A new strategy to stabilize the heavy metals in carbonized MSWI-fly ash using an acid-resistant oligomeric dithiocarbamate chelator.

Fly ash (FA) derived from municipal solid waste incineration (MSWI) requires safe handling before landfilling due to its extremely high salt content and the risk of leaching heavy metals (HMs) under acidic conditions. Herein, aimed at improving the acid stability of dithiocarbamates, a cost-effective oligomeric dithiocarbamate (ODTC) was developed to stabilize HMs from carbonated MSWI-FA. Spiking of 3.6 wt% ODTC reduced the HM leaching below landfill standards in China, even across the pH range of 2.0-13.0 or 8-week exposure to the natural environment. Stabilization decreased the acid-soluble/exchangeable fractions of Cd, Pb, and Zn from 22.2%, 4.49%, and 21.9% to 0.14%, 0.11%, and 12.2%, respectively, resulting in safe levels for Pb and Cd with risk assessments. Compared to DDTC and SDD, ODTC exhibited higher stability under acidic conditions after chelation with the HMs, minimized the risk of HM leaching, and significantly reduced stabilization costs. In-depth studies proved that the stabilization mechanism involved the ability of ODTC to chelate HMs strongly and form acid-resistant ODTC-HM complexes, agglomeration of the MSWI-FA grains to encapsulate the ODTC-HM complexes, transformations of the HMs from acid-soluble species to stable oxidizable and residual species, and specifically ODTC reducing high-valent Pb to more stable Pb(II) species.

Gut-licensed ß7+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma.

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.

Enhancing sulfate reduction and hydrogen sulfide removal through gas stripping in the acidogenesis phase of a two-phase anaerobic process.

This study aims at evaluating two-phase and single-phase reactors for treating sulfate wastewater with low COD/SO42- ratios. Additionally, a new process of gas stripping in an acidogenesis phase is proposed to reduce hydrogen sulfide (H2S) inhibition and enhance biomethanation. The two-phase performed better than the single-phase in terms of COD removal, CH4 production and H2S resistance. After 30 days of stripping, the COD and sulfate degradation rates increased from 85.16% to 91.09% and from 49.39% to 63.07% in the two-phase, respectively. In contrast, without stripping, they were from 79.21% to 64.37% and from 50.26% to 53.15% in the single-phase, respectively. The microbial biodiversity was augmented via stripping, including norank_f__Spirochaetaceae, Petrimonas, Desulfurella and Blvii28_wastewater-sludge_group. Stripping operation enhanced the dissimilatory sulfate reduction, amino acid metabolism and possibly sulfate-dependent anaerobic ammonia oxidation (S-ANAMMOX). This study provides a promising strategy to improve sulfate reduction and reduce H2S inhibition under a low COD/SO42- ratio.

Prognostic Significance of Iron Metabolism Related Genes in Human Lung Adenocarcinoma.

Background: Iron metabolism related genes participate in cell proliferation, cell growth, and redox cycling in multiple cancers. Limited studies have revealed the roles and clinical significance of iron metabolism in the pathogenesis and prognosis of lung cancer. Methods: A total of 119 iron metabolism related genes were extracted from MSigDB database and their prognostic values were determined in The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) dataset and the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. Immunohistochemistry technique and correlations with immune cell infiltration, gene mutation and drug resistance were used to identify the potential and underlying mechanisms of STEAP1 and STEAP2 as prognostic biomarkers of LUAD. Results: The expression of STEAP1 and STEAP2 are negatively associated with the prognosis of LUAD patients both at the mRNA and protein level. The expression of STEAP1 and STEAP2 was not only negatively correlated with the trafficking degree of CD4+ T immune cells and positively related to most immune cells' trafficking degree, but also significantly associated with gene mutation status, particularly with mutations on TP53 and STK11. Four types of drug resistance showed significant correlation with the expression level of STEAP1 while 13 types of drug resistance were associated with the expression level of STEAP2. Conclusion: Multiple iron metabolism related genes including STEAP1 and STEAP2 are significantly associated with the prognosis of LUAD patients. STEAP1 and STEAP2 might affect the prognosis of LUAD patients partially through immune cell infiltration, gene mutation and drug resistance, which indicated they were independent prognostic factors for LUAD patients.

Prevalence of depressive symptoms and correlates among individuals who self-reported SARS-CoV-2 infection after optimizing the COVID-19 response in China.

