss populations.

Is the psychological impact of exposure to COVID-19 stronger in adolescents with pre-pandemic maltreatment experiences? A survey of rural Chinese adolescents.

BACKGROUND: Since the COVID-19 outbreak at the end of 2019, it has evolved into a global pandemic with tremendous mental health impact besides the threats to people's physical health. OBJECTIVE: The aims were to examine whether exposure to COVID-19 predicts elevated levels of anxiety and post-traumatic stress symptoms and whether pre-pandemic maltreatment experiences exacerbate this impact on mental health in adolescents. PARTICIPANTS AND SETTING: The survey was conducted online from February 8 st to February 27th, 2020, and the questionnaires were distributed and retrieved through a web-based platform. This study includes a total of 6196 subjects, aged range from 11 to 18 years old. METHODS: Several multivariable linear regressions were used to analyse the data. RESULTS: The largest variance in PTSS and anxiety problems was explained by ACEs, with more pre-pandemic maltreatment experiences predicting more PTSS (effect size beta = 0.16∼0.27), and more anxiety (effect size beta = 0.32∼0.47). Experienced or subjective fear of exposure to COVID-19 predicted statistically significant variance in PTSS and anxiety, and standardized betas ranged from 0.04 to 0.09. Participants who had adverse childhood experiences and had experienced exposure to COVID-19 showed elevated PTSS. CONCLUSIONS: After pre-pandemic maltreatment experiences the impact of exposure to COVID-19 on mental health may be stronger. Scars from the past seem to be vulnerabilities during societal upheaval. We therefore suggest that when exposed to COVID-19 rural adolescents should get prioritized professional family support and mental health counseling in particular when they have experienced family abuse and neglect in childhood, even though such support is more difficult to organize in rural areas.

Attitudes toward aging, social support and depression among older adults: Difference by urban and rural areas in China.

BACKGROUND: The specific impacts of attitudes toward aging on depressive symptoms have not been widely reported in previous studies in China. OBJECTIVES: The aim is to examine the associations between attitudes toward aging, perceived social support, and depressive symptoms among older adults stratified by rural and urban dwelling. METHODS: This study used a cross-sectional data including 7209 participants, among which 64.6% were urban adults and 35.4% were rural adults. Several multiple liner regression models were used to analysis the data. Three social support types were analyzed as moderators of the relationship between the attitudes toward aging and depressive symptoms. RESULTS: Positive attitudes toward aging (ß=-0.139, P<0.001), negative attitudes toward aging (ß=0.284, P<0.001) were significantly associated with lower depressive symptoms among older Chinese adults. Support from family (ß=-0.087, P<0.001), friends (ß=-0.047, P<0.01) and the government (ß=-0.035, P<0.01) were all significantly associated with urban older adults' levels of depressive symptoms. Only family support (ß=-0.109, P<0.001) was associated with lower depressive symptoms among rural older adults'. In addition, family support buffered the effect of negative attitudes toward aging on depressive symptoms for all the older adults, while the moderation effects of support from friends and government only worked for urban elderly. LIMITATIONS: A cross-sectional design is limited to establish causal associations. CONCLUSIONS: Addressing depression among older adults should focus on improving attitudes toward aging and expanding the availability of social support. Moreover, deeper reforms are needed to address inequalities between urban and rural areas in China.

The Combined Impact of Gender and Age on Post-traumatic Stress Symptoms, Depression, and Insomnia During COVID-19 Outbreak in China.

The mental health problems might have been increased owing to the COVID-19 pandemic with the commencement of the year 2020, therefore, an epidemiological survey appraising the burden of mental health issues among the general population is imperative. This cross-sectional study attempts to reveal the underlying mental health conditions, such as Post-Traumatic Stress Symptoms (PTSS), depression, and insomnia, relating to the pandemic situation, and to further examine the combined effects of gender and age on the COVID-19 related mental health consequences. An online survey was conducted among 2,992 adults in China from February 1st 2020 to February 10th 2020. The study uses binary logistic regression to analyze the potential factors associated with PTSD, depression, and insomnia. The results indicate that the prevalence of PTSS, depression, and insomnia are 19.5, 26.9, and 19.6% respectively during the COVID-19. Men and women show different rates of PTSS and depression, whereas no insomnia is found in both males and females. The females above 50 years of age have a lower level of depressive symptoms (OR = 0.448, 95%CI: 0.220-0.911, Cohen's d = -0.443) as compared with females aged 18-25; while the highest effect sizes for PTSS (OR = 2.846, 95%CI: 1.725-4.695, Cohen's d = 0.537) and the depression (OR = 2.024, 95%CI: 1.317-3.111, Cohen's d = 0.314) are seen in males aged 26 to 30. Besides gender, education, living conditions, direct exposure to COVID-19, the post mental and the physical health condition is related to PTSS, depression, and insomnia. Our study suggests that high-risk groups, especially those having two or more related factors and young men, should be the focus of mental health intervention.

