Magneto-optical Properties of Chiral Co2Ln and Co3Ln2 (Ln = Dy and Er) Clusters.

A series of chiral heterometallic Ln-Co clusters, denoted as Co2Ln and Co3Ln2 (Ln = Dy and Er), were synthesized by reacting the chiral chelating ligand (R/S)-2-(1-hydroxyethyl)pyridine (Hmpm), CoAc2·4H2O, and Ln(NO3)3·6H2O. Co2Ln and Co3Ln2 exhibit perfect mirror images in circular dichroism within the 320-700 nm range. Notably, the Co2Er and Co3Er2 clusters display pronounced magnetic circular dichroism (MCD) responses of the hypersensitive f-f transitions 4I15/2-4G11/2 at 375 nm and 4I15/2-2H11/2 at 520 nm of ErIII ions. This study highlights the strong magneto-optical activity associated with hypersensitive f-f transitions in chiral 3d-4f magnetic clusters.

Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.

Neuronal iron overload contributes to synaptic damage and neuropsychiatric disorders. However, the molecular mechanisms underlying iron deposition in depression remain largely unexplored. Our study aims to investigate how nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) ameliorates hippocampal synaptic dysfunction and reduces brain functional connectivity (FC) associated with excessive iron in depression. We treated mice with chronic unpredictable mild stress (CUMS) with the iron chelator deferoxamine mesylate (DFOM) and a high-iron diet (2.5% carbonyl iron) to examine the role of iron overload in synaptic plasticity. The involvement of Nrf2 in iron metabolism and brain function was assessed using molecular biological techniques and in vivo resting-state functional magnetic resonance imaging (rs-fMRI) through genetic deletion or pharmacologic activation of Nrf2. The results demonstrated a significant correlation between elevated serum iron levels and impaired hippocampal functional connectivity (FC), which contributed to the development of depression-induced CUMS. Iron overload plays a crucial role in CUMS-induced depression and synaptic dysfunction, as evidenced by the therapeutic effects of a high-iron diet and DFOM. The observed iron overload in this study was associated with decreased Nrf2 levels and increased expression of transferrin receptors (TfR). Notably, inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Nrf2-/- mice exhibited compromised FC within the limbic system and the basal ganglia, particularly in the hippocampus, and inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Activation of Nrf2 restored iron homeostasis and reversed vulnerability to depression. Mechanistically, we further identified that Nrf2 deletion promoted iron overload via upregulation of TfR and downregulation of ferritin light chain (FtL), leading to BDNF-mediated synapse damage in the hippocampus. Therefore, our findings unveil a novel role for Nrf2 in regulating iron homeostasis while providing mechanistic insights into poststress susceptibility to depression. Targeting Nrf2-mediated iron metabolism may offer promising strategies for developing more effective antidepressant therapies.

Magnetic mesoporous polymelamine-formaldehyde resin as an adsorbent for endocrine disrupting chemicals.

A magnetic mesoporous poly(melamine-formaldehyde) composite (Fe3O4-mPMF) was prepared via grafting poly(melamine-formaldehyde) onto the surface of amino-functionalized magnetite (Fe3O4) nanoparticles. The material was characterized by scanning electron micrography, transmission electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, nitrogen adsorption-desorption isotherms, and thermogravimetric analysis. It has a large surface area, a typical mesoporous structure, and a high thermal stability. It was employed as a magnetic sorbent for the solid phase extraction of the following endocrine disrupting chemicals (EDCs): Bisphenol A, 4-tert-butylphenol, 4-tert-octylphenol and nonylphenol. The EDCs were then quantified by HPLC. Under the optimized conditions, the response to the EDCs is linear in the range of 0.5-100 ng·mL-1, and the limits of detection are 0.02-0.1 ng·mL-1. The high adsorption capability of the Fe3O4-mPMF is mainly attributed to multiple interactions including π-stacking, hydrogen bonding, and hydrophobic interactions. The method was applied to the extraction of EDCs from spiked river water and bottled juice samples. The results demonstrated that the Fe3O4-mPMF is an efficient adsorbent for the extraction of organic compounds with large conjugated π-system, plenty of hydrogen-bonding sites, and strong hydrophobicity. Graphical abstract A magnetic mesoporous polymelamine-formaldehyde composite (Fe3O4-mPMF) was prepared and employed as a magnetic sorbent for the solid phase extraction of endocrine disrupting chemicals from river water and bottled juice samples prior to high-performance liquid chromatographic analysis.

