Design and analysis of self-priming extension DNA hairpin probe for miRNA detection based on a unified dynamic programming framework.

MicroRNAs (miRNAs) are potential biomarkers for cancer diagnosis and prognosis, methods for detecting miRNAs with high sensitivity, selectivity, and stability are urgently needed. Various nucleic acid probes that have traditionally been for this purpose suffer several drawbacks, including inefficient signal-to-noise ratios and intensities, high cost, and time-consuming method establishment. Computing tools used for investigating the thermodynamics of DNA hybridization reactions can accurately predict the secondary structure of DNA and the interactions between DNA molecules. Herein, NUPACK was used to design a series of nucleic acid probes and develop a phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP) signal amplification strategy, which enabled the ultrasensitive detection of miR-200a in serum samples. The free and binding energies of the DNA detection probes calculated using NUPACK, as well as the biological experimental results, were considered synthetically to select the best sequence and experimental conditions. A unified dynamic programming framework, NUPACK analysis and the experimental data, were complementary and improved the designed model in all respects. Our study demonstrates the feasibility of using computer technology such as NUPACK to simplify the experimental process and provide intuitive results.

[Differentially expressed microRNAs in peripheral blood mononuclear cells of ankylosing spondylitis patients and its correlation with immune inflammatory response].

Objective To investigate the differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients, and explore its relevance with the immune inflammatory responses. Methods Fifteen AS patients (AS group) and fifteen healthy volunteers (control group) were recruited in this research. High-throughput RNA sequencing was used to screen miRNA expression in PBMCs. Real-time quantitative PCR was used to detect the six differentially expressed miRNAs. ELISA was applied to test the levels of proinflammatory cytokines, such as TNF-α, IL-1ß, IL-17, and IL-23. Finally, Spearman correlation analysis was conducted to study the correlations of differentially expressed miRNAs with disease activity indicators and immune inflammatory markers. Results Forty-four miRNAs were significantly differentially expressed in AS patients, manifested as 22 up-regulated and 22 down-regulated (fold change≥1). Among them, miR-1-3p and miR-133a-5p were up-regulated obviously, while miR-127-5p, miR-345-3p and miR-136-3p were down-regulated significantly. TNF-α, IL-1ß, IL-17 and IL-23 were significantly increased simultaneously in AS patients. Moreover, miR-1-3p was positively correlated with TNF-α, CRP and BASDAI score; miR-133a-5p was positively correlated with TNF-α; miR-127-5p was negatively correlated with ESR and VAS; miR-345-3p was negatively correlated with IL-17; miR-136-3p was negatively correlated with IL-17 and BASDAI score. Conclusion The miRNAs are abnormally expressed in PBMCs of AS patients, and the differentially expressed miRNAs are associated with disease activity indicators and immune inflammatory cytokines.

Constructing green superhydrophilic and superoleophobic COFs-MOFs hybrid-based membrane for efficiently emulsion separation and synchronous removal of microplastics, dyes, and pesticides.

Oil spills and micropollutants have become thorny environmental issues, posing serious threat to ecosystem and human health. To settle such dilemma, this study successfully constructed a robust and environmentally-friendly MOFs-COFs hybrid-based membrane (FS-50/COF(MATPA)-MOF(Zr)/PDA@PVDF) for the first time through solution synthesis and solvothermal method, combined with surface modification of FS-50 molecule. Importantly, we employed a simple two-step strategy to obtain the high-aspect-ratio MOFs fibers: (1) solvent regulation to generate smaller needle-like whiskers during the in-situ growth of MOFs on COFs; (2) high pressure induced directional crystallization in filtration process. The introduction of polydopamine (PDA) greatly improved the adhesion between coating and PVDF membrane. The in-situ growth of high length-diameter ratio MOFs fibers on blocky COFs greatly enhanced the specific surface area of MOFs-COFs hybrid, thus provided sufficient absorption sites. The functional groups of FS-50 endowed the hybrid membrane with superhydrophilicity and superoleophobicity, which facilitated to selectively penetrate water molecules and repel non-polar pollutants. The separation efficiency and decontamination mechanism of hybrid membrane to the simulated oily wastewater (containing various MPs, dyes, and pesticides) were investigated through experiments and theoretical calculations. The hybrid membrane could selectively and synchronously adsorb various dyes (20 mg/L-120 mg/L, almost 100% removal) and pesticides (10 mg/L for DIF and TET, adsorption rates 93.2% and 90.9%, respectively) from oil-water emulsion (50 mL). The large-scale coated sponge (6 cm × 4.5 cm × 3 cm) could quickly achieve separation of oil-water mixture (almost 100%) with a water permeability of more than 162 L m-2·h-1·bar-1, and simultaneously remove various MPs (PP-2000, PP-100, PE-2000, PS-100, 0.2 g/300 mL for each), Sudan Ⅲ (C0 = 200 mg/L), and DIF (C0 = 10 mg/L) from a simulant oily wastewater (300 mL), with the removal rates of almost 100% for MPs, 99.7% for Sudan Ⅲ, and 95.8% for DIF. Furthermore, we elucidated the removal mechanism of pesticide and dyes through simulating the theoretical adsorption energy and potential adsorption sites. The hybrid membrane not only provides a promising candidate for the removal of multiple pollutants from oil-water emulsion, but also opens a new strategy for achieving efficient and clean aquatic environment restoration.

