Does mangrove leave falling dominate the bury of polycyclic aromatic hydrocarbons in the mangrove of China?

Mangrove wetlands are vital coastal ecosystems that can absorb and accumulate pollutants. Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that pose potential risks to ecosystems and human health. However, their source and transport fate in mangrove areas are poorly understood. This study investigates 29 PAHs pollution of water and sediment in Zhangjiangkou Mangrove Wetland, the northernmost large-scale mangrove wetland reserve in China. We examine the distribution, source, transport mechanisms and risk assessment of PAHs. The results show that the concentrations of PAHs in mangrove sediment range from 55.62 to 347.36 ng/g (DW), with 5-ring PAHs being the dominant species. While the concentrations of PAHs in surface water range from 10.61 to 46.39 ng/L, with 2-ring PAHs and alkylated PAHs being the dominant species. The PAHs concentrations in surface water and sediment of river are higher than those in mangrove area, indicating that mangrove water could receive PAHs through tidal exchange. Based on diagnostic ratios (DRs), principal component analysis (PCA), and positive matrix factorization (PMF), we infer that the leaf deposition (48.55%) could be an important pathway of PAHs in mangrove sediment except for river water transport (51.45%), while the PAHs in estuary water originate mainly from point sources such as biomass burning (50.96%) and traffic emission (49.04%). The range of toxic equivalents in surface water and sediment was 2.73-16.09 ng TEQ g-1 and 0.03-3.63 ng/L, respectively. Although the ecological risk assessment suggests that the PAHs pollution in surface water and sediment poses a low risk, we recommend more attention to the protection of the mangrove ecosystem. This study reveals that mangrove leaf falling might be a significant mechanism of PAH sequestration in the mangrove system, which deserves more attention in future research.

Study on Cavitation, Warpage Deformation, and Moisture Diffusion of Sop-8 Devices during Molding Process.

Plastic packaging has shown its advantages over ceramic packaging and metal packaging in lightweight, thin, and high-density electronic devices. In this paper, the reliability and moisture diffusion of Sop-8 (Small Out-Line Package-8) plastic packaging devices are studied, and we put forward a set of complete optimization methods. Firstly, we propose to improve the reliability of plastic packaging devices by reducing the amount of cavitation and warpage deformation. Structural and process factors were investigated in the injection molding process. An orthogonal experiment design was used to create 25 groups of simulation experiments, and Moldflow software was used to simulate the flow mode analysis. Then, the simulation results are subjected to range analysis and comprehensive weighted score analysis. Finally, different optimization methods are proposed according to different production conditions, and each optimization method can reduce cavitation or warpage by more than 9%. The moisture diffusion of the Sop-8 plastic packing devices was also investigated at the same time. It was determined that the contact surface between the lead frame and the plastic packaging material was more likely to exhibit delamination under the condition of MSL2 moisture diffusion because the humidity gradient was easily produced at the crucial points of different materials. The diffusion of moisture is related to the type of plastic packaging material and the diffusion path.

ChlOR, a GMC family oxidoreductase that evolved independently from the actinomycete, confers resistance to amphenicol antibiotics.

Overuse of the amphenicol antibiotics chloramphenicol (CHL) and thiamphenicol (TAP) poses a great threat to ecosystem safety and human health. The strain, Nocardioides sp. LMS-CY, Nocardioides sp. QY071 and Nocardioides sp. L-11A, classified as a gram-positive actinomycete, harbours a complete CHL metabolic pathway. However, the metabolic genes (clusters) involved in the entire pathway in gram-positive actinomycetes are still limited. Here, chlORLMS , chlORQY071 and chlORL-11A completely from the actinomycete Nocardioides spp. were found to act on the C1 -OH of the CHL/TAP side chain, directly converting CHL/TAP to 4-nitrobenzaldehyde (PNBD)/4-methylsulfonyl benzaldehyde (PMBD) and transforming PNBD/PMBD into 4-nitrobenzyl alcohol (PNBM)/4-methylsulfonyl phenyl methanol (PMBM). Furthermore, oxidoreductases can transform PNBM into 4-nitrobenzoate (PNBA). The oxidoreductases ChlORLMS , ChlORQY071 and ChlORL-11A were all classified as cellobiose dehydrogenases from the glucose methanol choline (GMC) family. Based on the Swiss-Prot database, ChlORQY071 exhibited a lower identity (27.12%-35.10% similarity) with the reported oxidoreductases. Enzymatic and molecular docking analyses showed that ChlORQY071 and ChlORL-11A from the two similar genomes were remarkably more effective in metabolizing CHL than ChlORLMS . Overall, the detailed resistance mechanism of CHL/TAP by actinomycete strains isolated from soil and livestock manure will provide insights into the occurrence of CHL/TAP resistance genes in the environment, resistance risk and bioremediation of CHL/TAP-contaminated environments.

