Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

Digital adherence technologies to improve tuberculosis treatment outcomes in China: a cluster-randomised superiority trial.

BACKGROUND: Drug-sensitive tuberculosis treatment requires 6 months of therapy, so adherence problems are common. Digital adherence technologies might improve tuberculosis treatment outcomes. We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes. METHODS: We did a cluster-randomised superiority trial across four prefectures in China. 24 counties or districts (clusters) were randomly assigned (1:1) to intervention or control groups. We enrolled patients aged 18 years or older with GeneXpert-positive, rifampicin-sensitive pulmonary tuberculosis, who were receiving daily fixed-dose combination treatment. Patients in the intervention group received a medication monitor for daily drug-dosing reminders, monthly review of adherence data by health-care provider, and management of poor adherence; and patients in the control group received routine care (silent-mode monitor-measured adherence). Only the independent endpoints review committee who assessed endpoint data for some participants were masked to study group assignment. Patients were followed up (with sputum solid culture) at 12 and 18 months. The primary outcome was a composite of death, loss to follow-up, treatment failure, switch to multidrug-resistant tuberculosis treatment, or tuberculosis recurrence by 18 months from treatment start, analysed in the intention-to-treat population. Analysis accounted for study design with multiple imputation for the primary outcome. This trial is now complete and is registered with ISRCTN, 35812455. FINDINGS: Between Jan 26, 2017, and April 3, 2019, 15 257 patients were assessed for eligibility and 3074 were enrolled, 2686 (87%) of whom were included in the intention-to-treat population. 1909 (71%) of 2686 patients were male, 777 (29%) were female, and the median age was 44 years (IQR 29-58). By 18 months from treatment start, using multiple imputation for missing outcomes, 239 (16% [geometric mean of cluster-level proportion]) of 1388 patients in the control group and 224 (16%) of 1298 in the intervention group had a primary composite outcome event (289 [62%] of 463 events were loss to follow-up during treatment and 42 [9%] were tuberculosis recurrence). The intervention had no effect on risk of the primary composite outcome (adjusted risk ratio 1·01, 95% CI 0·73-1·40). INTERPRETATION: Our digital medication monitor intervention had no effect on unfavourable outcomes, which included loss to follow-up during treatment, tuberculosis recurrence, death, and treatment failure. There was a failure to change patient management following identification of treatment non-adherence at monthly reviews. A better understanding of adherence patterns and how they relate to poor outcomes, coupled with a more timely review of adherence data and improved implementation of differentiated care, may be required. FUNDING: Bill & Melinda Gates Foundation.

Ancient DNA reveals potentially toxic cyanobacteria increasing with climate change.

Cyanobacterial blooms in freshwater systems are a global threat to human and aquatic ecosystem health, exhibiting particularly harmful effects when toxin-producing taxa are present. While climatic change and nutrient over-enrichment control the global expansion of total cyanobacterial blooms, it remains unknown to what extent this expansion reflected cyanobacterial assemblage due to the scarcity of long-term monitoring data. Here we use high-throughput sequencing of sedimentary DNA to track ∼100 years of changes in cyanobacterial community in hyper-eutrophic Lake Taihu, China's third largest freshwater lake and the key water source for ∼30 million people. A steady increase in the abundance of Microcystis (as potential toxin producers) during the past thirty years was correlated with increasing temperatures and declining wind speeds, but not with temporal trends in lakewater nutrient concentrations, highlighting recent climate effects on potentially increasing toxin-producing taxa. The socio-environmental repercussions of these findings are worrisome as continued anthropogenic climate change may counteract nutrient amelioration efforts in this critical freshwater resource.

Two-Dimensional Transition Metal-Hexaaminobenzene Monolayer Single-Atom Catalyst for Electrocatalytic Carbon Dioxide Reduction.

