Glutathione S-Transferase α4 Alleviates Hyperlipidemia- Induced Vascular Neointimal Hyperplasia in Arteriovenous Grafts via Inhibiting Endoplasmic Reticulum Stress.

Neointimal hyperplasia causes the failure of coronary artery bypass grafting (CABG). Our previous studies have found that endothelial dysfunction is one candidate for triggering neointimal hyperplasia, but which factors are involved in this process is unclear. Glutathione S-transferase α4 (GSTA4) play an important role in metabolizing 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product, which causes endothelial dysfunction or death. Here, we investigated the role of GSTA4 in neointima formation after arteriovenous grafts (AVGs) with or without high-fat diet (HFD). Compared with normal diet (ND), HFD caused endothelial dysfunction and increased neointima formation, concomitantly accompanied by downregulated expression of GSTA4 at the mRNA and protein levels. In vitro, overexpression of GSTA4 attenuated 4-HNE-induced endothelial dysfunction and knockdown of GSTA4 aggravated endothelial dysfunction. Furthermore, silencing GSTA4 expression facilitated the activation of 4-HNE induced endoplasmic reticulum stress (ERS) and inhibition of ERS pathway alleviated 4-HNE-induced endothelial dysfunction. Additionally, compared with wild-type (WT) mice, mice with knockout of endothelial-specific GSTA4 (GSTA4 EC KO) exhibited exacerbated vascular endothelial dysfunction and increased neointima formation caused by HFD. Together, these results demonstrate the critical role of GSTA4 in protecting the function of endothelial cells and in alleviating hyperlipidemia-induced vascular neointimal hyperplasia in arteriovenous grafts.

N-Acetylcysteine Attenuates Sepsis-Induced Muscle Atrophy by Downregulating Endoplasmic Reticulum Stress.

(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused by several diseases, whereas its effect on sepsis-induced muscle atrophy has not been reported. The present study investigated the effect of NAC on sepsis-induced muscle atrophy and its possible mechanisms. (2) Methods: The effect of NAC on sepsis-induced muscle atrophy was assessed in vivo and in vitro using cecal ligation and puncture-operated (CLP) C57BL/6 mice and LPS-treated C2C12 myotubes. We used immunofluorescence staining to analyze changes in the cross-sectional area (CSA) of myofibers in mice and the myotube diameter of C2C12. Protein expressions were analyzed by Western blotting. (3) Results: In the septic mice, the atrophic response manifested as a reduction in skeletal muscle weight and myofiber cross-sectional area, which is mediated by muscle-specific ubiquitin ligases-muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle ring finger 1 (MuRF1). NAC alleviated sepsis-induced skeletal muscle wasting and LPS-induced C2C12 myotube atrophy. Meanwhile, NAC inhibited the sepsis-induced activation of the endoplasmic reticulum (ER) stress signaling pathway. Furthermore, using 4-Phenylbutyric acid (4-PBA) to inhibit ER stress in LPS-treated C2C12 myotubes could partly abrogate the anti-muscle-atrophy effect of NAC. Finally, NAC alleviated myotube atrophy induced by the ER stress agonist Thapsigargin (Thap). (4) Conclusions: NAC can attenuate sepsis-induced muscle atrophy, which may be related to downregulating ER stress.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

Visual-motor integration in children with unilateral cerebral palsy: application of the computer-aided measure of visual-motor integration.