Xinfeng capsule inhibits lncRNA NONHSAT227927.1/TRAF2 to alleviate NF-κB-p65-induced immuno-inflammation in ankylosing spondylitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ankylosing spondylitis (AS) is a chronic rheumatic disease known for its insidious and refractory symptoms, primarily associated with immuno-inflammation in its early stages, that affects the self-perception of patients (SPP). The exploration of long noncoding RNA (lncRNA) in immuno-inflammation of AS has garnered considerable interest. Additionally, the effectiveness of traditional Chinese medicine Xinfeng Capsule (XFC) in mitigating immuno-inflammation in AS has also been observed. However, the specific mechanisms still need to be characterized. AIM OF THE STUDY: This study elucidated the mechanism of the lncRNA NONHSAT227927.1/TRAF2/NF-κB axis in the immuno-inflammation of AS and XFC in AS treatment. METHODS: LncRNA NONHSAT227927.1 and mRNA expression were assessed utilizing real-time fluorescence quantitative PCR. Protein level was determined using Western blot, and cytokine expression was measured using ELISA. Furthermore, mass spectrometry was used to analyze the binding proteins of lncRNA and rescue experiments were conducted to validate the findings. Inconsistencies in clinical baseline data were addressed using propensity score matching. The association between the XFC effect and indicator changes was evaluated using the Apriori algorithm. RESULTS: The study revealed a substantial elevation in the expression of lncRNA NONHSAT227927.1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) in AS-peripheral blood mononuclear cells. Its expression was also notably reduced after XFC treatment. In addition to this, there was a positive correlation between lncRNA NONHSAT227927.1 and TRAF2 with clinical immuno-inflammatory indicators. On the other hand, they showed a negative association with the SPP indicators. In vitro experiments have demonstrated that lncRNA NONHSAT227927.1 activated the nuclear factor (NF)-κB-p65 pathway by promoting TRAF2 expression. This activation resulted in enhanced IL-6 and TNF-α levels and reduced IL-10 and IL-4 levels. Conversely, XFC decreased the expression of lncRNA NONHSAT227927.1 and TRAF2, inhibiting the stimulation of the NF-κB-p65 cascade and restoring balance to the cytokines. The association rule analysis results indicated a strong association between XFC and decreased levels of C-reactive protein, erythrocyte sedimentation rate, and immunoglobulin A. Furthermore, XFC was strongly associated with improved SPP indicators, including general health, vitality, mental health, and role-emotional. CONCLUSIONS: LncRNA NONHSAT227927.1 plays a pro-inflammatory role in AS. XFC treatment may reverse lncRNA NONHSAT227927.1 to suppress TRAF2-mediated NF-κB-p65 activation, which in turn suppresses immuno-inflammation and improves SPP, thereby making XFC a promising candidate for therapeutic applications in AS management.

Traditional Chinese medicine may be associated with a reduced risk of recurrent exacerbation in patients with rheumatoid arthritis: A matched cohort study based on 1383 individuals.