Electrocatalytic reduction of CO2 to valuable fuels and chemicals can not only alleviate the energy crisis but also improve the atmospheric environment. The key is to develop electrocatalysts that are extremely stable, efficient, selective, and reasonably priced. In this study, spin-polarized density function theory (DFT) calculations were used to comprehensively examine the catalytic efficacy of transition metal-hexaaminobenzene (TM-HAB) monolayers as single-atom catalysts for the electroreduction of CO2. In the modified two-dimensional TM-HAB monolayer, our findings demonstrate that the binding of individual metal atoms to HAB can be strong enough for the atoms to be evenly disseminated and immobilized. In light of the conflicting hydrogen evolution processes, TM-HAB effectively inhibits hydrogen evolution. CH4 dominates the reduction byproducts of Sc, Ti, V, Cr, and Cu. HCOOH makes up the majority of Zn's reduction products. Co's primary reduction products are CH3OH and CH4, whereas Mn and Fe's primary reduction products are HCHO, CH3OH, and CH4. Among these, the Ti-HAB reduction products have a 1.14 eV limiting potential and a 1.31 V overpotential. The other monolayers have relatively low overpotentials between 0.01 V and 0.7 V; therefore, we predict that TM-HAB monolayers will exhibit strong catalytic activity in the electrocatalytic reduction of CO2, making them promising electrocatalysts for CO2 reduction.

Study of Water- and Organic-Soluble Extracts from Trichosanthes on Type 1 Diabetes Mellitus.

This study investigates the effects of the water-soluble and organic-soluble Trichosanthes extracts on the hyperglycemic condition in streptozotocin- (STZ-) induced diabetic rats. The blood glucose levels, body weights, water intake, and urine volumes of rats in different experimental groups were monitored throughout the experiment, and the results obtained indicate that the two extracts can effectively reduce blood sugar levels, increase body weights, and improve water intake and urine volumes in diabetic rats. Based on blood biochemical analyses, the two extracts play an important role in regulating the diabetes-induced lipid metabolism disorder, increasing the levels of insulin and C-peptide, and alleviating the symptoms of diabetes. The variation in the liver glycogen contents of the water-soluble fraction and ethanol fraction groups suggests that the mechanisms underlying the hypoglycemic effects of the two extracts are different. Indeed, the water-soluble fraction alleviates diabetes symptoms in rats mainly by antioxidative activity, unlike the ethanol fraction.

BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis.

Lung adenocarcinoma (LUAD) is one of the most common causes of cancer death in men. BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) has been reported to contribute to the initiation and development of several cancers. Here, we aimed to explore the potential role of BUB1B in LUAD. We found BUB1B was upregulated in LUAD, suggesting its potential role as a biomarker for LUAD diagnosis. Significantly, LUAD patients with high BUB1B expression had a shorter survival time than those with low BUB1B expression. Knocking-out BUB1B resulted in suppression of cell proliferation, migration, and invasion in vitro, and inhibition of tumor growth in the xenograft experiment. Further analysis revealed that BUB1B regulates glycolysis in LUAD and interacting with ZNF143 in LUAD cells. The interaction was demonstrated by silencing ZNF143, which led to a decrease in proliferation, migration, and invasion in LUAD cells, whereas overexpressing BUB1B had the opposite effects. Our study suggested that the ZNF143/BUB1B axis plays a pivotal role in LUAD progression, which might be a potential target for LUAD management.

Effect of using electronic medication monitors on tuberculosis treatment outcomes in China: a longitudinal ecological study.

BACKGROUND: In China, an indigenously developed electronic medication monitor (EMM) was designed and used in 138 counties from three provinces. Previous studies showed positive results on accuracy, effectiveness, acceptability, and feasibility, but also found some ineffective implementations. In this paper, we assessed the effect of implementation of EMMs on treatment outcomes. METHODS: The longitudinal ecological method was used at the county level with aggregate secondary programmatic data. All the notified TB cases in 138 counties were involved in this study from April 2017 to June 2019, and rifampicin-resistant cases were excluded. We fitted a multilevel model to assess the relative change in the quarterly treatment success rate with increasing quarterly EMM coverage rate, in which a mixed effects maximum likelihood regression using random intercept model was applied, by adjusting for seasonal trends, population size, sociodemographic and clinical characteristics, and clustering within counties. RESULTS: Among all 69 678 notified TB cases, the treatment success rate was slightly increased from 93.5% [95% confidence interval (CI): 93.0-94.0] in second quarter of 2018 to 94.9% (95% CI: 94.4-95.4) in second quarter of 2019 after implementing EMMs. There was a statistically significant effect between quarterly EMM coverage and treatment success rate after adjusting for potential confounders (P = 0.0036), increasing 10% of EMM coverage rate will lead to 0.2% treatment success rate augment. Besides, an increase of 10% of elderly or bacteriologically confirmed TB will lead to a decrease of 0.4% and 0.9% of the treatment success rate. CONCLUSIONS: Under programmatic settings, we found a statistically significant effect between increasing coverage of EMM and treatment success rate at the county level. More prospective studies are needed to confirm the effect of using EMM on TB treatment outcomes. We suggest performing operational research on EMMs that provides real-time data under programmatic conditions in the future.