BACKGROUND: Children with unilateral cerebral palsy (UCP) are encouraged to participate in the regular school curriculum. However, even when using the less-affected hand for handwriting, children with UCP still experience handwriting difficulties. Visual-motor integration (VMI) is a predictor of handwriting quality. Investigating VMI in children with UCP is important but still lacking. Conventional paper-based VMI assessments is subjective and use all-or-nothing scoring procedures, which may compromise the fidelity of VMI assessments. Moreover, identifying important shapes that are predictive of VMI performance might benefit clinical decision-making because different geometric shapes represent different developmental stepping stones of VMI. Therefore, a new computer-aided measure of VMI (the CAM-VMI) was developed to investigate VMI performance in children with UCP and to identify shapes important for predicting their VMI performance. METHODS: Twenty-eight children with UCP and 28 typically-developing (TD) children were recruited. All participants were instructed to complete the CAM-VMI and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI). The test items of the CAM-VMI consisted of nine simple geometric shapes related to writing readiness. Two scores of the CAM-VMI, namely, Error and Effort, were obtained by image registration technique. The performances on the Beery-VMI and the CAM-VMI of children with UCP and TD children were compared by independent t-test. A series of stepwise regression analyses were used to identify shapes important for predicting VMI performance in children with UCP. RESULTS: Significant group differences were found in both the CAM-VMI and the Beery-VMI results. Furthermore, Error was identified as a significant aspect for predicting VMI performance in children with UCP. Specifically, the square item was the only significant predictor of VMI performance in children with UCP. CONCLUSIONS: This study was a large-scale study that provided direct evidence of impaired VMI in school-aged children with UCP. Even when using the less-affected hand, children with UCP could not copy the geometric shapes as well as TD children did. The copied products of children with UCP demonstrated poor constructional accuracy and inappropriate alignment. Furthermore, the predictive model suggested that the constructional accuracy of a copied square is an important predictor of VMI performance in children with UCP.

Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application.

It is now understood that hemolysis and the subsequent release of heme into circulation play a critical role in driving the progression of various diseases. Hemopexin (HPX), a heme-binding protein with the highest affinity for heme in plasma, serves as an effective antagonist against heme toxicity resulting from severe acute or chronic hemolysis. In the present study, changes in HPX concentration were characterized at different stages of hemolytic diseases, underscoring its potential as a biomarker for assessing disease progression and prognosis. In many heme overload-driven conditions, such as sickle cell disease, transfusion-induced hemolysis, and sepsis, endogenous HPX levels are often insufficient to provide protection. Consequently, there is growing interest in developing HPX therapeutics to mitigate toxic heme exposure. Strategies include HPX supplementation when endogenous levels are depleted and enhancing HPX's functionality through modifications, offering a potent defense against heme toxicity. It is worth noting that HPX may also exert deleterious effects under certain circumstances. This review aims to provide a comprehensive overview of HPX's roles in the progression and prognosis of hematological diseases. It highlights HPX-based clinical therapies for different hematological disorders, discusses advancements in HPX production and modification technologies, and offers a theoretical basis for the clinical application of HPX.

Manganese-nitrogen co-doped biochar (MnN@BC) as particle electrode for three-dimensional (3D) electro-activation of peroxydisulfate: Active sites enhanced radical/non-radical oxidation.

A novel manganese-nitrogen co-doped biochar (MnN@BC) was synthesized and used as particle electrodes in three-dimensional (3D) electro-activation of peroxydisulfate (PDS) for the degradation of refractory organic pollutants. All the spectroscopy (EDS, XRD, XPS, FTIR, and Raman) results indicated that Mn-N nanoclusters were successfully deposited and embedded in BC. The material appeared graphitized structure with more defects after Mn-N doping. MnN@BC in 3D electro-activation of PDS (E/MnN@BC/PDS) exhibited excellent performance in carbamazepine (CBZ) removal, with removal efficiency and degradation rates of 96.84% and 0.0582 min-1, respectively. Besides, MnN@BC was favorable for adsorption, electron transfer, and reactive oxidizing species (ROS) formation. MnN@BC had good recyclability in the E/MnN@BC/PDS system by the recycled experiments and characterization. Furthermore, quenching experiments, probe experiments, and electron paramagnetic resonance (EPR) analyses suggested that •OH and 1O2 were the main ROS in the E/MnN@BC/PDS system, and the non-radical oxidation take a key part. In addition, this system achieved excellent CBZ degradation under wide pH range of 3-11, had good tolerance to natural organic matter and inorganic ions, and was efficient to various water matrices and other refractory organic pollutants. These findings provided new insights into particle electrode design and mechanisms enhancement in electro-activated PDS systems.