Indoleamine 2, 3-dioxygenase 1 activation in macrophage exacerbates hepatic ischemia-reperfusion injury by triggering hepatocyte ferroptosis.

BACKGROUND: Hepatic Ischemia-reperfusion (I/R) injury, critical challenge in liver surgery and transplantation, exerts a significant impact on the prognosis and survival of patients. Inflammation and cell death play pivotal roles in pathogenesis of hepatic I/R injury. Indoleamine 2, 3-dioxygenase 1 (IDO-1), a key enzyme involved in the kynurenine pathway, has been extensively investigated for its regulatory effects on innate immune responses and cell ferroptosis. However, the precise involvement of IDO-1 in hepatic I/R injury remains unclear. METHODS: IDO-1 knockout mice were generated to establish a murine model of liver partial warm ischemia and reperfusion, while an in vitro Hypoxia/Reoxygenation (H/R) model was employed to simulate ischemia/reperfusion injury. RESULTS: The involvement of ferroptosis was observed to be involved in hepatic I/R injury, and effective mitigation of liver injury was achieved through the inhibition of ferroptosis. In the context of hepatic I/R injury, up-regulation of IDO-1 was found in macrophages exhibiting prominent M1 polarization and impaired efferocytosis. Deficiency or inhibition of IDO-1 alleviated hepatocytes ferroptosis and M1 polarization induced by hepatic I/R injury, while also enhancing M2 polarization and promoting efferocytosis in macrophages. Furthermore, depletion of macrophages attenuated ferroptosis in hepatocytes induced by hepatic I/R injury. CONCLUSION: This study highlights the crucial role of IDO-1 activation in macrophages in triggering ferroptosis in hepatocytes during hepatic ischemia-reperfusion injury. Our findings suggest that targeting IDO-1 could be a promising therapeutic strategy for mitigating hepatic I/R injury associated with liver surgery and transplantation.

Systematic establishment and verification of an epithelial-mesenchymal transition gene signature for predicting prognosis of oral squamous cell carcinoma.

Objective: Epithelial-mesenchymal transition (EMT) is linked to an unfavorable prognosis in oral squamous cell carcinoma (OSCC). Here, we aimed to develop an EMT gene signature for OSCC prognosis. Methods: In TCGA dataset, prognosis-related EMT genes with p < 0.05 were screened in OSCC. An EMT gene signature was then conducted with LASSO method. The efficacy of this signature in predicting prognosis was externally verified in the GSE41613 dataset. Correlations between this signature and stromal/immune scores and immune cell infiltration were assessed by ESTIMATE and CIBERSORT algorithms. GSEA was applied for exploring significant signaling pathways activated in high- and low-risk phenotypes. Expression of each gene was validated in 40 paired OSCC and normal tissues via RT-qPCR. Results: A prognostic 9-EMT gene signature was constructed in OSCC. High risk score predicted poorer clinical outcomes than low risk score. ROCs confirmed the well performance on predicting 1-, 3- and 5-year survival. Multivariate cox analysis revealed that this signature was independently predictive of OSCC prognosis. The well predictive efficacy was validated in the GSE41613 dataset. Furthermore, this signature was distinctly related to stromal/immune scores and immune cell infiltration in OSCC. Distinct pathways were activated in two subgroups. After validation, AREG, COL5A3, DKK1, GAS1, GPX7 and PLOD2 were distinctly upregulated and SFRP1 was downregulated in OSCC than normal tissues. Conclusion: Our data identified and verified a robust EMT gene signature in OSCC, which provided a novel clinical tool for predicting prognosis and several targets against OSCC therapy.

Spatiotemporal knowledge teacher-student reinforcement learning to detect liver tumors without contrast agents.