Nitrogen-doped nanoporous graphene induced by a multiple confinement strategy for membrane separation of rare earth.

Rare earth separation is still a major challenge in membrane science. Nitrogen-doped nanoporous graphene (NDNG) is a promising material for membrane separation, but it has not yet been tested for rare earth separation, and it is limited by multi-complex synthesis. Herein, we developed a one-step, facile, and scalable approach to synthesize NDNG with tunable pore size and controlled nitrogen content using confinement combustion. Nanoporous hydrotalcite from Zn(NO3)2 is formed between layers of graphene oxide (GO) absorbed with phenylalanine via confinement growth, thus preparing the sandwich hydrotalcite/phenylalanine/GO composites. Subsequently, area-confinement combustion of hydrotalcite nanopores is used to etch graphene nanopores, and the hydrotalcite interlayer as a closed flat nanoreactor induces two-dimensional space confinement doping of planar nitrogen into graphene. The membrane prepared by NDNG achieves separation of Sc3+ from the other rare earth ions with excellent selectivity (∼3.7) through selective electrostatic interactions of pyrrolic-N, and separation selectivity of ∼1.7 for Tm3+/Sm3+.

Highly Selective Separation of Rare Earth Elements by Zn-BTC Metal-Organic Framework/Nanoporous Graphene via In Situ Green Synthesis.

Rare earth elements (REEs) are used widely in devices of many fields, but it is still a troublesome task to achieve their selective separation and purification. Metal-organic frameworks (MOFs) as an emerging porous crystalline material have been used for selective separation of REEs using the size-selective crystallization properties. However, so far, almost all MOFs cannot be used directly for selective separation of REEs in strong acid via solid-state adsorption. Herein, a zinc-trimesic acid (Zn-BTC) MOF is grown by solid synthesis in situ on ZnO nanoparticles covering nanoporous graphene for preparing Zn-BTC MOF/nanoporous graphene composites with strong acid resistance. The adsorption capacity of the resulting composites to REEs is highly sensitive to the ionic radius, which may be attributed to the fact that the REE ions coordinate with O to form a stable structure. The selectivity of Ce/Lu is ≈10,000, and it is extremely important that the selectivity between adjacent REEs (e.g., Nd/Pr) is as high as ≈9.8, so the composite exhibits the best separation performance so far. This work provides a green, facile, scale, and effective synthesis strategy of Zn-BTC MOF/nanoporous graphene, which is hopefully applied directly in the separation industries of REEs.

Circ-CCS is identified as a cancer-promoting circRNA in lung cancer partly by regulating the miR-383/E2F7 axis.

BACKGROUND: Increasing biomolecules have been found to be involved in the lung cancer development. This study will perform the function and mechanism analyses of a novel circular RNA copper chaperone for superoxide dismutase (circ-CCS) in lung cancer. METHODS: Circ-CCS, microRNA-383 (miR-383) and E2F transcription factor 7 (E2F7) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was detected using Cell Counting Kit-8 (CCK-8). Clonal ability was measured by colony formation assay. Cell apoptosis was determined via flow cytometry. Cell migration and invasion were assessed by transwell assay. Detection of protein was completed using western blot. Xenograft assay was used for the functional analysis of circ-CCS in vivo. The binding between targets was proved by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. E2F7 protein level was also examined by Immunohistochemistry (IHC) analysis in human tissues. RESULTS: Circ-CCS was upregulated in lung cancer and could predict poor prognosis. Downregulation of circ-CCS inhibited lung cancer cell growth and metastasis while promoted apoptosis in vitro, and suppressed tumorigenesis of lung cancer in vivo. Circ-CCS had sponge effect on miR-383 and the function of si-circ-CCS was achieved by upregulating miR-383. E2F7 was a target gene of miR-383 and its downregulation was responsible for the anti-cancerous role of miR-383 in lung cancer. Circ-CCS could elevate E2F7 expression via interacting with miR-383. CONCLUSION: Circ-CCS was shown to facilitate lung cancer progression via the miR-383/E2F7 axis, exhibiting the pivotal value of circ-CCS in diagnosis and treatment of lung cancer.