Background: The burden of depression symptoms has increased among individuals infected with SARS-CoV-2 during COVID-19 pandemic. However, the prevalence and associated factors of depressive symptoms among individuals infected with SARS-CoV-2 remain uncertain after optimizing the COVID-19 response in China. Methods: An online cross-sectional survey was conducted among the public from January 6 to 30, 2023, using a convenience sampling method. Sociodemographic and COVID-19 pandemic-related factors were collected. The depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was performed to explore the associated factors with depressive symptoms. Results: A total of 2,726 participants completed the survey. The prevalence of depression symptoms was 35.3%. About 58% of the participants reported experiencing insufficient drug supply. More than 40% of participants reported that they had missed healthcare appointments or delayed treatment. One-third of participants responded experiencing a shortage of healthcare staff and a long waiting time during medical treatment. Logistic regression analysis revealed several factors that were associated with depression symptoms, including sleep difficulties (OR, 2.84; 95% CI, 2.34-3.44), chronic diseases (OR, 2.15; 95% CI, 1.64-2.82), inpatient treatment for COVID-19 (OR, 3.24; 95% CI, 2.19-4.77), with COVID-19 symptoms more than 13 days (OR, 1.30, 95% CI 1.04-1.63), re-infection with SARS-CoV-2 (OR, 1.52; 95% CI, 1.07-2.15), and the increased in demand for healthcare services (OR, 1.32; 95% CI, 1.08-1.61). Conclusion: This study reveals a moderate prevalence of depression symptoms among individuals infected with SARS-CoV-2. The findings underscore the importance of continued focus on depressive symptoms among vulnerable individuals, including those with sleeping difficulties, chronic diseases, and inpatient treatment for COVID-19. It is necessary to provide mental health services and psychological interventions for these vulnerable groups during the COVID-19 epidemic.

Structure-based analysis and rational design of human peroxiredoxin-1's C-terminus-derived peptides to target sulfiredoxin-1 in pancreatic cancer.

Human peroxiredoxin (PRX) family of antioxidant enzymes reduces hydrogen peroxide and alkyl hydroperoxide involved in the redox signaling, among which the widely documented PRX1 is a versatile molecule regulating cell growth, differentiation and apoptosis, and has been implicated in the tumorigensis of pancreatic cancer. In this study, we systematically examined the complex crystal structure of PRX1 with its cognate interacting partner sulfiredoxin-1 (SRX1) at molecular level, and found that the PRX1-SRX1 association is a typical peptide-mediated protein-protein interaction, where a 18-mer C-terminal tail (CTT) segment of PRX1 was identified to be primarily responsible for the interaction, which contributes ~80% and ~ 55% to the total binding potency of SRX1 to PRX1 monomer and homodimer, respectively. We also demonstrated that the SRX1 exhibits a strong global selectivity for PRX1 CTT tail over other PRX family proteins. Next, the intermolecular interaction between PRX1 CTT tail and SRX1 was investigated at structural, energetic and dynamic levels, from which a 9-mer core region of PRX1 CTT tail was defined as the SRX1-binding hotspot. Biophysical assays substantiated that the CTT and CTTc peptides (out of PRX1 protein context) can bind in an independent manner and possess a close affinity to SRX1. Based on the CTTc sketch a computational combinatorial library consisting of 216 designed peptide derivatives was rationally generated, from which the top-5 hits were found to have comparable affinity with CTT peptide and improved affinity relative to CTTc peptide. They can be used as structurally reduced lead molecular entities to further develop new peptidic agents for therapeutic purpose to disrupt the native PRX1-SRX1 interaction by competing with PRX1 CTT tail for the peptide-binding pocket of SRX1.

Identification and Characterization of Extrachromosomal Circular DNA in Plasma of Lung Adenocarcinoma Patients.