Endoplasmic reticulum stress promotes sepsis-induced muscle atrophy via activation of STAT3 and Smad3.

Endoplasmic reticulum (ER) stress is involved in skeletal muscle atrophy in various conditions, but the role of ER stress in sepsis-induced muscle atrophy is not well understood. In this study, we conducted experiments in wild-type (WT) mice and C/EBP homologous protein knockout (CHOP KO) mice to explore the role and mechanism of ER stress in sepsis-induced muscle atrophy. Cecal ligation and puncture (CLP) was used to establish a mouse model of sepsis. In WT mice, the body weight, muscle mass, and cross-sectional area of muscle fibers in CLP group both decreased significantly compared with sham group, which revealed that sepsis-induced dramatic muscle atrophy. Additionally, sepsis activated the ubiquitin-proteasome system (UPS), accompanied by the activation of ER stress. In vitro, inhibition of ER stress suppressed the activity of E3 ubiquitin ligases and alleviated the myotube atrophy. In vivo, CHOP KO also reduced the expression of E3 ubiquitin ligases and UPS-mediated protein degradation, and significantly attenuated sepsis-induced muscle atrophy. Deletion of CHOP also decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and Smad3, and inhibition of STAT3 and Smad3 partly reduced proteolysis caused by ER stress in vitro. These findings confirm that ER stress activates UPS-mediated proteolysis and promotes sepsis-induced muscle atrophy, which is partly achieved by activating STAT3 and Smad3.

Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet.

OBJECTIVE: Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts (AVGs), but the factors mediating this process are unclear. The purpose of this study was to investigate the role of endoplasmic reticulum stress (ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet (HFD) mice. METHODS: CCAAT-enhancer-binding protein-homologous protein (CHOP) knockout (KO) mice were created. Mice were fed with HFD to produce HFD model. AVGs model were applied in the groups of WT ND, WT HFD, and CHOP KO HFD. Human umbilical vein endothelial cells (HUVECs) were cultured with oxidized low density lipoprotein (ox-LDL) (40 mg/L) for the indicated time lengths (0, 6, 12, 24 h). ERS inhibitor tauroursodeoxycholic acid (TUDCA) was used to block ERS. Immunohistochemical staining was used to observe the changes of ICAM1. Changes of ERS were detected by real-time RT-PCR. Protein expression levels and ERS activation were detected by Western blotting. Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay. RESULTS: HFD increased neointima formation in AVGs associated with endothelial dysfunction. At the same time, ERS was increased in endothelial cells (ECs) after AVGs in mice consuming the HFD. In vitro, ox-LDL was found to stimulate ERS, increase the permeability of the EC monolayer, and cause endothelial dysfunction. Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL. In vivo, knockout of CHOP (CHOP KO) protected the function of ECs and decreased neointima formation after AVGs in HFD mice. CONCLUSION: Inhibiting ERS in ECs could improve the function of AVGs.

Astragaloside IV alleviates sepsis-induced muscle atrophy by inhibiting the TGF-ß1/Smad signaling pathway.

BACKGROUND: Muscle atrophy occurs in patients with sepsis and increases mortality and disability. Remission of muscle atrophy may improve the quality of life in patients with sepsis. Astragaloside IV (ASIV) has been shown to have excellent anti-inflammatory and anti-fibrotic effects and to reduce organ damage caused by sepsis. However, the effect of ASIV on sepsis-induced muscle atrophy has not been reported. Therefore, this study explored the pharmacological effects and mechanisms of ASIV in sepsis-induced muscle atrophy. METHODS: Cecal ligation and puncture (CLP) was used to establish a mouse model of sepsis and lipopolysaccharide (LPS)-stimulated C2C12 myotubes. After administration of ASIV, the body weight, tibialis anterior (TA) and gastrocnemius muscle weight and fiber cross-sectional area of the mice were measured. The diameter of myotubes was observed by immunofluorescence staining. ELISA was used to assess inflammatory factors in plasma and cell culture supernatants. RT-PCR and Western blotting were used to detect the expression of MuRF1, Atrogin-1 and TGF-ß1/Smad signaling pathway components in TA and C2C12 myotubes. RESULTS: Our study found that ASIV reduced serum inflammatory factors and improved survival in septic mice. ASIV alleviated muscle mass reduction, myofiber cross-sectional area reduction, and C2C12 myotube atrophy by inhibiting the expression of the E3 ubiquitin ligases MuRF1 and atrogin-1. In addition, we observed that ASIV inhibited TGF-ß1/Smad signaling. Inhibition of the TGF-ß1/Smad signaling pathway partly blocked the anti-muscle atrophy effect of ASIV. CONCLUSION: ASIV can alleviate sepsis-induced muscle atrophy, which may be related to the inhibition of the TGF-ß1/Smad signaling pathway.