Excessive nitrogen addition accelerates N assimilation and P utilization by enhancing organic carbon decomposition in a Tibetan alpine steppe.

High amounts of deposited nitrogen (N) dramatically influence the stability and functions of alpine ecosystems by changing soil microbial community functions, but the mechanism is still unclear. To investigate the impacts of increased N deposition on microbial community functions, a 2-year multilevel N addition (0, 10, 20, 40, 80 and 160 kg N ha-1 year-1) field experiment was set up in an alpine steppe on the Tibetan Plateau. Soil microbial functional genes (GeoChip 4.6), together with soil enzyme activity, soil organic compounds and environmental variables, were used to explore the response of microbial community functions to N additions. The results showed that the N addition rate of 40 kg N ha-1 year-1 was the critical value for soil microbial functional genes in this alpine steppe. A small amount of added N (≤40 kg N ha-1 year-1) had no significant effects on the abundance of microbial functional genes, while high amounts of added N (>40 kg N ha-1 year-1) significantly increased the abundance of soil organic carbon degradation genes. Additionally, the abundance of microbial functional genes associated with NH4+, including ammonification, N fixation and assimilatory nitrate reduction pathways, was significantly increased under high N additions. Further, high N additions also increased soil organic phosphorus utilization, which was indicated by the increase in the abundance of phytase genes and alkaline phosphatase activity. Plant richness, soil NO2-/NH4+ and WSOC/WSON were significantly correlated with the abundance of microbial functional genes, which drove the changes in microbial community functions under N additions. These findings help us to predict that increased N deposition in the future may alter soil microbial functional structure, which will lead to changes in microbially-mediated biogeochemical dynamics in alpine steppes on the Tibetan Plateau and will have extraordinary impacts on microbial C, N and P cycles.

Do electronic medication monitors improve tuberculosis treatment outcomes? Programmatic experience from China.

BACKGROUND: In China, an indigenously developed electronic medication monitor (EMM) was used. EMM recorded each time the device was opened (no real time data), offering an indirect measure of tuberculosis treatment adherence. Previous study in China showed that the EMM uptake was satisfactory, missing adherence data were common in the information management system (25%) and shift to directly observed therapy (DOT) based on poor adherence documented by EMMs were seldom. OBJECTIVES: Among people with tuberculosis notified in 30 counties (July-December 2018) where EMM supported self-administered therapy (SAT) was suggested to all eligible (no communication impairment, ambulatory), we assessed the relative differences in unfavourable outcomes and deaths among those started on EMM at baseline (within first month of diagnosis) when compared to SAT alone. METHODS: This was a cohort study using secondary data. We employed an intention to treat analysis, and used modified Poisson regression with robust variance estimates to assess the association. RESULTS: Of 1810 eligible people, 1047 used EMM at baseline and of them, 216 (20.1%) stopped using EMM midway. Of 763 people who did not use EMM at baseline, 267 (35.0%) started using EMM later during the treatment. Among those who started using EMM at baseline, 6.3% [95% CI: 4.9, 8.0] had unfavourable outcomes compared to 6.7% [95% CI: 5.1, 8.8] among those who did not (p = 0.746). Lesser deaths were observed in people who started EMM at baseline when compared to those who did not: 2.5% [95% CI: 1.7, 3.7] versus 3.5% [95% CI: 2.4, 5.2], p = 0.191. The lack of association remained after adjusting for potential confounders (occupation, TB classification and TB category). CONCLUSION: Under programmatic settings, we did not find significant differences in the outcomes. Optimization of EMMs by shifting to DOT when indicated, addressing the issue of missing data and ensuring continuous use is required.

Electronic medication monitor for people with tuberculosis: Implementation experience from thirty counties in China.