Ethnopharmacological relevance: This study determines whether traditional Chinese medicine (TCM) treatment is associated with the risk of recurrent exacerbation in patients with rheumatoid arthritis (RA). Materials and methods: In this retrospective study, we selected 1383 patients who were diagnosed with RA between 2013 and 2021 from the medical record information management system of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Then, patients were classified into TCM users and non-TCM users. Gender, age, recurrent exacerbation, TCM, death, surgery, organ lesions, Chinese patent medicine, external medicine, and non-steroidal anti-inflammatory drugs were adjusted one TCM user-to-one non-TCM user with propensity score matching to reduce selection bias and confusion using propensity score matching (PSM). A Cox regression model was used to compare the hazard ratio of the risk of recurrent exacerbation and the Kaplan Meier curve of recurrent exacerbation proportion between the two groups. Results: Most of the tested clinical indicators in this study improved in patients, which was correlated with the use of TCM, with a statistical significance. TCM was preferred in female and younger (<58 years old) patients with RA. Of note, recurrent exacerbation was observed in more than 850 (61.461%) RA patients. The results of the Cox proportional hazard model showed TCM as a protective factor for the recurrent exacerbation of RA patients (HR = 50%, 95% CI = 0.65-0.92, P < 0.01). Kaplan Meier curves demonstrated that the survival rate of TCM users was higher than that of non-TCM users (log-rank P < 0.01). Conclusion: Conclusively, the use of TCM may be related to a lower risk of recurrent exacerbation in RA patients. These findings provide evidence for the recommendation of TCM treatment for RA patients.

Exposure to dithiocarbamate fungicide maneb in vitro and in vivo: Neuronal apoptosis and underlying mechanisms.

Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson's disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo. In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.

Exposure to the environmentally toxic pesticide maneb induces Parkinson's disease-like neurotoxicity in mice: A combined proteomic and metabolomic analysis.

Maneb is a typical dithiocarbamate fungicide that has been extensively used worldwide. Epidemiological evidence shows that exposure to maneb is an environmental risk factor for Parkinson's disease (PD). However, the mechanisms underlying maneb-induced neurotoxicity have yet to be elucidated. In this study, we exposed SH-SY5Y cells to maneb at environmentally relevant concentrations (0, 0.1, 5, 10 mg/L) and found that maneb dose-dependently decreased the cell viability. Furthermore, maneb (60 mg/kg) induced PD-like motor impairment in α-synuclein A53T transgenic mice. The results of tandem mass tag (TMT) proteomics and metabolomics studies of mouse brain and serum revealed significant changes in proteins and metabolites in the pathways involved in the neurotransmitter system. The omics results were verified by targeted metabolomics and Western blot analysis, which demonstrated that maneb induced disturbance of the PD-related pathways, including the phenylalanine and tryptophan metabolism pathways, dopaminergic synapse, synaptic vesicle cycle, mitochondrial dysfunction, and oxidative stress. In addition, the PD-like phenotype induced by maneb was attenuated by the asparagine endopeptidase (AEP) inhibitor compound #11 (CP11) (10 mg/kg), indicating that AEP may play a role in maneb-induced neurotoxicity. To the best of our knowledge, this is the first study to investigate the molecular mechanisms underlying maneb-induced PD-like phenotypes using multiomics analysis, which identified novel therapeutic targets for PD associated with pesticides and other environmental pollutants.

Radix Salvia miltiorrhiza for Ankylosing Spondylitis: Determining Potential Inflammatory Molecular Targets and Mechanism Using Network Pharmacology.

Radix Salvia miltiorrhiza (RSM) is widely used for the clinical improvement of inflammatory diseases. However, the actions of RSM in the treatment of ankylosing spondylitis (AS) have not been fully explored. Therefore, this study was designed to use retrospective clinical data mining approach to understand the effects of RSM on AS-related immuno-inflammatory processes, use network pharmacology to predict therapeutic targets of RSM, and to further investigate the pharmacological molecular mechanism in vitro. RSM treatment has a long-term correlation with the improvement of AS-related immuno-inflammatory indicators through computational models. We established protein-protein interaction networks, conducted KEGG analysis to enrich significant TNF pathways, and finally obtained three core targets of RSM in the treatment of AS, namely, prostaglandin endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Screening of RSM active ingredients with node degree greater than 20 yielded cryptotanshinone and tanshinone IIA, and previous studies have reported their anti-inflammatory effects. In vitro, both cryptotanshinone and tanshinone IIA significantly inhibited the expressions of PTGS2, IL-6, and TNF-α in peripheral blood mononuclear cells in AS patients. In conclusion, cryptotanshinone and tanshinone IIA, which are the active components of RSM, may inhibit the activation of TNF signaling pathway in AS patients by downregulating the expression of PTGS2, IL-6, and TNF-α. These findings illustrate that RSM may be a promising therapeutic candidate for AS, but further validation is required.