Background: Chromosome is the basic framework for eukaryotic cells to store genetic information, but certain genes exist in circulation, such as extrachromosomal circular DNA (eccDNA). The unique genetic characteristics and structure of eccDNA provide a new vision on the early diagnosis of cancer; however, whether eccDNA contributes to the early diagnosis and progression of lung cancer remains unclear. Methods: We performed next-generation sequencing (NGS) analysis of eccDNA from the plasma of 6 lung adenocarcinoma (LUAD) patients. The data of plasma eccDNA of healthy people were obtained from public available database. We compared size distribution, chromosome origin, formation and expression patterns of eccDNA between LUAD patients and those of 6 healthy people and 4 healthy gravidas. Results: A total number of 716,059 eccDNA ranging from 22 bp to 3,297,519 bp were detected with an average size less than 800bp and distinctive bimodality in size around 191 bp and 320 bp. After comparison of eccDNA abundance in each sequencing sample, nine eccDNA were ranked on top with higher frequency in lung adenocarcinoma patients than healthy people. Among them, four eccDNA (DOCK1, PPIC, TBC1D16, and RP11-370A5.1) were uniquely expressed in lung adenocarcinoma patients, which may serve as potential biomarkers for early diagnosis LUAD. Conclusion: Cancer-specific eccDNA was presented in LUAD compared to normal people, which might serve as a promising biomarker in LUAD.

Alleviation of Reverse Salt Leakage across Nanofiber Supported Thin-Film Composite Forward Osmosis Membrane via Heat-Curing in Hot Water.

Electrospun nanofiber with interconnected porous structure has been studied as a promising support layer of polyamide (PA) thin-film composite (TFC) forward osmosis (FO) membrane. However, its rough surface with irregular pores is prone to the formation of a defective PA active layer after interfacial polymerization, which shows high reverse salt leakage in FO desalination. Heat-curing is beneficial for crosslinking and stabilization of the PA layer. In this work, a nanofiber-supported PA TFC membrane was conceived to be cured on a hot water surface with preserved phase interface for potential "defect repair", which could be realized by supplementary interfacial polymerization of residual monomers during heat-curing. The resultant hot-water-curing FO membrane with a more uniform superhydrophilic and highly crosslinked PA layer exhibited much lower reverse salt flux (FO: 0.3 gMH, PRO: 0.8 gMH) than that of oven-curing FO membrane (FO: 2.3 gMH, PRO: 2.2 gMH) and achieved ∼4 times higher separation efficiency. It showed superior stability owing to mitigated reverse salt leakage and osmotic pressure loss, with its water flux decline lower than a quarter that of the oven-curing membrane. This study could provide new insight into the fine-tuning of nanofiber-supported TFC FO membrane for high-quality desalination via a proper selection of heat-curing methods.

Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis.

Carbamoyl phosphate synthetase 1 (CPS1), which is the antigen for the hepatocyte paraffin 1 antibody, exhibits focal immunoreactivity in adenocarcinoma from the gastrointestinal tract, but its expression profiles and roles in gastric cancer (GC) remain largely unknown. The present study aimed to determine the expression pattern and prognostic value of CPS1 in Correa's cascade using tissues from 32 patients with chronic atrophic gastritis with intestinal metaplasia (IM), 62 patients with low- or high-grade intraepithelial neoplasia (IN) and 401 patients with GC. The expression of CPS1 was diffuse and strongly positive in 32 cases (100%) of IM of the glandular epithelium, and gradually downregulated in Correa's cascade, with a strongly positive ratio of 21 (70%) in low-grade IN and 4 (12.5%) in high-grade IN. The levels of CPS1 expression were significantly higher in diffuse-type GC, with 37 (26%) cases strongly positive for CPS1, compared with 14 (8%) in intestinal-type and 11 (13%) cases in mixed-type GC. In intestinal-type GC, CPS1 expression was completely lost in 107 (62%) of cases, which was associated with an advanced Tumor-Node-Metastasis stage (P=0.031) and depth of invasion (P=0.037). Kaplan-Meier analysis suggested that low CPS1 expression levels were independently associated with a short overall survival (OS) time in the three types of GC (P<0.001 in intestinal-type, P=0.003 in diffuse-type and P=0.018 in mixed-type GC). Furthermore, low levels of CPS1 mRNA and high methylation levels in the CPS1 promoter were associated with a short OS time in patients with GC. These results suggested that the expression of CPS1 was progressively downregulated in Correa's cascade, and that CPS1 may serve as a prognostic marker for patients with GC, regardless of tumor type.

A survey of clinical and laboratory characteristics of dengue fever epidemic from 2014 to 2018 in Guangzhou, China.