Detecting Liver tumors without contrast agents (CAs) has shown great potential to advance liver cancer screening. It enables the provision of a reliable liver tumor-detecting result from non-enhanced MR images comparable to the radiologists' results from CA-enhanced MR images, thus eliminating the high risk of CAs, preventing an experience gap between radiologists and simplifying clinical workflows. In this paper, we proposed a novel spatiotemporal knowledge teacher-student reinforcement learning (SKT-RL) as a safe, speedy, and inexpensive contrast-free technology for liver tumor detection. Our SKT-RL builds a teacher-student framework to realize the exploring of explicit liver tumor knowledge from a teacher network on clear contrast-enhanced images to guide a student network to detect tumors from non-enhanced images directly. Importantly, our STK-RL enables three novelties in aspects of construction, transferring, and optimization to tumor knowledge to improve the guide effect. (1) A new spatiotemporal ternary knowledge set enables the construction of accurate knowledge that allows understanding of DRL's behavior (what to do) and reason (why to do it) behind reliable detection within each state and between their related historical states. (2) A novel pixel momentum transferring strategy enables detailed and controlled knowledge transfer ability. It transfers knowledge at a pixel level to enlarge the explorable space of transferring and control how much knowledge is transferred to prevent over-rely of the student to the teacher. (3) A phase-trend reward function designs different evaluations according to different detection phases to optimal for each phase in high-precision but also allows reward trend to constraint the evaluation to improve stability. Comprehensive experiments on a generalized liver tumor dataset with 375 patients (including hemangiomas, hepatocellular carcinoma, and normal controls) show that our novel SKT-RL attains a new state-of-the-art performance (improved precision by at least 4% when comparing the six recent advanced methods) in the task of liver tumor detection without CAs. The results proved that our SKT-DRL has greatly promoted the development and deployment of contrast-free liver tumor technology.

Minimally invasive laminar lift and posterior cervical laminoplasty via the intermuscular approach: a canine model study.

PURPOSE: This study aimed to develop a minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach using a canine model. METHODS: Six Alaskan dogs were used for developing the surgical approach. The bilateral laminae of C3-7 were cut with an ultrasonic osteotome and fixed with bilateral plates to maintain the lamina lifting and reshape a wider spinal canal. The important structures, such as ligaments, supraspinous ligaments, interspinous ligaments, and ligamentum flavum were preserved. The therapeutic effect was evaluated by preoperative and postoperative imaging results and neck mobility. RESULTS: The surgical procedures were all successfully performed in the 6 animals. All the dogs survived well within 1 year of postoperative follow-up. The postoperative neck mobility was as good as the preoperative one. Computed tomography results showed that the anteroposterior diameter of the spinal canal was successfully enlarged and maintained well. CONCLUSIONS: The minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach was feasible in a canine model, which might be applied in clinical practice.