Knockdown of circular RNA hsa_circ_0003307 inhibits synovial inflammation in ankylosing spondylitis by regulating the PI3K/AKT pathway.

BACKGROUND: Ankylosing spondylitis (AS) has a high disability rate, and an early diagnosis is difficult. OBJECTIVES: To explore the possible functions and underlying mechanism of circular RNAs Homo sapiens (hsa)_circ_0003307 in ankylosing spondylitis. MATERIAL AND METHODS: The hsa_circ_0003307 expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of 30 AS patients and 30 healthy controls (HC) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues, established as cell lines and cultured for subsequent cell experiments involving transfection with different vectors. The qRT-PCR analysis was used for evaluating the levels of hsa_circ_0003307 in AS-FLS. Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein levels were measured using western blotting and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. Spearman's correlation analysis was used to assess the correlation between hsa_circ_0003307 and clinical characteristics. RESULTS: The expression level of hsa_circ_0003307 was significantly high in AS patients and was positively associated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). We found that hsa_circ_0003307 overexpression could promote the activation of the PI3K/AKT pathway and expression of inflammatory cytokines - tumor necrosis factor alpha (TNF-α) and TNF-α-induced protein 2 (TNFAIP2). However, hsa_circ_0003307 knockdown reduced the expression of TNF-α and TNFAIP2. CONCLUSIONS: The expression level of hsa_circ_0003307 was associated with inflammatory response, and it was revealed that hsa_circ_0003307 knockdown could reduce the inflammatory response of AS by regulating the PI3K/AKT pathway.

Trace Metal Lead Exposure in Typical Lip Cosmetics From Electronic Commercial Platform: Investigation, Health Risk Assessment and Blood Lead Level Analysis.

Lead (Pb) in lipstick products has become an increasing concern, which can cause safety problems to human body directly with diet. To investigate the Pb exposure and potential health risk level of typical popular lip cosmetics in Chinese e-commerce market, Python crawler was introduced to identify and select 34 typical popular lip cosmetics, including 12 lipsticks, 13 lip glosses, and 9 lip balms. And then this study used ICP-MS to determine the content of Pb. Furthermore, the ingestion health risk assessment method issued by United States Environmental Protection Agency (USEPA) and Monte Carlo simulation algorithm were applied to assess the probabilistic health risks of adults exposure. Finally, taking the possible exposure of children contacting with lip products, the health risk assessment of children blood Pb was carried out. The results showed that the concentration of Pb in lip products ranged from 0 to 0.5237 mg/kg, which was far lower than the limit set by various countries. The probabilistic non-carcinogenic risks and carcinogenic risks were 4.93 ×10-7~2.82 ×10-3 and 1.68 ×10-12~9.59 ×10-9, respectively, which were in an acceptable level. The results of blood Pb assessment suggested that the Pb content of lip cosmetics had no obvious influence on blood Pb concentration of children, and background Pb exposure is the main factor affecting children's blood Pb level (BLL). Overall, the samples of lip products are selected by Python crawler in this study, which are more objective and representative. This study focuses on deeper study of Pb, especially for the health risk assessment of blood Pb in children exposed to lip products. These results perhaps could provide useful information for the safety cosmetics usage for people in China and even the global world.

Selective photodynamic inactivation of Helicobacter pylori by a cationic benzylidene cyclopentanone photosensitizer - an in vitro and ex vivo study.

The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm2 532 nm laser, Y1, P1 and P3 at 2.5 µM induced a 3-log10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 µM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 µM led to a complete eradication of H. pylori under the irradiation of 24 J/cm2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues.

Prognostic nomograms and risk-stratifying systems for predicting survival in patients with resected pT2-4aN0M0 esophageal carcinoma.