Simultaneous profiling of spatial gene expression and chromatin accessibility during mouse brain development.

The brain is a complex tissue whose function relies on coordinated anatomical and molecular features. However, the molecular annotation of the spatial organization of the brain is currently insufficient. Here, we describe microfluidic indexing-based spatial assay for transposase-accessible chromatin and RNA-sequencing (MISAR-seq), a method for spatially resolved joint profiling of chromatin accessibility and gene expression. By applying MISAR-seq to the developing mouse brain, we study tissue organization and spatiotemporal regulatory logics during mouse brain development.

Combined Bioremediation of Bensulfuron-Methyl Contaminated Soils With Arbuscular Mycorrhizal Fungus and Hansschlegelia zhihuaiae S113.

Over the past decades, because of large-scale bensulfuron-methyl (BSM) application, environmental residues of BSM have massively increased, causing severe toxicity in rotation-sensitive crops. The removal of BSM from the environment has become essential. In this study, the combined bioremediation of the arbuscular mycorrhizal fungi (AMF) Rhizophagus intraradices and BSM-degrading strain Hansschlegelia zhihuaiae S113 of BSM-polluted soil was investigated. BSM degradation by S113 in the maize rhizosphere could better promote AMF infection in the roots of maize, achieving an infection rate of 86.70% on the 36th day in the AMF + S113 + BSM group. Similarly, AMF enhanced the colonization and survival of S113 in maize rhizosphere, contributing 4.65 × 105 cells/g soil on the 15th day and 3.78 × 104 cells/g soil on the 20th day to a population of colonized-S113 (based possibly on the strong root system established by promoting plant-growth AMF). Both S113 and AMF coexisted in rhizosphere soil. The BSM-degrading strain S113 could completely remove BSM at 3 mg/kg from the maize rhizosphere soil within 12 days. AMF also promoted the growth of maize seedlings. When planted in BSM-contaminated soil, maize roots had a fresh weight of 2.59 ± 0.26 g in group S113 + AMF, 2.54 ± 0.20 g in group S113 + AMF + BSM, 2.02 ± 0.16 g in group S113 + BSM, and 2.61 ± 0.25 g in the AMF group, all of which exceeded weights of the control group on the 36th day except for the S113 + BSM group. Additionally, high-throughput sequencing results indicated that simultaneous inoculation with AMF and strain S113 of BSM-polluted maize root-soil almost left the indigenous bacterial community diversity and richness in maize rhizosphere soil unaltered. This represents a major advantage of bioremediation approaches resulting from the existing vital interactions among local microorganisms and plants in the soil. These findings may provide theoretical guidance for utilizing novel joint-bioremediation technologies, and constitute an important contribution to environmental pollution bioremediation while simultaneously ensuring crop safety and yield.

Yes-associated protein gene overexpression regulated by ß-catenin promotes gastric cancer cell tumorigenesis.

BACKGROUND: Yes-associated protein (YAP) has been reported to act as a candidate human oncogene and played a critical role in the development of multiple cancer types. OBJECTIVE: We aimed to investigate the expression, function, and underlying mechanisms of YAP in gastric cancer (GC). METHODS: Expression levels of YAP in gastric tissues were tested. CCK8 assay, clonogenic assay, apoptosis assay, transwell assay, cell scratch assay and animal study were conducted to explore the function of YAP. Chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay were performed to explore the underlying mechanism. Survival analysis was carried out to reveal the relationship between YAP and clinical outcome. RESULTS: YAP was upregulated in gastric cancer tissues and correlates with poor prognosis. YAP could promote GC cells proliferation, metastatic capacity, inhibit GC cells apoptosis in vitro and in vivo. Bothß-catenin and YAP were mainly localized withi the tumor cell nuclei. ß-catenincould upregulate YAP expression by binding to the promotor region of YAP. Patients with both YAP and ß-catenin negetive expression had a better prognosis than others. CONCLUSIONS: YAP overexpression is driven by aberrant Wnt ß-catenin signalingand then contributed to the GC tumorigenesis and progression. Thus, YAP might be a potential target for GC treatment.

Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma.

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been widely reported in various cancers, including lung adenocarcinoma (LUAD). However, it is largely unknown whether SNHG7 is involved in docetaxel resistance of LUAD. In the current study, we identified the high expression of SNHG7 in docetaxel-resistant cells. Through functional assays, we determined that silencing of SNHG7 decreased IC50 value of LUAD cells to docetaxel and suppressed proliferation and autophagy in LUAD cells, and reversed M2 polarization in macrophages. Mechanistically, we uncovered that SNHG7 promoted autophagy via recruiting human antigen R (HuR) to stabilize autophagy-related genes autophagy related 5 (ATG5) and autophagy related 12 (ATG12). Moreover, exosomal SNHG7 was transmitted from docetaxel-resistant LUAD cells to parental LUAD cells and thus facilitated docetaxel resistance. Additionally, exosomal SNHG7 activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway to promote M2 polarization in macrophages via recruiting cullin 4A (CUL4A) to induce ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Taken together, we concluded that exosomal SNHG7 enhances docetaxel resistance of LUAD cells through inducing autophagy and macrophage M2 polarization. All findings in the study suggested that SNHG7 may be a promising target for relieving docetaxel resistance in LUAD.

Biofilm formed by Hansschlegelia zhihuaiae S113 on root surface mitigates the toxicity of bensulfuron-methyl residues to maize.

Bensulfuron-methyl (BSM) residues in soil threaten the rotation of BSM-sensitive crops. Microbial biofilms formed on crop roots could improve the ability of microbes to survive and protect crop roots. However, the research on biofilms with the purpose of mitigating or even eliminating BSM damage to sensitive crops is very limited. In this study, one BSM-degrading bacterium, Hansschlegelia zhihuaiae S113, colonized maize roots by forming a biofilm. Root exudates were associated with increased BSM degradation efficiency with strain S113 in rhizosphere soil relative to bulk soil, so the interactions among BSM degradation, root exudates, and biofilms may provide a new approach for the BSM-contaminated soil bioremediation. Root exudates and their constituent organic acids, including fumaric acid, tartaric acid, and l-malic acid, enhanced biofilm formation with 13.0-22.2% increases, owing to the regulation of genes encoding proteins responsible for cell motility/chemotaxis (fla/che cluster) and materials metabolism, thus promoting S113 population increases. Additionally, root exudates were also able to induce exopolysaccharide production to promote mature biofilm formation. Complete BSM degradation and healthy maize growth were found in BSM-contaminated rhizosphere soil treated with wild strain S113, compared to that treated with loss-of-function mutants ΔcheA-S113 (89.3%, without biofilm formation ability) and ΔsulE-S113 (22.1%, without degradation ability) or sterile water (10.7%, control). Furthermore, the biofilm mediated by organic acids, such as l-malic acid, exhibited a more favorable effect on BSM degradation and maize growth. These results showed that root exudates and their components (such as organic acids) can induce the biosynthesis of the biofilm to promote BSM degradation, emphasizing the contribution of root biofilm in reducing BSM damage to maize.

A Superefficient Ochratoxin A Hydrolase with Promising Potential for Industrial Applications.