Poria cocos polysaccharides rescue pyroptosis-driven gut vascular barrier disruption in order to alleviates non-alcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos polysaccharides (PCP) are abundant in Poria cocos (Schw.) Wolf (Poria). This is a common traditional Chinese medicine used to treat gastrointestinal and liver diseases. Poria cocos dispel dampness and enhance gastrointestinal functions, strongly affecting the treatment of non-alcoholic fatty liver disease. Still, the mechanism is not yet clear. AIM OF THE STUDY: The latest research found that protecting the integrity of the intestinal barrier can slow down the progression of non-alcoholic fatty liver disease (NAFLD). Hence, our research ought to explore the protective mechanism of PCP on the intestinal barrier under a high-fat diet and to clarify the relationship between intestinal barrier damage and steatohepatitis. MATERIALS AND METHODS: H&E staining was done to evaluate pathological damage, whereas Nile red and oil red O staining was conducted to evaluate hepatic fat infiltration. Immunofluorescence staining and immunohistochemical staining were used to detect protein expression and locations. Bone marrow-derived macrophages were isolated for in vitro experiments. ONOO- and ROS fluorescent probes and MDA, SOD, and GSH kits assessed the levels of nitrogen and oxidative stress. LPS levels were detected with a Limulus Amebocyte Lysate assay. The Western blot analysis and reverse transcription-quantitative PCR detected the expression of related proteins and genes. The Elisa kit detected the level of the inflammatory factors in the cell supernatant. For the vivo NAFLD experiments, in briefly, mice were randomly chosen to receive either a High-fat diet or control diet for 12 weeks. Drug treatments started after 4 weeks of feeding. Zebrafish larvae were raised separately in fish water or 7 mM thioacetamide as the control or model group for approximately 72 h. In the therapy groups, different concentrations of PCP were added to the culture environment at the same time. RESULTS: In zebrafish, we determined the safe concentration of PCP and found that PCP could effectively reduce the pathological damage in the liver and intestines induced by the NAFLD model. In mice, PCP could slow down weight gain, hyperlipidemia, and liver steatosis caused by a high-fat diet. More importantly, PCP could reduce the destruction of the gut-vascular barrier and the translocation of endotoxins caused by a high-fat diet. Further, we found that PCP could inhibit intestinal pyroptosis by regulating PARP-1. Pyroptosis inhibitors, such as MCC950, could effectively protect the intestinal and liver damage induced by a high-fat diet. We also found that pyroptosis mainly occurred in intestinal macrophages. PCP could effectively improve the survival rate of bone marrow-derived macrophages in a high-fat environment and inhibit pyroptosis. CONCLUSIONS: These results indicated that PCP inhibited the pyroptosis of small intestinal macrophages to protect the intestinal barrier integrity under a high-fat diet. This resulted in decreased endotoxin translocation and progression of steatohepatitis.

Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation.

Combination of magnetic solid-phase extraction and HPLC-UV for simultaneous determination of four phthalate esters in plastic bottled juice.

A magnetic o-hydroxyazobenzene (M-HAzo) porous organic polymer was facilely prepared by a green azo coupling reaction in aqueous solution. The prepared M-HAzo was applied as a new adsorbent for the first time to pre-concentrate phthalate esters (PAEs) from plastic bottled juice, followed by their determination with high performance liquid chromatography-ultraviolet detection. The effects of various parameters, i.e., the mass ratio of the Fe3O4@SiO2 to HAzo, extraction time, ionic strength, pH of the sample, desorption conditions were optimized. Under the optimized conditions, the M-HAzo based method exhibited good performance in terms of linear range (0.3-50.0 µg L-1), detection limit (0.08-0.50 µg L-1), accuracy (recovery of 78.0-115.0%) and repeatability (relative standard deviation of 2.9-7.8%). This work provides a sensitive method for analysis of PAEs at trace levels in drinks, which is featured with high sensitivity, simple operation and environmentally-friendly merit and will have a promising potential in analysis of other organic pollutants.

[Necrostatin-1 promotes locomotor recovery after spinal cord injury through inhibiting apoptosis and M1 polarization of microglia/macrophage in mice].

Objective To investigate the effect of necrostatin-1 on locomotor recovery after spinal cord injury (SCI) in mice, and to explore the role of apoptosis and M1 type-microglia/macrophage-mediated pro-inflammation in the protective effect. Methods Male C57BL/6 mice were randomly divided into four groups: control group, necrostatin-1 group, SCI model group, necrostatin-1-treated group after SCI, with 20 mice in each. For SCI model group, mice were anesthetized with 10 g/L pentobarbital sodium with a dose of 8 mL/kg. After skin disinfection, T8 laminectomy was performed under operating microscope, and the T8 spinal cord was clearly revealed. The injury model was established with a device designed by our own with the parameter at 0.2 mm-width for 20 seconds. Manual urination was performed once a day. For necrostatin-1-treated group after SCI, 7.8 mg/kg of necrostatin-1 was intravenously administrated at the 1, 2, and 3 days after SCI. For necrostatin-1 group, necrostatin-1 was intravenously injected for three days. Basso Mouse Scale(BMS) score and standardized rump-height index were used to evaluate locomotor function at 1-, 3-, 5-, 7-, 10- and 14-day after injury. To observe cell apoptosis in injured cord, TUNEL staining was performed at 1-, 3-, 7-, and 14-day after injury. Western blot and immunohistochemical staining were performed to detect the expression of inducible nitric oxide synthase (iNOS), a classical marker of M1 type microglia/macrophage. Real time quantitative PCR was used to detect mRNA levels of TNF-α, interleukin-1ß (IL-1ß), IL-18, IL-4, IL-5, and IL-10. Results Necrostatin-1 significantly promoted the locomotor recovery in mice after SCI, reduced cell apoptosis around the SCI area; decreased the protein expression of M1 type microglia/macrophage marker iNOS and the number of iNOS-positive microglia/macrophage, and down-regulated the transcription levels of pro-inflammatory cytokines TNF-α, IL-18, and IL-1ß, while promoting the transcription of anti-inflammatory cytokines IL-4, IL-5, and IL-10. Conclusion Necrostatin-1 significantly promotes locomotor function recovery after SCI in mice by reducing the number of apoptotic cells and inhibiting M1 microglia/macrophages-mediated pro-inflammatory factors.