BACKGROUND: In 2014, a serious dengue outbreak occurred in Guangzhou, South China. In this study, the clinical and laboratory characteristics of dengue fever (DF) group and other febrile illnesses (OFI) group in Guangzhou were described. METHODS: Clinical and laboratory data collected by studying 1,792 patients from Nanfang Hospital, Southern Medical University during 2014 and 2018. Laboratory data was analyzed by SPSS 22.0 statistical software including Full blood counts (SYSMEX XE-5000), Laboratory Biochemical tests (Roche Cobas 8000), Dengue virus RNA (RT-PCR-Fluorescence Probing) and Dengue IgG/IgM Antibody (Colloidal Gold), Dengue Virus NS1 (ELISA). RESULTS: In the DF group and OFI group, gender ratios were 1.08:1 (male/female, P>0.05) and 1.45:1 (male/female, P<0.05). Adults aged 25-34 years old (29.4%) with the main peak appeared in the DF group, and the same main peak appeared in the OFI group: 25-34 years old (25.13%). Patients were from Medical emergency (41.2% DF group, 29.4% OFI group). The distribution of fever days before treatment was mainly focused within 5 days, with a main peak in the 2 fever days before treatment (24.6%) in the DF group and the main peak in 1 fever day before treatment (46.9%) in OFI group. The major symptoms of the DF group were presented with were fever (100%), myalgia (34.77%), pharyngeal hyperemia (31.33%), headache (25.65%), adenoids (19.62%), and rash (13.25%). In the OFI group, Pharyngeal hyperemia was the most common clinical symptom, accounting for 27.24%, and the next symptom was adenoids (21.26%). The sensitivity and specificity of DV RNA were 61.54%, 100%, respectively, compared to the DF Nonstructural protein 1 (NS1). Dengue virus (DENV) Immunoglobulin M (IgM) IgM in both groups was statistically significant, with DENV-IgM in the DF group were stronger (Z=-7.863, P<0.001), and DENV immunoglobulin G (IgG) were no statistically significant (Z=-1.212, P=0.226). In DF group, 37.14% of serum samples had elevated Alanine transaminase (ALT) levels, 76.85% of them had elevated aspartate aminotransferase (AST) levels, 32.08% of them had elevated creatine kinase (CK) levels, and 2.67% of them had elevated C-reaction protein (CRP) levels, compared with 13.51% of them had elevated ALT levels, 30.65% of them had elevated AST levels, 6.06% of them had elevated CK levels and 69.35% of them had elevated CRP levels of the OFI patients. The prominent manifestations were thrombocytopenia (occurring in 28.07% of the DF group, compared to 5.18% of OFI group) and leucopenia (occurring in 43.27% of DF group and 3.63% of OFI group). The DF incidence of all fever cases was 49.0% within three months in 2014, compared with 1.4% in 2015, 0% in 2016, 0.9% in 2017 and 6.4% in 2018 (P<0.001). DF and OFI can occur in any age and sex. DF occurred in the young and the old, OFI occurred in children and youth. The clinical symptoms of myalgia, headache, rash, weak, Chills, follicular hyperplasia in both groups were statistically significant (P<0.001). CONCLUSIONS: IgM can be easily recognized for early diagnoses, DENV-RNA had lower sensitivity and higher specificity, and DF NS1 enzyme-linked immunosorbent assay (ELISA) has a higher sensitive and specificity. DF is a serious public health problem and an emerging continuous threat in Guangzhou. In high-prevalence areas, effective epidemic monitoring and prevention measures need to be undertaken. After the unprecedented outbreak in 2014, on account of the government and citizen paying more attention to the DF epidemic, the cases of DF were decreased significantly from 2015 to 2018.

Identification of anti-CD16a single domain antibodies and their application in bispecific antibodies.

CD16a (FcγRIIIa) mediates the antibody dependent cellular cytotoxicity (ADCC) and is important for anti-tumor activities of many therapeutic antibodies. Bispecific antibody targeting natural killer (NK) cells has been studied for cancer therapy. In this work, anti-CD16a single-domain antibodies were identified from hCD16a immunized camel. Bispecific antibodies are then constructed by fusing these single domain antibodies with an anti-CEA single domain antibody. These bispecific antibodies can recruite NK cells to kill CEA-positive tumor cells, and inhibit tumor growth in vivo, suggesting that these anti-CD16a single domain antibodies are powerful tools to engaging NK cells for cancer therapy.

Flexible and porous TiO2/SiO2/carbon composite electrospun nanofiber mat with enhanced interfacial charge separation for photocatalytic degradation of organic pollutants in water.