As the most seriously controlled mycotoxin produced by Aspergillus spp. and Penicillium spp., ochratoxin A (OTA) results in various toxicological effects and widely contaminates agro-products. Biological detoxification is the highest priority regarding OTA in food and feed industry, but currently available detoxification enzymes have relatively low effectiveness in terms of time and cost. Here we show a superefficient enzyme, ADH3, identified from Stenotrophomonas acidaminiphila that has a strong ability to transform OTA into nontoxic ochratoxin-α by acting as an amidohydrolase. Recombinant ADH3 (1.2 µg/mL) completely degrades 50 µg/L OTA within 90 s, while the other most efficient OTA hydrolases available take several hours. The kinetic constant showed that rADH3 (Kcat/Km) catalytic efficiency was 56.7 to 35,000 times higher than those of previous hydrolases rAfOTase, rOTase, and commercial carboxypeptidase A (CPA). Protein structure-based assay suggested that ADH3 has a preference for hydrophobic residues to form a larger hydrophobic area than other detoxifying enzymes at the cavity of the catalytic sites, and this structure allows OTA easier access to the catalytic sites. In addition, ADH3 shows considerable temperature adaptability to exert hydrolytic function at the temperature down to 0°C or up to 70°C. Collectively, we report a superefficient OTA detoxifying enzyme with promising potential for industrial applications. IMPORTANCE Ochratoxin A (OTA) can result in various toxicological effects and widely contaminates agro-products and feedstuffs. OTA detoxifications by microbial strains and bio-enzymes are significant to food safety. Although previous studies showed OTA could be transformed through several pathways, the ochratoxin-α pathway is recognized as the most effective one. However, the most currently available enzymes are not efficient enough. Here, a superefficient hydrolase, ADH3, which can completely transform 50 µg/L OTA into ochratoxin-α within 90 s was screened and characterized. The hydrolase ADH3 shows considerable temperature adaptability (0 to 70°C) to exert the hydrolytic function. Findings of this study supplied an efficient OTA detoxifying enzyme and predicted the superefficient degradation mechanism, laying a foundation for future industrial applications.

Propranolol Suppresses Proliferation and Migration of HUVECs through Regulation of the miR-206/VEGFA Axis.

Propranolol has been used in the first-line therapy of infantile hemangioma (IH) for a number of years; however, the mechanisms through which propranolol regulates IH are not yet fully understood. In the present study, microRNA (miRNA/miR) sequencing analysis was performed to identify differentially expressed miRNAs in human umbilical vascular endothelial cells (HUVECs) treated with propranolol. Cell viability and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. Cell migration was assessed using wound healing, Transwell, and tube formation assays. Methylation-specific PCR was then used to investigate the promoter methylation status. The levels of oxidative stress indicators, including superoxide dismutase, glutathione, and malondialdehyde were also detected. Finally, cell cycle analysis was performed using flow cytometry and western blotting. It was observed that propranolol induced the upregulation of miR-206 in HUVECs, which was caused by demethylation of the miR-206 promoter. Moreover, propranolol significantly inhibited the proliferation of HUVECs by inducing apoptosis, while these phenomena were reversed by miR-206 antagomir. VEGFA was found to be a target gene of miR-206. In addition, propranolol notably inhibited the migration and induced G1 arrest of the HUVECs, whereas these results were eliminated by miR-206 antagomir. Collectively, the findings of the present study demonstrated that propranolol may inhibit the proliferation and migration in HUVECs via modulating the miR-206/VEGFA axis. These findings suggest a novel mechanism through which propranolol suppresses the progression of IH.

The low-nanomolar 4-nitrobenzoate-responsive repressor PnbX negatively regulates the actinomycete-derived 4-nitrobenzoate-degrading pnb locus.

Nitroaromatic compounds pose severe threats to public health and environmental safety. Nitro group removal via ammonia release is an important strategy for bacterial detoxification of nitroaromatic compounds, such as the conversion of 4-nitrobenzoate (4-NBA) to protocatechuate by the bacterial pnb operon. In contrast to the LysR-family transcriptional regulator PnbR in proteobacteria, the actinomycete-derived pnb locus (4-NBA degradation structural genes) formed an operon with the TetR-family transcriptional regulator gene pnbX, implying that it has a distinct regulatory mechanism. Here, pnbBA from the actinomycete Nocardioides sp. strain LMS-CY was biochemically confirmed to express 4-NBA degradation enzymes, and pnbX was essential for inducible degradation of 4-NBA. Purified PnbX-6His could bind the promoter probe of the pnb locus in vitro, and 4-NBA prevented this binding. 4-NBA could bind PnbX at a 1:1 molar ratio with KD  = 26.7 ± 4.2 nM. Low-nanomolar levels of 4-NBA induced the transcription of the pnb operon in strain LMS-CY. PnbX bound a palindromic sequence motif (5'-TTACGTTACA-N8 -TGTAACGTAA-3') that encompasses the pnb promoter. This study identified a TetR-family repressor for the actinomycete-derived pnb operon that recognizes 10-8  M 4-NBA as its ligand, implying that nitro group removal of nitroaromatic compounds may be especially important for actinomycetes.