Hg tolerance and biouptake of an isolated pigmentation yeast Rhodotorula mucilaginosa.

A pigmented yeast R1 with strong tolerance to Hg2+ was isolated. Phylogenetic identification based on the analysis of 26S rDNA and ITS revealed R1 is a Rhodotorula mucilaginosa species. R1 was able to grow in the presence of 80 mg/L Hg2+, but the lag phase was much prolonged compared to its growth in the absence of Hg2+. The maximum Hg2+ binding capacity of R1 was 69.9 mg/g, and dead cells could bind 15% more Hg2+ than living cells. Presence of organic substances drastically reduced bioavailability of Hg2+ and subsequently decreased Hg2+ removal ratio from aqueous solution, but this adverse effect could be remarkably alleviated by the simultaneous process of cell propagation and Hg2+ biouptake with actively growing R1. Furthermore, among the functional groups involved in Hg2+ binding, carboxyl group contributed the most, followed by amino & hydroxyl group and phosphate group. XPS analysis disclosed the mercury species bound on yeast cells was HgCl2 rather than HgO or Hg0.

Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune activation.

The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.

The temporal and spatial profiles of cell loss following experimental spinal cord injury: effect of antioxidant therapy on cell death and functional recovery.

BACKGROUND: Traumatic spinal cord injury (SCI)-induced overproduction of endogenous deleterious substances triggers secondary cell death to spread damage beyond the initial injury site. Substantial experimental evidence supports reactive species (RS) as important mediators of secondary cell death after SCI. This study established quantitative temporal and spatial profiles of cell loss, characterized apoptosis, and evaluated the effectiveness of a broad spectrum RS scavenger - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and a combination of MnTBAP plus nitro-L-arginine to prevent cell loss and neurological dysfunction following contusion SCI to the rat spinal cord. RESULTS: By counting the number of surviving cells in spinal cord sections removed at 1, 6, 12, 24, 48, 72 h and 1 week post-SCI and at 0 - 4 mm from the epicenter, the temporal and spatial profiles of motoneuron and glia loss were established. Motoneurons continued to disappear over a week and the losses decreased with increasing distance from the epicenter. Significant glia loss peaked at 24 to 48 h post-SCI, but only at sections 0-1.5 mm from the epicenter. Apoptosis of neurons, motoneurons and astrocytes was characterized morphologically by double immuno-staining with cell-specific markers and apoptosis indicators and confirmed by transmission electron microscopy. DNA laddering, ELISA quantitation and caspase-3 activation in the spinal cord tissue indicated more intense DNA fragments and greater caspase-3 activation in the epicenter than at 1 and 2 cm away from the epicenter or the sham-operated sections. Intraperitoneal treatment with MnTBAP + nitro-L-arginine significantly reduced motoneuron and cell loss and apoptosis in the gray and white matter compared with the vehicle-treated group. MnTBAP alone significantly reduced the number of apoptotic cells and improved functional recovery as evaluated by three behavioral tests. CONCLUSIONS: Our temporal and spatial profiles of cell loss provide data bases for determining the time and location for pharmacological intervention. Our demonstration that apoptosis follows SCI and that MnTBAP alone or MnTBAP + nitro-L-arginine significantly reduces apoptosis correlates SCI-induced apoptosis with RS overproduction. MnTBAP significantly improved functional recovery, which strongly supports the important role of antioxidant therapy in treating SCI and the candidacy of MnTBAP for such treatment.

[Impacts of Mycobacterium tuberculosis with different virulence on expressions of ferroportin and ferritin in infected macrophages].

OBJECTIVE: To explore the time-dependent changes in the expressions of ferritin (Fn) and ferroportin (FPN) in macrophages infected with Mycobacterium (M.) tuberculosis of highly virulent strain (H37Rv strain) and Bacillus Calmette-Guerin (BCG) strain. METHODS: RAW264.7 macrophages were respectively infected with M. tuberculosis H37Rv strain and BCG strain. At 1, 6, 12, 18 and 24 h after infection, the contents of Fn and FPN in the infected macrophage culture supernatants of the two groups were detected using ELISA, and meanwhile, the expression of Fn in the infected macrophages of each group was determined using Western blotting. RESULTS: After the macrophages were infected with different strains, the expression of Fn in macrophages increased as time went by; at 1 h after infection, the Fn expression in the control group was significantly higher than that in the H37Rv group and the BCG group; at 6 h after infection, the Fn expression in the two infected groups were higher than that in the control group; at 12 h, the Fn expression in the H37Rv group was higher than that in the control group, the difference was statistically significant (P<0.05); at 18 and 24 h, the Fn expression was reduced in the order as H37Rv group > BCG group > control group (P<0.05). The expression of FPN decreased gradually as time went by. Compared with the normal control group, the expression in both H37Rv group and BCG group presented a lower level and H37Rv group < BCG group < control group (P<0.05). CONCLUSION: The infection of M.tuberculosis can lead to increased Fn expression and decreased FPN expression in macrophages, and the levels of Fn and FPN in the infected macrophages are both related to the strength of the virulence of M.tuberculosis.