Necroptotic astrocytes induced neuronal apoptosis partially through EVs-derived pro-BDNF.

Our previous study showed that neuronal apoptosis was significantly increased upon treatment of conditioned medium (CM) from necroptotic astrocytes (NAS), leaving the underlying mechanism unclear. Considering the nutritive and supportive roles of astrocytes, we first examined the neurotrophic phenotype of necroptotic astrocytes with focus on glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), two important neurotrophic factors, and it was unexpectedly found that the expression of GDNF and BDNF were up-regulated in necroptotic astrocytes in vitro. A question was raised as to whether the functional secreted forms of neurotrophic factors were increased. Considering that extracellular vesicles (EVs) were carriers of secreted substances and their roles in cellular interaction, we isolated EVs from astrocytes and found EVs from normal and necroptotic astrocytes (EVs-NAS) had characteristics of exosomes. We then examined GDNF and BDNF in EVs-NAS, and BDNF was interestingly found as an immature form of pro-BDNF. The expression of pro-BDNF was found to be increased in EVs-NAS, and EVs-NAS had a negative effect on neuronal survival. To verify that whether pro-BDNF was involved in the detrimental effect of EVs-NAS, anti-pro-BDNF antibody was applied, and we found that neuronal apoptosis-induced by EVs-NAS could be significantly attenuated by blocking pro-BDNF, which suggested that necroptotic astrocytes induced neuronal apoptosis partially through EVs-derived pro-BDNF. The data expand our understanding in neurotrophic phenotype of necroptotic astrocytes, and may provide us new strategies targeting on EVs-NAS in treatment of neurological diseases.

Indoleamine 2, 3-dioxygenase 1 aggravates acetaminophen-induced acute liver failure by triggering excess nitroxidative stress and iron accumulation.

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.

Caveolin-1 protects against DSS-induced colitis through inhibiting intestinal nitrosative stress and mucosal barrier damage in mice.

Caveolin-1 (Cav-1) is a multifunctional protein and critical for the production of nitric oxide (NO) in intestinal physiological and pathological conditions, but its role in the inflammatory bowel disease(IBD) are still controversial. In this study we tested the hypothesis that Cav-1 could be an important cellular defense against IBD through inhibiting nitrosative stress and mucosal barrier damage. Male wild-type mice and Cav-1 knockout (Cav-1-/-) mice were subjected to 3% dextran sodium sulfate(DSS) for 7d to establish the experimental colitis model. A representative iNOS inhibitor (1400 W) was adopted to suppress the activity of iNOS in parallel group. Body weight and disease activity index were monitored. The colon tissues were evaluated through histological analysis. We found Cav-1 was down-regulated in the colon tissue and accompanied with the increase of iNOS and NO levels after DSS administration. Cav-1-/- mice were greatly increased susceptibility to DSS-induced colitis with the more weight loss and higher disease score than WT mice. Ablation of Cav-1gene significantly resulted in RNS overproduction, tight junctions impaired and inflammation elevated, which aggravated the severity of the intestinal damages. Furthermore, pharmacologic inhibition of iNOS by 1400 W significantly attenuated DSS-induced colitis in both WT and Cav-1-/- groups. Our results revealed an important role of Cav-1 in preventing intestinal nitrosative stress and mucosal barrier damage in the development of DSS-induced colitis.