The complete chloroplast genome of Mucuna sempervirens (Fabaceae: Papilionoideae).

The complete chloroplast genome of Mucuna sempervirens reported herein was a circular DNA molecule of 154,542 bp in length. The genome had a typical quadripartite structure, consisting of a pair of inverted repeats (IRa and IRb: 24,836 bp) separated by a large single-copy region (LSC: 67,996 bp) and a small single-copy region (SSC: 18,363 bp). The overall GC content of the genome was 35.1%. The cp genome encoded a set of 128 genes, containing 82 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that M. sempervirens was sister to M. macrocarpa. These findings may provide useful information to the phylogeny of the genus Mucuna.

miR-30a-5p targets Becn1 to ameliorate high-glucose-induced glomerular podocyte injury in immortalized rat podocyte cell line.

OBJECTIVE: Diabetic nephropathy (DN) is a serious kidney-based complication of diabetes, wherein podocyte injury is deemed crucial in the development of early stage. Various miRNAs, as report goes, is involved in the pathogenesis of varieties of kidney diseases including DN. In this study, we found a target relationship between miR-30a-5p and Becn1, of which there are few studies about the role in podocyte injury. We therefore used immortalized rat podocyte cell line to explore the role and molecular mechanism of miR-30a-5p targeting Becn1 gene in high-glucose-induced glomerular podocyte injury. METHODS: The mRNA and protein expressions of miR-30a-5p and Becn1 were detected respectively by quantitative reverse transcriptase PCR and western blotting. The proliferation, apoptosis, and the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected by MTT assay, flow cytometry, and enzyme-linked immuno sorbent assay, respectively. Intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also determined. RESULTS: Compared with normal group, miR-30a-5p in model groups were down-regulated, while Becn1 expression was significantly up-regulated, with slower proliferation, higher apoptosis rate, lower SOD level, and significantly higher ROS, MDA, IL-6, and TNF-α levels (all P<0.05). Overexpression of miR-30a-5p or Becn1 knock-out could lower Becn1 expression, apoptosis rate, promote proliferation, with relatively higher SOD level and lower ROS, MDA, Il-6, and TNF-α levels of model cells (all P<0.05). CONCLUSION: Up-regulation of miR-30a-5p can suppress the expression of Becn1 to increase the growth and inhibit the apoptosis of immortalized rat podocyte cell line, therefore ameliorating podocyte injury induced by high glucose in vitro.

Comments on the ochratoxin A degradation mechanism by Lysobacter sp. CW239 - Wei Wei et al. (2020).

This is a research comment on the ochratoxin A (OTA) degradation mechanism by Lysobacter sp. CW239 regarding the previous publication in Environmental Pollution (Wei et al., 2020). Three possible degradation mechanisms were discussed in the referred publication, but without definite evidences, it was not clear which one worked actually. Here, the gene cp4 deficient mutant CW239Δcp4 was successfully constructed, and the carboxypeptidase CP4 role on OTA degradation in strain CW239 was validated in vivo. As a result, the mutant CW239Δcp4 without gene cp4 showed less than 10% reduction of 24 hrs degradation ratio compared to wide-type strain CW239. After the gene cp4 complemented to CW239Δcp4, the complementary strain (+)cp4 recovered the degradation ability to wide-type. The validation result indicated that the third degradation mechanism (i.e., OTA is degraded by joint action of multiple enzymes in CW239) proposed previous (Wei et al., 2020) was correct route for the degradation strain. This commentary was significant to the following studies on the pollutant detoxify strains with similar degradation characters between identified enzyme and the host strain.

Multicenter Investigation of the Initial Hemodialysis Vascular Access and Its Related Factors in Hangzhou of China.