BACKGROUND: According to the National Comprehensive Cancer Network (NCCN) guidelines, surveillance or adjuvant chemoradiation is recommended for patients with completely resected pT2-4aN0M0 esophageal carcinoma (EC). Due to this population's variant prognosis, we developed novel nomograms to define the high-risk patients who may need closer follow-up or even post-operative therapy. METHODS: Cases with resected pT2-4aN0M0 EC from the Surveillance, Epidemiology, and End Results (SEER) database and the Sun Yat-sen University Cancer Center (SYSUCC) were enrolled in the study. The SEER database cases were randomly assigned into the training cohort (SEER-T) and the internal validation cohort (SEER-V). Cases from the SYSUCC served as the external validation cohort (SYSUCC-V). Overall survival (OS) and cancer specific survival (CSS) were compared between groups. Multivariate analyses were applied to identify the prognostic factors. Nomograms and risk-classifying systems were developed. The nomograms' performances were evaluated by concordance index (C-index), calibration plots and decision curve analysis (DCA). RESULTS: A total of 2,441 eligible EC cases (SEER-T, n=839; SEER-V, n=279; SYSUCC-V, n=1,323) were included. Age, sex, chemotherapy, lymph node harvested (LNH) and T stage were identified as the independent predictors for CSS. Regarding OS, it also included the prognostic factor of histology. Nomograms were formulated. For CSS, the C-index was 0.68 [95% confidence interval (CI): 0.66-0.71], 0.67 (95% CI: 0.63-0.71) and 0.61 (95% CI: 0.59-0.63) for the SEER-T, SEER-V, and SYSUCC-V, respectively. For OS, the C-index was 0.69 (95% CI: 0.66-0.72), 0.64 (95% CI: 0.59-0.69) and 0.62 (95% CI: 0.61-0.63) for the SEER-T, SEER-V, and SYSUCC-V, respectively. The calibration curves and DCA showed good performances of the nomograms. In further analyses, risk-classification systems stratified pT2-4aN0M0 EC into low-risk and high-risk subgroup. The OS and CSS curves of these 2 subgroups, in the full analysis set or stratified by TNM stage, histology, T stage and LNH categories, showed significant distinctions. CONCLUSIONS: The novel prognostic nomograms and risk-stratifying systems which separated resected pT2-4aN0M0 esophageal carcinoma patients into the low-risk and high-risk prognostic groups were developed. It may help clinicians estimate individual survival and develop individualized treatment strategies.

Resistin-like molecule ß acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK signaling pathways.

BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule ß (RELM-ß) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-ß has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-ß in HPH remain unclear. METHODS: We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-ß in a rat HPH model and in hPASMCs. RESULTS: Overexpression of RELM-ß caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-ß partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-ß gene overexpression or silencing, respectively. Recombinant RELM-ß protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-ß on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. CONCLUSIONS: Our findings suggest that RELM-ß acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-ß are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.

The effectiveness of nanobiochar for reducing phytotoxicity and improving soil remediation in cadmium-contaminated soil.

There is growing concern that Cd in soils can be transferred to plants, resulting in phytotoxicity and threats to human health via the food chain. Biochar has been reported to be a soil amendment capable of reducing the bioavailability of metals in soil by electrostatic interactions, ionic exchange and the specific binding of metal ions by surface ligands. To determine the effects of Cd contamination and nanobiochar on the growth characteristics of plants, the dynamics of Cd in soil were explored in Petri dish and pot experiments (0%, 0.2%, 0.5% and 1% nanobiochar), respectively. The diversity, distribution and composition of the bacterial community in treated soil were monitored by high-throughput sequencing. The results showed that the germination potential and height and weight of plants were significantly decreased in Cd-treated soil samples (P < 0.05). The Cd content of Brassica chinensis L. in the treated soil groups was lower than that in the untreated soil groups (P < 0.05) after nanobiochar application. The application of biochar significantly improved the microbial biomass, microorganism abundance and diversity of Actinobacteria and Bacteroidetes in Cd-contaminated soil and reduced the diversity of Proteobacteria, which was relatively more persistent than in the contaminated sites without biochar application. The results of this study provide theoretical and technical support for understanding the environmental behavior of nanopassivators, thus enhancing the role of biochar in the remediation of soil pollution.

[Effect of triptolide in improving platelet activation in patients with ankylosing spondylitis by regulating VEGFA,SDF-1,CXCR4 pathway].