Application of biochar as an innovative soil ameliorant in bioretention system for stormwater treatment: A review of performance and its influencing factors.

As an emerging environment functional material, biochar has become a research hotspot in environmental fields because of its excellent ecological and environmental benefits. Recently, biochar has been used as an innovative soil ameliorant in bioretention systems (BRS) to effectively enhance pollutant removal efficiency for BRS. This paper summarizes and evaluates the performance and involved mechanisms of biochar amendment in BRS with respect to the removal of nutrients (TN (34-47.55%) and PO43--P (47-99.8%)), heavy metals (25-100%), pathogenic microorganisms (Escherichia coli (30-98%)), and organic contaminants (77.2-100%). For biochar adsorption, the pseudo-second-order and Langmuir models are the most suitable kinetic and isothermal adsorption models, respectively. Furthermore, we analyzed and elucidated some factors that influence the pollutant removal performance of biochar-amended BRS, such as the types of biochar, the preparation process and physicochemical properties of biochar, the aging of biochar, the chemical modification of biochar, and the hydraulic loading, inflow concentration and drying-rewetting alternation of biochar-amended BRS. The high potential for recycling spent biochar in BRS as a soil ameliorant is proposed. Collectively, biochar can be used as an improved medium in BRS. This review provides a foundation for biochar selection in biochar-amended BRS. Future research and practical applications of biochar-amended BRS should focus on the long-term stability of treatment performances under field conditions, chemical modification with co-impregnated nanomaterials in biochar surface, and the durability, aging, and possible negative effects of biochar.

Bioretention system mediated by different dry-wet alterations on nitrogen removal: Performance, fate, and microbial community.

In laboratory experiments, the nitrogen migration and transformation in the stormwater bioretention system under different dry-wet alterations were studied. The removal efficiency showed that nitrogen could be removed efficiently in bioretention system under all dry-wet alterations, and the shorter antecedent dry days (ADDs) (1-5 days) were beneficial to the removal of nitrogen before plants decay, compared to the longer ADDs (7-22 days). Using a new method combined with Hydrus-1D model, water transport was simulated and nitrogen migration in bioretention system was quantified, indicating that NH4+-N was mainly removed in the planting layer, and the removal of NO3--N was occurred in the submerged layer. Fate experiment showed the main fate of the nitrogen was microorganisms (1-5 ADDs) and soil immobilization (7-22 ADDs). Microbial analysis showed that shorter ADDs (1-5 days) were suitable for Firmicutes growth, while Proteobacteria and Actinobacteria accounted for greater abundance under longer ADDs (7-22 days). Canonical correlation analysis (CCA) revealed the relationships between microbial community and environmental factors. Soil moisture content, soil organic matter (SOM), TN (water), root length, and NO3--N (water) were significantly correlated with bacterial community. This work may give new insights into nitrogen migration and transformation, and can provide a reference for the further mechanism study and construction of stormwater bioretention systems.

Development and Feasibility of a Kinect-Based Constraint-Induced Therapy Program in the Home Setting for Children With Unilateral Cerebral Palsy.

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child's less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system. Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design. Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children's perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly. Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention. Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility. Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP.