OBJECTIVE: To investigate the initial hemodialysis vascular access in Hangzhou and provide evidence for improving the use of autologous arteriovenous fistula by identifying factors associated with the choice of initial vascular access. METHODS: We retrospectively studied the initial hemodialysis vascular access of 257 patients in five hemodialysis units in Hangzhou of China during a 21-month period (January 2018 to September 2019). A logistic regression was used to identify the risk factors of failing to use an arteriovenous fistula at the initiation of hemodialysis. RESULTS: (1) 257 participants with mean age 67.65 ± 13.43 years old were reviewed, including 165 males (64.2%) and 92 females (35.8%). The etiologies of end-stage renal disease included diabetic nephropathy (37.35%), chronic glomerulonephritis (31.13%), hypertensive nephropathy (14.01%), and other diseases (17.51%). Only 51 patients (19.84%) received arteriovenous fistula, whereas the remaining 206 patients (80.16%) initiated dialysis with a central venous catheter. (2) Logistic regression analysis revealed that the independent risk factors for central venous catheter at the initial hemodialysis were age >70 years old (OR = 4.827, p < 0.01 versus ≤70 years old), chronic glomerulonephritis as the primary etiology (OR = 2.565, p < 0.05 versus nonchronic glomerulonephritis) and eGFR <8.5 mL/min/1.73m2 (OR = 2.283, p < 0.05 versus eGFR ≥8.5 mL/min/1.73m2). CONCLUSION: The proportion of patients using arteriovenous fistula as the initial hemodialysis vascular access in Hangzhou was still low. The choice of vascular access for the first hemodialysis was related to age, eGFR, and the primary etiology of end-stage renal disease. Increasing the proportion of planned vascular access and arteriovenous fistula at the initiation of hemodialysis is still our current goal.

P2X7 receptor signaling promotes inflammation in renal parenchymal cells suffering from ischemia-reperfusion injury.

Extracellular adenosine triphosphate (ATP) and its receptor, P2X7 receptor (P2X7R), are playing an important role in the pathological process of renal ischemia-reperfusion injury, but their underlying mechanism remains unclear. Also, the effects of tubular epithelium-expressed P2X7 receptor on ischemia acute kidney injury is still unknown. The aim of this study is to clarify if this mechanism involves the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the renal tubular epithelial cells. In our research, we used male C57BL/6 wild type and P2X7R (-/-) mice, cultured human proximal tubular epithelial cells, and kidneys from acute kidney injury patients. Mice underwent for unilateral nephrectomy combined with the lateral renal pedicle clamping. Cultured cells were subjected to hypoxia/reoxygenation or ATP. Apyrase and A438079 were used to block the extracellular ATP/P2X7 receptor pathway. We also constructed radiation-induced bone marrow (BM) chimeras by using P2X7R (-/-) mice and P2X7R (+/+) wild-type mice. P2X7 receptor deficiency protected from renal ischemia-reperfusion injury and attenuated the formation of NLRP3 inflammasome. By using BM chimeras, we found a partial reduction of serum creatinine and less histological impairment in group wild-type BM to P2X7R (-/-) recipient, compared with group wild-type BM to wild-type recipient. In renal tubular epithelial cells, hypoxia/reoxygenation induced ATP release and extracellular ATP depletion reduced the expression of active IL-1ß. ATP activated the NLRP3 inflammasome in renal tubular epithelial cells, which were blunted by transient silence of P2X7 receptor, as well as by P2X7 receptor blocking with A438079. In human samples, we found that patients with Stage 3 AKI had higher levels of P2X7 receptor expression than patients with Stage 1 or Stage 2. Extracellular ATP/P2X7 receptor axis blocking may protect renal tubular epithelial cells from ischemia-reperfusion injury through the regulation of NLRP3 inflammasome.

Prognostic value of pretreatment platelet counts in lung cancer: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its precise role in these patients. METHODS: We employed a multiple search strategy in the PubMed, EMBASE and Cochrane Library databases to identify eligible studies. Disease-free survival (DFS)/progression-free survival (PFS)/time to progression (TTP) and overall survival (OS) were used as outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity among the studies and publication bias were also evaluated. RESULTS: A total of 40 studies including 16,696 lung cancer patients were eligible for the analysis. Overall, the pooled analysis showed that compared with normal platelet counts, elevated pretreatment platelet counts were associated with poorer OS (HR = 1.54, 95% CI: 1.37-1.72, P < 0.001) and poorer DFS/PFS/TTP (HR = 1.62, 95% CI: 1.33-1.98, P < 0.001) in patients with lung cancer. In subgroup analyses, elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups. There was no evidence of publication bias. CONCLUSIONS: This meta-analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients. Large-scale prospective studies and a validation study are warranted.