Semiconductor photocatalysis has long been considered as a promising approach for remediation of polluted water. However, the high recombination rate of electrons and holes, as well as a low reaction rate, have impeded its large-scale applications. Therefore, it is of great importance to develop appropriate photocatalysts for promoting its practical application. In this study, a novel TiO2/SiO2/carbon electrospun nanofiber mat (TSC NFM) with flexibility and porous hierarchy has been successfully designed and fabricated by a facile method of electrospinning and carbonization. Characterization results show that the TSC NFM consists of closely-packed and well-distributed anatase (TiO2) nanocrystals, amorphous SiO2 nanoparticles, and carbon with interconnected meso- and macro-pores. The photocatalytic performance of the TSC NFM was evaluated by degrading rhodamine B and 4-nitrophenol in batch systems. The results show that TSC NFM exhibits a higher photocatalytic activity than TiO2/SiO2 nanofiber mat, which does not contain carbon. The enhanced performance of the TSC NFM can be attributed to the improved adsorption capacity toward the organic pollutants due to the presence of carbon and to the enhanced interfacial charge separation between TiO2 nanoparticles and carbon. Besides, the as-prepared TSC NFM displays good stability and reusability. Notably, the flexible TSC NFM can be used in a continuous-flow reactor to efficiently treat wastewater. Our work provides new insights into the fabrication of carbon-based inorganic nanofiber mats, which have great potential in water treatment.

Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities.

Patients with Human epidermal growth factor receptor type 2 (Her2) overexpression are associated with aggressive tumor growth and poor clinical outcomes. Bispecific antibodies targeting Her2 have recently exhibited potent effects on Her2 signal inhibition. In this study, a novel biparatopic anti-Her2 bispecific antibody (Bp-Bs) was constructed by linking a single anti-CD3 Fab with two different anti-Her2 single-domain antibodies targeting non-overlapping epitopes of Her2. The Bp-Bs demonstrated strong binding on Her2-positive cells and potent cytotoxicity on Her2-positive tumor cells, even Her2-low expression cells, suggesting that biparatopic bispecific antibodies may have improved therapeutic benefits on broad Her2 patient populations.

Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model.

To investigate the neuroprotective effects of the mitochondria-targeted antioxidant Szeto-Schiller peptide 31 (SS-31) in a rat experimental glaucoma model, SS-31 was intraperitoneally (IP) injected into Sprague-Dawley rats, followed by intracameral injection of polystyrene microspheres to induce elevated intraocular pressure (IOP). After 6 weeks, electroretinography (ERG) and flash visual-evoked potentials (F-VEPs) were recorded to assess retinal function. Hematoxylin-eosin staining was performed on retinal cross-sections to measure ganglion cell complex (GCC) thickness. Apoptotic retinal cells were assessed by TUNEL staining. Brn3a-positive retinal ganglion cells (RGCs) were counted in retinal flat mounts via immunofluorescence. The retinal total SOD, SOD2, and MDA expression levels were assessed in retinal tissue homogenates. The cyt c, Bax, and Bcl-2 protein levels in rat retinas were detected by western blot analysis. Bax and Bcl-2 expressions were also evaluated using immunohistochemistry in paraffinized sections. Our results showed that the rats that received microsphere injection developed elevated IOP. SS-31 ameliorated the reductions in the a- and b-wave amplitudes on ERG and the F-VEP amplitude in glaucomatous eyes. GCC thickness was preserved, TUNEL-positive cells were decreased in the retina, and Brn3a-positive RGCs were increased in the SS-31-treated glaucoma group compared with those in the non-treated glaucoma group. SS-31 significantly reduced MDA levels and increased SOD2 levels after glaucoma induction. Significant suppression of cyt c release, upregulation of Bcl-2, and downregulation of Bax were observed following SS-31 administration. In summary, SS-31 exerts neuroprotective effects in this experimental glaucoma model by inhibiting mitochondrial dysfunction and therefore represents a promising therapeutic agent for glaucoma.

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity.

This protocol describes the construction and functional studies of a bispecific antibody (bsAb), GPC3-S-Fab. bsAbs can recognize two different epitopes through their two different arms. bsAbs have been actively studied for their ability to directly recruit immune cells to kill tumor cells. Currently, the majority of bsAbs are produced in the form of recombinant proteins, either as Fc-containing bsAbs or as smaller bsAb derivatives without the Fc region. In this study, GPC3-S-Fab, an antibody fragment (Fab) based bispecific antibody, was designed by linking the Fab of anti-GPC3 antibody GC33 with an anti-CD16 single domain antibody. The GPC3-S-Fab can be expressed in Escherichia coli and purified by two affinity chromatographies. The purified GPC3-S-Fab can specifically bind to and kill GPC3 positive liver cancer cells by recruiting natural killer cells, suggesting a potential application of GPC3-S-Fab in liver cancer therapy.