Nitrogen process in stormwater bioretention: the impact of alternate drying and rewetting on nitrogen migration and transformation.

Nitrogen migration and transformation in the stormwater bioretention system were studied in laboratory experiments, in which the effects of drying-rewetting were particularly investigated. The occurrence and distribution of nitrogen in the plants, the soil, and the pore water were explored under different drying-rewetting cycles. The results clearly showed that bioretention system could remove nitrogen efficiently in all drying-rewetting cycles. The incoming nitrogen could be retained in the topsoil (0-10 cm) and accumulated in the planted layer. However, the overlong dry periods (12 and 22 days) cause an increase in nitrate in the pore water. In addition, nitrogen is mostly stored in the plants' stem tissues. Up to 23.26% of the inflowing nitrogen can be immobilized in plant tissues after a dry period of 22 days. In addition, the relationships between nitrogen reductase activity in the soil and soil nitrogen content were explored. The increase of soil TN content could enhance the activity of nitrate reductase. Meanwhile, the activity of hydroxylamine reductase (HyR) could be enhanced with the increase of soil NO3- content. These results provide a reference for the future development of nitrogen transformation mechanism and the construction of stormwater bioretention systems.

The Effect of Heat Treatment on the Sensitized Corrosion of the 5383-H116 Al-Mg Alloy.

In this study, the effects of heat treatment and sensitized corrosion on the 5383-H116 Al-Mg alloy were investigated for temperatures ranging from 100 to 450 °C. The results show that the heat treatment temperature is the main factor that causes changes to the microstructure and mechanical strength of the 5383-H116 Al-Mg alloy, inducing ß-phase (Al3Mg2) precipitation in the form of a continuous layer along the grain boundaries. Intergranular corrosion was caused by the ß-phase of the grain boundary precipitation, and the corrosion susceptibility of the recrystallized structure was significantly higher than the corrosion susceptibility of the recovered structure. According to the conductivity values detected, ß-phase precipitation can enhance the 5383-H116 Al-Mg alloy conductivity, with the response due to structural dislocation density being higher than that due to the recrystallized structure. As such, the ß-phase precipitation after sensitization is more significant than the ß-phase precipitation prior to the sensitization, such that after sensitization, the conductivity rises to a significantly higher level than that exhibited by the recrystallization structure.

Insights into scanning probe high-field chemistry of diphenylgermane.

Experiments and simulations are used to elucidate a new class of chemical reactions occurring near the tip-sample interface during high field chemistry of diphenylgermane. Current data during writing and bias dependent growth rate are analyzed, supplemented with data from ionization mass spectrometry, and compared with the simulation results.

Stability, electronic structure, and optical property of surface passivated silicon nanowires: density functional calculation.

In this study, we have investigated the influence of surface passivation on the electronic structures of silicon nanowires (SiNWs) by using density functional theory within the generalized gradient approximation. The band gaps of the CH3- and Cl-passivated SiNWs are remarkably smaller than those of the similar-sized H-passivated SiNWs. The difference in band gap is attributed to the different surface states induced by the passivating radicals. The calculated adsorption spectra of SiNWs are sensitive to the passivation way. Our results also show that wire orientation only has slight influence on the relative thermal stability of SiNWs.

Confirmation of elimination of lymphatic filariasis by an IgG4 enzyme-linked immunosorbent assay with urine samples in Yongjia, Zhejiang Province and Gaoan, Jiangxi Province, People's Republic of China.

A sensitive and specific IgG4 enzyme-linked immunosorbent assay (ELISA) with urine samples has been reported. To confirm elimination of bancroftian filariasis, the ELISA was used in a study conducted in Yongjia County and Gaoan City, People's Republic of China, where filariasis elimination was declared, with 10,409 students 5-16 years of age. The antibody positive rates were 0.08% in Yongjia and 0.34% in Gaoan. All positive samples were re-examined and found to be negative. Our results show that this ELISA is practical and useful for confirmation of the elimination of filariasis. If similar results are obtained in different filariasis-endemic countries, this method may be useful in global filariasis elimination programs.