Detoxification of aflatoxin B1 by Stenotrophomonas sp. CW117 and characterization the thermophilic degradation process.

Mycotoxins are high toxic, widely distributed contaminants in foodstuff. In this study, a aflatoxin B1 (AFB1) degrading strain S. acidoaminiphila CW117 was screened, and its detoxification characteristics were investigated. Substrate AFB1 at 45 µg/L was degraded by CW117 within 24 h; meanwhile, 4.1 mg/L AFB1 was almost degraded within 48 h. After 24 h degradation, the biotoxicity of the detoxified culture was eliminated. Strain CW117 efficient degradation to AFB1 (especially to low AFB1 concentrations) suggested its potential significance to detoxification development on food and feedstuff. The active degradation components present in the cell-free supernatant. The degradation ratio increased constantly with increasing incubation temperature raised (0-90 °C) and was even stable at 90 °C. Degradation was optimal at pH 6-7, and was only partially inhibited by metal-chelators (EDTA and EGTA), proteinase K, and a protein denaturant (sodium dodecyl sulfate, SDS). The recombinant laccase rLC1 (0.5 mg/mL) from CW117 degraded 29.3% of AFB1 within 24 h; however, the cell-free supernatant degraded 76.7% of the toxin in same time, with much lower protein content. The results indicated the CW117 degrades AFB1 via a combination of enzymes and micro-molecule oxides.

The Role of the AIMP1 Pathway in Diabetic Retinopathy: AIMP1-Targeted Intervention Study in Diabetic Retinopathy.

INTRODUCTION: We characterized the role of aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) in retinal inflammation and apoptosis regulation, both in vivo and in vitro. In addition, we used clinical specimens to show the relationship between AIMP1 and the development of diabetic retinopathy (DR). OBJECTIVE: To elucidate the role of AIMP1 in DR. METHODS: A diabetic AIMP1-specific knockout (KO) C57 mouse model was used. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal glucose, high glucose (HG), and HG + AIMP1-small interfering RNA (siRNA). The expression of AIMP1 and relative inflammatory and apoptotic cytokines in diabetic mice retina and HRMECs were measured using Western blotting and polymerase chain reaction. The apoptosis of HRMECs was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The levels of AIMP1 in the vitreous humor and serum were determined using ELISA. Possible correlations between the intravitreal level of AIMP1 and blood glucose, glycosylated hemoglobin HbA1c, intravitreal levels of IL-1ß, and caspase-3 were determined. RESULTS: The expression of inflammatory and apoptotic proteins was inhibited in the AIMP1 KO mice and HRMECs incubated with AIMP1-siRNA. The apoptosis of HRMECs was decreased in the AIMP1-siRNA group. The intravitreal level of AIMP1 in DR patients was significantly higher than that in nondiabetic patients (p < 0.01). There was a positive correlation between intravitreal AIMP1 and HbA1c and intravitreal IL-1ß and caspase-3 (p < 0.05). CONCLUSIONS: HG induced increased expression of AIMP1 in HRMECs and retinas from diabetic C57 mice, thereby increasing the expression of inflammatory and apoptotic cytokines, which promoted DR progression. A decrease in AIMP1 expression prevented the development of DR by inhibiting the activation of inflammatory and apoptotic signaling. Therefore, AIMP1 is an effective interfering target for the prevention and treatment of DR.

Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease.

AIM: Muscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post-translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle. METHODS: Twenty patients with stage 4-5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other eight non-CKD surgical subjects' muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real-time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology. RESULTS: CKD patients had lower HGS than non-CKD subjects, and HGS was correlated with gender, age, haemoglobin and albumin. Mitochondria were decreased in end-stage renal disease (ESRD) patients muscle. Mfn-1 expression and phospho-Drp1(S637)/Drp1 ratio were inhibited in the ESRD group, implicating dysfunctional mitochondrial dynamics. Muscle PDH activity and phospho-PDH(S293) were decreased in ESRD patient muscle, while PDK4 protein level was up regulated. CONCLUSION: Decreased mitochondria and PDH deficiency caused by up regulation of PDK 4 contribute to muscle dysfunction, and could be responsible for muscle weakness in CKD patients.