A Single Domain-Based Anti-Her2 Antibody Has Potent Antitumor Activities.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

Expression of vimentin and glial fibrillary acidic protein in central nervous system development of rats.

OBJECTIVE: To investigate the distribution and contents of vimentin (Vim) and glial fibrillary acidic protein (GFAP) immunoreactivities in the central nervous system (CNS) of normal newborn, adult and aged rats. METHODS: In this study, thirty healthy and normal Sprague-Dawley rats were simply classified into three groups: Newborn (7 days aged), adult (5 months aged) and aged (24 months aged) rats. Brains and spinal cord were dissected and cut into frozen sections. The expression of Vim and GFAP in CNS were detected by confocal immunofluorescence. RESULTS: In each group, Vim was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was highest in neuron-like cell of newborn rats, while Vim was mainly expressed in cell bodies in adult and aged rats. GFAP was expressed in all the regions of CNS including the hippocampal, cerebral cortex, the third ventricle and spinal cord, and the expression was in astrocytes of aged rats. In the third ventricle, Vim was detected in all groups, and only observed in neuron-like cells of newborn. Meanwhile, the GFAP expression showed no significant differences between adult and aged rats in this region. The co-localization of Vim and GFAP were mainly observed in hippocampus and cerebral cortex of newborn, but this co-localization was found in the third ventricle of the rats in all groups. CONCLUSION: Our data demonstrate for the first time that the expression of Vim and GFAP in the rat's CNS during development. This data may provide a foundation for the further mechanistic studies of these two main intermediate filaments during development of CNS.

microRNA-352 regulates collateral vessel growth induced by elevated fluid shear stress in the rat hind limb.

Although collateral vessel growth is distinctly enhanced by elevated fluid shear stress (FSS), the underlying regulatory mechanism of this process remains incompletely understood. Recent studies have shown that microRNAs (miRNAs) play a pivotal role in vascular development, homeostasis and a variety of diseases. Therefore, this study was designed to identify miRNAs involved in elevated FSS-induced collateral vessel growth in rat hind limbs. A side-to-side arteriovenous (AV) shunt was created between the distal stump of one of the bilaterally occluded femoral arteries and the accompanying vein. The miRNA array profile showed 94 differentially expressed miRNAs in FSS-stressed collaterals including miRNA-352 which was down-regulated. Infusion of antagomir-352 increased the number and proliferation of collateral vessels and promoted collateral flow restoration in a model of rat hind limb ligation. In cell culture studies, the miR-352 inhibitor increased endothelial proliferation, migration and tube formation. In addition, antagomir-352 up-regulated the expression of insulin-like growth factor II receptor (IGF2R), which may play a part in the complex pathway leading to arterial growth. We conclude that enhanced collateral vessel growth is controlled by miRNAs, among which miR-352 is a novel candidate that negatively regulates arteriogenesis, meriting additional studies to unravel the pathways leading to improved collateral circulation.

Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo.

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.

Evaluation of AhR-agonists and AhR-agonist activity in sediments of Liaohe River protected areas, China.

A total of 9 sediment samples of Liaohe River protected areas were collected to evaluate aryl hydrocarbon receptor agonists (AhR-agonists) and AhR-agonist activity via chemical analysis and in vitro H4IIE cell bioassay. Results indicated that bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (Bio-TEQs) ranged from 89.1 to 251.1pg/g dry weight. Concentrations of 16 EPA polycyclic aromatic hydrocarbons (PAHs), 12 dioxin-like polychlorinated biphenyls (PCBs), and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) ranged from 256.8 to 560.1ng/g, 79.2 to 416.2pg/g, and 199.6 to 538.4pg/g, respectively. According to potency balance analysis, TEQchems based on PAHs, PCBs, and PCDD/Fs could contribute 16.56% to 26.11% of Bio-TEQs. This could be explained by the potential existence of unidentified AhR-agonists and the potential non-additive interactions among AhR-agonists in sediment extracts. Through the different contributions to Bio-TEQs, this study confirms that PCDD/Fs were the main pollutants that induced significantly AhR-agonist activity in sediments of Liaohe River protected areas.