The effect of triptolide( TP) on VEGFA,SDF-1,CXCR4 pathway were investigated in vitro to explore the mechanism in improving platelet activation in patients with ankylosing spondylitis( AS). Peripheral blood mononuclear cells( PBMC) were used for the experiment and divided into 4 groups: normal group( NC),model group( MC),triptolide group( TP),and AMD3100 group. The optimal concentration of TP was measured by the MTT method. The expressions of TNF-α,IL-1ß,IL-4,IL-10,VEGFA and VEGFR were detected by ELISA. The expressions of SDF-1,CXCR4 and VEGFA were detected by real-time quantitative PCR( RT-qPCR).The expressions of SDF-1,CXCR4,VEGFA and VEGFR were detected by Western blot. The expression levels of CD62 p,CD40 L and PDGFA were detected by immunofluorescence. MTT results showed that medium-dose TP had the strongest inhibitory effect on cells at24 h. The results of ELISA and PCR showed that TP inhibited mRNA expressions of IL-1ß,TNF-α,VEGFA,VEGFR and SDF-1,CXCR4 and VEGFA. The results of Western blot indicated that TP inhibited SDF-1,CXCR4 and VEGFA,VEGFR protein expressions; immunofluorescence results indicate that TP can inhibit the expressions of CD62 p,CD40 L,PDGFA. TP may regulate platelet activation by down-regulating SDF-1,CXCR4,VEGFA and VEGFR mRNA expressions,thereby down-regulating IL-1ß and TNF-αexpressions,and up-regulating the expressions of IL-4 and IL-10 cytokines.

Polychlorinated naphthalene emissions to the atmosphere from typical secondary aluminum smelting plants in southwestern China: concentrations, characterization, and risk evaluation.

Secondary aluminum smelting industry, as an important source of polychlorinated naphthalene (PCN) in environment, has been concerned in recent years. To figure out the emission characteristics of PCNs and the potential influence on surrounding environment, two typical secondary aluminum smelting plants were selected and PCNs were determined in flue gas, fly ash, aluminum slag, soil, and air samples collected at and around the plants by GC-MS coupled with DFS. PCN emission factors from the flue gas of the two plants (mean 0.006 ng toxic equivalents/t) were found obviously decreased compared with similar smelting process detected in 2010. The stage of feeding material was still the major PCNs discharge period during the whole smelting process. The total PCN concentrations in air were found to be ranked as following: workshops (290-1917 pg/m3), the area near the workshops (62.3-697 pg/m3), and the surrounding areas (29.9-164 pg/m3, mean 64.5 pg/m3). Similar high concentrations of PCNs were found in soil from by the workshop door (983 ng/g dry weight). Soil-air exchange calculations indicated that mono-CN to tetra-CN would volatilize but hepta-CN and octa-CN would be deposited to the soil. Exposure of plant workers and local inhabitants to PCNs through inhalation was found to be acceptable but higher (especially for workers in the workshops) than living areas. The workshop and the nearby area are potential PCNs polluted areas and should be paid attention during the practical operation.

Concentrations and occupational exposure assessment of polybrominated diphenyl ethers in modern Chinese e-waste dismantling workshops.

In this work, the concentrations of polybrominated diphenyl ethers (PBDEs) were determined in air, dust and fly ash samples from three legal waste electrical and electronic equipment dismantling plants with strict pollution controls. The risks posed by PBDEs to workers at the plants were assessed. The atmospheric concentrations of PBDEs in the different e-waste recycling workshops were 0.58-2.89 × 103 ng/m3, and predominantly distributed in the particle phase (90.7%-99.9%). The concentrations of the PBDEs in the floor dust and fly ash samples from bag-type dust collectors in different workshops were 2.39-125 µg/g, 5.84-128 µg/g, respectively. The contributions of BDE-209 in air, floor dust and fly ash samples were 84.0%-97.9%, 11.2%-95.3% and 74.0%-94.9%, respectively, indicating that deca-BDE commercial formulations were their major sources. Daily exposure to PBDEs was also lower than has been found for workers in other recycling workshops. Human exposures to BDE-47, BDE-99, BDE-153, and BDE-209 were all below the levels considered to pose appreciable risks. Dust ingestion was the main exposure route for manual recyclers, and inhalation was the main exposure route for waste transportation workers. The results of this study indicate that PBDEs emissions and risks are lower in modern, legal e-waste recycling facilities with effective pollution controls. However, the effectiveness of the pollution controls need to be further researched in plastic crushing areas.

Immobilization of Photo-Immunoconjugates on Nanoparticles Leads to Enhanced Light-Activated Biological Effects.