Caveolin-1 dictates ferroptosis in the execution of acute immune-mediated hepatic damage by attenuating nitrogen stress.

Ferroptosis is a new regulated cells death manner defined as results of iron-dependent accumulation of lipid peroxidation. However, the specific mechanisms of regulating ferroptosis remain unclear. In our present study, we demonstrated that Caveolin-1 (Cav-1) played a central role in protecting hepatocytes against ferroptosis in autoimmunity-mediated hepatitis (AIH). The down-regulated Cav-1 in liver tissues, accompanied by ferroptotic events and RNS production, were contributed to the outcome of ConA-induced hepatic damage, which were rescued by ferrostatin-1 (an inhibitor of ferroptosis) in vivo and in vitro. Additionally, Cav-1 deficiency aggravated ConA-induced hepatocellular death and ferroptosis associated with excessive nitrogen stress response. Short hairpin RNA of Cav-1 in hepatocytes promoted ferroptosis and nitrative stress in response to erastin in vitro, which was ameliorated by Cav-1 over-expression. Meanwhile, administration of the iNOS inhibitor (1400W) or ONOO- scavenger (Fe-TMPyP), diminished reactive nitrogen species (RNS), remarkably reduced hepatocytes ferroptosis and attenuated ConA-induced liver damage. Furthermore, immune inhibition by gadolinium chloride (GdCl3), a well-known Kupffer cell depletor, elevated hepatic Cav-1 but inhibited ferroptosis and nitrative stress under ConA exposure. In conclusion, these data revealed a novel molecular mechanism of ferroptosis with the Cav-1 regulation was essential for pathogenesis of ConA-induced hepatitis. Downstream of Cav-1, RNS-mediated ferroptosis was a pivotal step that drives the execution of acute immune-mediated hepatic damage.

EPLIN regulates actin dynamics by cross-linking and stabilizing filaments.

Epithelial protein lost in neoplasm (EPLIN) is a cytoskeleton-associated protein encoded by a gene that is down-regulated in transformed cells. EPLIN increases the number and size of actin stress fibers and inhibits membrane ruffling induced by Rac. EPLIN has at least two actin binding sites. Purified recombinant EPLIN inhibits actin filament depolymerization and cross-links filaments in bundles. EPLIN does not affect the kinetics of spontaneous actin polymerization or elongation at the barbed end, but inhibits branching nucleation of actin filaments by Arp2/3 complex. Side binding activity may stabilize filaments and account for the inhibition of nucleation mediated by Arp2/3 complex. We propose that EPLIN promotes the formation of stable actin filament structures such as stress fibers at the expense of more dynamic actin filament structures such as membrane ruffles. Reduced expression of EPLIN may contribute to the motility of invasive tumor cells.

Green synthesis of o-hydroxyazobenzene porous organic polymer for efficient adsorption of aromatic compounds.

This work presents a simple and eco-friendly synthetic approach to fabricate a novel o-hydroxyazobenzene porous organic polymer (HAzo-POP) by diazo-coupling of 2,6-diaminoanthraquinone with m-trihydroxybenzene in aqueous solution. The prepared HAzo-POP possesses good stability and high adsorption capability towards aromatic organic pollutants due to its porous nature, highly conjugated structure and strong hydrogen bonding ability. The HAzo-POP was successfully used for the solid-phase extraction of phenylurea herbicides from six real samples prior to high performance liquid chromatography with ultraviolet detection. The analytical method showed good linearity in the range of 0.5-160.0 ng g-1 for celery, lettuce and tomato samples, and 0.4-160.0 ng mL-1 for milk, soybean milk and juice samples, with low limits of detection in the range from 0.05 to 0.30 ng g-1 (or mL-1). The HAzo-POP has a promising application potential for the adsorption of more aromatic organic compounds.

Protection of a polysaccharide from Salvia miltiorrhiza, a Chinese medicinal herb, against immunological liver injury in mice.