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone.

BACKGROUND: Substantial experimental evidence supports that reactive species mediate secondary damage after traumatic spinal cord injury (SCI) by inducing oxidative stress. Removal of reactive species may reduce secondary damage following SCI. This study explored the effectiveness of a catalytic antioxidant - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) - in removing reactive oxygen species (ROS), reducing oxidative stress, and improving functional recovery in vivo in a rat impact SCI model. The efficiency of MnTBAP was also compared with that of methylprednisolone - the only drug used clinically in treating acute SCI. RESULTS: In vivo measurements of time courses of ROS production by microdialysis and microcannula sampling in MnTBAP, methylprednisolone, and saline (as vehicle control)-treated SCI rats showed that both agents significantly reduced the production of hydrogen peroxide, but only MnTBAP significantly reduced superoxide elevation after SCI. In vitro experiments further demonstrated that MnTBAP scavenged both of the preceding ROS, whereas methylprednisolone had no effect on either. By counting the immuno-positive neurons in the spinal cord sections immunohistochemically stained with anti-nitrotyrosine and anti-4-hydroxy-nonenal antibodies as the markers of protein nitration and membrane lipid peroxidation, we demonstrated that MnTBAP significantly reduced the numbers of 4-hydroxy-nonenal-positive and nitrotyrosine-positive neurons in the sections at 1.55 to 2.55 mm and 1.1 to 3.1 mm, respectively, rostral to the injury epicenter compared to the vehicle-treated animals. By behavioral tests (open field and inclined plane tests), we demonstrated that at 4 hours post-SCI treatment with MnTBAP and the standard methylprednisolone regimen both significantly increased test scores compared to those produced by vehicle treatment. However, the outcomes for MnTBAP-treated rats were significantly better than those for methylprednisolone-treated animals. CONCLUSIONS: This study demonstrated for the first time in vivo and in vitro that MnTBAP significantly reduced the levels of SCI-elevated ROS and that MnTBAP is superior to methylprednisolone in removing ROS. Removal of ROS by MnTBAP significantly reduced protein nitration and membrane lipid peroxidation in neurons. MnTBAP more effectively reduced neurological deficits than did methylprednisolone after SCI - the first most important criterion for assessing SCI treatments. These results support the therapeutic potential of MnTBAP in treating SCI.

Stability, disposition, and penetration of catalytic antioxidants Mn-porphyrin and Mn-salen and of methylprednisolone in spinal cord injury.

This study measured the time courses of concentration changes following administration of the catalytic antioxidants Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and Mn (III) 3-methoxy N, N' bis (salicyclidene) ethylenediamine chloride (EUK-134) in blood and cerebrospinal fluid (CSF) of rats with a spinal cord injury (SCI) and sham controls. Parallel measurements were made for methylprednisolone, the only drug presently used clinically for treating SCI. The time courses kinetically characterized the agents in their stability, disposition, and ability to penetrate the blood-spinal cord barrier (BSB). In both the SCI and control groups, MnTBAP was stable in CSF and in blood across the collection periods (10 h and 24 h, respectively) following administration. In the blood, [EUK-134] and [methylprednisolone] rapidly declined to near basal concentrations at 4 h and 2 h, respectively, post-administration. Therefore the order of stability in CSF and blood was MnTBAP >> EUK-134 > methylprednisolone. The maximum CSF/blood concentration ratios for EUK-134, methylprednisolone and MnTBAP post-administration were: 32 ± 3.1%, 19.2 ± 6.4%, and 4.42 ± 0.73% in the injured rats, and 22 ± 6.5%, 17.8 ± 2.9%, and 1.0 ± 0.5% in the sham control animals. This suggests an order of BSB penetration of EUK-134 > methylprednisolone >> MnTBAP. Despite much lower penetration by MnTBAP compared with EUK-134 and methylprednisolone, a lower dose of MnTBAP because of its stability provided a higher concentration in CSF than did the other agents given at higher doses. This finding supports further exploration of MnTBAP as a potential treatment for SCI.