The past three decades have witnessed notable advances in establishing photosensitizer-antibody photo-immunoconjugates for photo-immunotherapy and imaging of tumors. Photo-immunotherapy minimizes damage to surrounding healthy tissue when using a cancer-selective photo-immunoconjugate, but requires a threshold intracellular photosensitizer concentration to be effective. Delivery of immunoconjugates to the target cells is often hindered by I) the low photosensitizer-to-antibody ratio of photo-immunoconjugates and II) the limited amount of target molecule presented on the cell surface. Here, a nanoengineering approach is introduced to overcome these obstacles and improve the effectiveness of photo-immunotherapy and imaging. Click chemistry coupling of benzoporphyrin derivative (BPD)-Cetuximab photo-immunoconjugates onto FKR560 dye-containing poly(lactic-co-glycolic acid) nanoparticles markedly enhances intracellular photo-immunoconjugate accumulation and potentiates light-activated photo-immunotoxicity in ovarian cancer and glioblastoma. It is further demonstrated that co-delivery and light activation of BPD and FKR560 allow longitudinal fluorescence tracking of photoimmunoconjugate and nanoparticle in cells. Using xenograft mouse models of epithelial ovarian cancer, intravenous injection of photo-immunoconjugated nanoparticles doubles intratumoral accumulation of photo-immunoconjugates, resulting in an enhanced photoimmunotherapy-mediated tumor volume reduction, compared to "standard" immunoconjugates. This generalizable "carrier effect" phenomenon is attributed to the successful incorporation of photo-immunoconjugates onto a nanoplatform, which modulates immunoconjugate delivery and improves treatment outcomes.

Organochlorine pesticides in soil, air, and vegetation at and around a contaminated site in southwestern China: Concentration, transmission, and risk evaluation.

Remediation and management of contaminated sites have become a prevalent problem under the current situation in China. The present study was conducted to investigate the concentration, transmission, and health risk of organochlorine pesticides (OCPs) in soil, air, and vegetation at and around a typical pesticide-contaminated site located in southwestern China. Exchange flux between soil and air was calculated to investigate the transmission of OCPs. Hexachlorocyclohexane (ΣHCHs, top soil: 19.1 mg/kg d.w., air: 52.3 ng/m3, vegetation: 0.17 mg/kg d.w.) and dichlorodiphenyltrichloroethane (ΣDDTs, top soil: 200 mg/kg d.w., air: 130 ng/m3, vegetation: 0.78 mg/kg d.w.) were the dominant pollutants at the contaminated site. Around the site, the soil, air, and vegetation samples had higher OCP concentrations than those in the normal areas, which were found to be dominated by ΣHCHs (top soil: 129 ng/g d.w., air: 5.09 ng/m3, vegetation: 81.8 ng/g d.w.) and ΣDDTs (top soil: 360 ng/g, air: 7.47 ng/m3, vegetation: 189 ng/g d.w.). The fugacity fractions of OCPs (>0.7) showed a net volatilization from soil into air, indicating that soil is an obvious pollution source for the atmosphere, especially at the site. Through human health risk evaluation, serious carcinogenic risk (CRn) and hazardous index (HIn) were found at the site (CRn: 7.4 × 10-6-1.04 × 10-4, HIn: 0.02 to 8.97) and the nearby areas (CRn: 3.37 × 10-6 for adults and 1.68 × 10-6 for children on average).

Effective Two-Photon Excited Photodynamic Therapy of Xenograft Tumors Sensitized by Water-Soluble Bis(arylidene)cycloalkanone Photosensitizers.

A series of bis(arylidene)cycloalkanone photosensitizers modified by polyethylene glycol (PEG) have been studied for two-photon excited photodynamic therapy (2PE-PDT). As compared with their prototype compounds, these PEGylated photosensitizers show enhanced water solubilities while their photophysical and photochemical properties, including linear absorption, two-photon absorption, fluorescence, and singlet oxygen quantum yield, remain unaltered. In vitro behaviors (cellular uptake, subcellular localization, photocytotoxicity in both PDT and 2PE-PDT) of these photosensitizers reveal that an optimized lipid-water partition coefficient can be obtained by adjusting the length and position of the PEG chains. Among them, the photosensitizer modified asymmetrically by two tetraethylene glycol chains presents the best performance as a 2PE-PDT candidate. Selective blood-vessel closure and obvious therapeutic effect in inhibiting the growth of tumors are confirmed by in vivo 2PE-PDT after intravenous injection of this photosensitiezer. The survival periods of treated tumor-bearing mice are significantly prolonged. This study demonstrates the feasibility of using a simple molecule to construct a potential candidate for 2PE-PDT.