This study was designed to evaluate the hepatoprotective effects of S. miltiorrhiza polysaccharides (SMPS) in immunological liver injury induced by Bacille-Calmette-Guerin (BCG) and lipopolysaccharide (LPS) in mice. SMPS effectively improved the liver index, spleen index and thymus index, reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and nitric oxide, and restored liver homogenate contents of tumor necrosis factor-alpha and interleukin-1beta. The histopathological analysis suggested that SMPS reduced the degree of liver injury. The results suggest that SMPS play a protective role against immunological liver injury, which may have important implications for our understanding on the immunoregulatory mechanisms of polysaccharides.

[Clinicopathologic characteristics and outcomes of IgA nephropathy in elder patients].

OBJECTIVE: To investigate the clinical, pathological characteristics and outcomes of IgA nephropathy in the elderly. METHODS: Seventy patients over age 60 with IgA nephropathy were studied and compared with 82 patients under 60 years in the clinical and pathological features as well as the outcomes. RESULTS: Compared with non-elderly group, elder group patients had higher blood pressure [systolic pressure (142.0+/-20.4) mmHg vs (124.2+/-16.9) mmHg (1mmHg=0.133 kPa), diastolic pressure (83.1+/-11.8) mmHg vs (78.9+/-12.3) mmHg], serum creatinine [(172.7+/-125.8) micromol/L vs (94.4+/-42.5) micromol/L], serum cholesterol[(5.7+/-1.6) mmol/L vs (5.1+/-1.6) mmol/L], 24 hj urinary protein excretion rate [(3.4+/-2.9) g/d vs (1.8+/-2.0) g/d], and the incidence of CKD stages 3-5(64.0% vs 14.6%)(P<0.05). No significant differences were seen in the disease courses, rate of gross hematuria, serum triglyceride and serum IgA level between two groups(P>0.05).Renal pathological investigation showed the chronic lesions were dominated in elder group. There was significant difference in portion of glomerular sclerosis [(19.7+/-20.1)% vs (13.4+/-17.8)%], renal tubule atrophy (>1 score,34.2% vs 25.6%), interstitial fibrosis (>1,score 34.2% vs 18.2%), and arteriolosclerosis (>2 score,20.0% vs 8.5%) between two groups (P<0.05). However, there were no significant difference in proportion of mesangial proliferation, crescent and interstitial inflammatory cell infiltration (P>0.05). After a mean post-biopsy follow-up of (34.6+/-33.3) months, the 3-year and the 5-year renal survival rates for elder group were 74.6% and 62.2%, respectively, which were lower than those of non-elder group (100% and 92.9%, P=0.002). CONCLUSION: Elder patients with IgA nephropathy were more likely to suffer from hypertension, hyperlipidemia, renal insufficiency and chronic pathologic lesions, which might be the risk factors for the patient's unfavorable prognosis.

[Apoptosis and activity changes of telomerase induced by essential oil from pine needles in HepG2 cell line].

OBJECTIVE: To study the effects of essential oil extracted from pine needles on HepG2 cell line. METHODS: HepG2 cells were treated with essential oil extracted from pine needles. Cell growth rate was determined with MTF assay, cell morphologic changes were examined under transmission electromicroscope and HE straining. Flow cytometry was used to exmine apoptotic cells. Bcl-2 gene expression was determined by flow cytometry and telomerase activity by TRAP assay. RESULTS: Essential oils from pine needles could not only repress the growth of HepG2 cells significantly, but also induce apoptosis to them. Both dose-effect and time-effect relationship could be confirmed. Typical morphology changes of apoptosis such as nuclear enrichment and karyorrhexis were observed through transmission electromicroscope and HE straining. Telomerase activity was down regulated in the essential oil extracted from pine needles induced apoptotic cells. The expression of bcl-2 gene was suppressed after the essential oil from pine needles treatement. CONCLUSION: The essential oil extracted from pine needles can inhibit cell growth of HepG2 cell line and induce apoptosis, which may associate with inhibition of telomerase activity and bcl-2 may be involved in the regulation of telomerase activity.