Mn (III) tetrakis (4-benzoic acid) porphyrin protects against neuronal and glial oxidative stress and death after spinal cord injury.

This study explores the ability of a catalytic antioxidant, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to protect against neuronal and glial oxidative stress and death after spinal cord injury (SCI). Nine different doses of MnTBAP were administered into the intrathecal space of the rat spinal cord immediately following moderate SCI to establish dose - response curves for prevention of lipid peroxidation and neuron death. An optimal dose was determined by comparing the effectiveness of MnTBAP protection among doses. The optimal dose was then administered and the cords were removed 24 h post-administration and processed for staining. The cells in the cord sections at different distances from the epicenter were counted to obtain the spatial profiles of MnTBAP protection. Comparison of the counts between MnTBAP- and vehicle-treated groups in the sections double immuno-fluorescence-stained with oxidative and cellular markers demonstrated that MnTBAP significantly reduced numbers of nitrotyrosine- and DNP-positive (stained with an antibody against 2,4-dinitrophenyl hydrazine (DNPH)-labeled protein carbonyls) neurons, astrocytes, and oligodendrocytes. Comparison of the counts between the two treatments in the sections immuno-stained with cellular markers revealed that MnTBAP significantly increased numbers of neurons, motoneurons, astrocytes, and oligodendrocytes. MnTBAP more effectively reduced neuronal than glial cell death. Post-injury treatment with the optimal dose of MnTBAP at 6, 12, 24, 48, and 72 h post-SCI demonstrated that the effective time window for reducing protein nitration and neuron death was at least 12 h. Our results demonstrated that MnTBAP combats oxidative stress, thereby attenuating all types of cell death after SCI.

Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle.

The purpose of this study was to investigate the changes in the gene expression of Mitofusion (Mfn) 1 and 2 and Fission 1 (Fis1) and mitochondrial energy metabolism in response to altered energy demand during prolonged exercise in rat skeletal muscle. Male Sprague-Dawley rats were subjected to an acute bout of treadmill running at various durations and killed immediately or during recovery. Mfn1/2 and Fis1 mRNA and protein contents, reactive oxygen species (ROS) generation, state 3 and state 4 respiration rates, trans-innermembrane potential and ATP synthase activity were measured in isolated muscle mitochondria. We found that (1) Mfn1/2 mRNA contents were progressively decreased during 150 min of exercise, along with decreased Mfn 1 protein levels. Fis1 mRNA and protein contents showed significant increases after 120-150 min of exercise. These changes persisted through the recovery period up to 24 h. (2) Mitochondrial ROS generation and state 4 respiration showed progressive increases up to 120 min, but dropped at 150 min of exercise. (3) State 3 respiration rate and respiratory control index were unchanged initially but decreased at 150 and 120 min of exercise, respectively, whereas ATP synthase activity was elevated at 45 min and returned to resting level thereafter. Our data suggested that the gene expression of mitochondrial fusion and fission proteins in skeletal muscle can respond rapidly to increased metabolic demand during prolonged exercise, which could significantly affect the efficiency of oxidative phosphorylation.

Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by a metalloporphyrin.

This study presents quantitative temporal and spatial profiles of neuronal loss and apoptosis following a contusion spinal cord injury (50 g . cm). The profiles were evaluated by counting the cresol violet-stained surviving cells and the total number of TUNEL-positive cells and of TUNEL-positive neurons in sections 0- 4 mm from the epicenter and 1, 6, 12, 24, 48, and 72 hr and 1 week postinjury. We demonstrated that neurons continue to disappear over 1 week postinjury and that neuronal loss shifts to areas longer distances from the epicenter over time. TUNEL-positive cells in both gray and white matter appeared after 6 hr, gradually increased to a peak level after 48 hr, and declined by 72 hr postinjury. TUNEL-positive neurons peaked earlier and were present for 1 week, although the total number of neurons was reduced significantly by the end of the week. The neuronal loss and apoptosis were partially prevented by a metalloporphyrin [Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP)]. We demonstrated that MnTBAP (10 and 50 mg/kg, given intraperitoneally) significantly reduced neuronal death in the sections 1-2.5 mm rostral and 1 mm caudal from the epicenter compared with that in the vehicle-treated group, suggesting MnTBAP is more effective in the sections rostral than in those caudal to the epicenter. MnTBAP (10 mg/kg) significantly reduced the number of TUNEL-positive neurons in the sections 1 mm caudal from the epicenter. Our profiles provide a database for pharmacological intervention, and our results on MnTBAP treatment support an important role for antioxidant therapy in spinal cord injury.