BACKGROUND: China piloted a digital adherence technology called electronic medication monitor (EMM) to support self-administered treatment for tuberculosis. EMM is a portable plastic box that records each time the device is opened, offering an indirect measure of treatment adherence. During the monthly patient visits to tuberculosis designated hospitals, the doctors access the data from the EMM. OBJECTIVES: Among people with tuberculosis notified in 30 counties in China (July-December 2018) where EMM supported self-administered treatment was suggested to all those eligible (no communication impairment, ambulatory care), we assessed the i) proportion eligible for using EMM ii) uptake of EMM and factors associated and iii) treatment adherence, including the proportion shifted to DOT. METHODS: This was an observational study using secondary programme data. Single instance of ≥50% or continued instance of 20-49% monthly missed doses was the eligibility criteria to shift to DOT. We used log binomial regression to identify factors associated with not using EMM within first month. RESULTS: Of 2227 with EMM eligibility data, 1810 (81%) were eligible for EMM. Of 1810 people, 1314 (73%) ever used EMM anytime during treatment, among them, 134 (10%) were eligible for shift to DOT (based on EMM data), and 29 (22%) were shifted. In addition, 70 were shifted while the EMM data was missing. Of 1047 people who started using EMM within first month, we observed 6381 person-months of follow up and there were 1526(25%) instances of missing EMM data. Children (<15 years), elderly (≥65 years), semi-skilled or unemployed people, people with tuberculosis pleurisy and previous tuberculosis treatment were less likely to use EMM within first month. CONCLUSION: The EMM uptake was satisfactory but shift to DOT has to be ensured based on adherence data from EMM. The subsequent follow-up action when EMM data is missing has to be clarified in the guidelines.

Associations between interleukin-10 gene polymorphisms and systemic lupus erythematosus risk: a meta-analysis with trial sequential analysis.

OBJECTIVES: Interleukin-10 (IL-10) polymorphisms have been reported to be associated with systemic lupus erythematosus (SLE), however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations. METHODS: Eligible studies were retrieved by searching PubMed, Embase, Google Scholar, VIP, Wan Fang and China National Knowledge Infrastructure databases. Hardy-Weinberg equilibrium (HWE) was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was evaluated by Q statistic and I2 statistic. Sensitivity analysis and subgroup analysis (stratified by HWE, region, event sample size, source of controls, genotyping method) were conducted and the potential for publication bias was assessed. Trial sequential analysis was introduced to assess the information size and the positive results. RESULTS: Twenty case-control studies were included. Overall results from IL10-1082A/G polymorphism showed increased risk of systemic lupus erythematosus, but no significant associations were observed in both IL10-819C/T and IL10-592C/A polymorphism. Increased risk of SLE was also observed in IL10A/G polymorphism in Asian population, hospital-based and PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) subgroups. In addition, decreased risk of SLE was widely detected in IL10-819C/T and IL10-592C/A polymorphisms in subgroup analysis. CONCLUSIONS: Our study suggests that the IL10-1082A/G polymorphism is a risk factor in systemic lupus erythematosus. A decreased risk of SLE in the IL10-819C/T and IL10-592C/A polymorphisms in subgroups was also observed, but further rigorously studies are needed to confirm these results.

SHCBP1 is a novel target and exhibits tumor­promoting effects in gastric cancer.

The present study investigated the expression and potential influence of SHC SH2 domain­binding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC­803 and SGC­7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4­cyclin D1 cascade and suppressed caspase­3, caspase PARP­dependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumor­promoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC.

Vitamin D status of tuberculosis patients with diabetes mellitus in different economic areas and associated factors in China.

BACKGROUND: Vitamin D could be a mediator in the association between tuberculosis (TB) and diabetes mellitus (DM). A large scale multi-center study confirmed that TB patients with DM had significantly lower serum vitamin D level compared with those without DM and reported that DM was a strong independent risk factor for vitamin D deficiency. OBJECTIVES: This study was undertaken to determine amongst patients with both TB and DM living in different economically defined areas in China: i) their baseline characteristics, ii) their vitamin D status and iii) whether certain baseline characteristics were associated with vitamin D deficiency. METHODS: In DM-TB patients consecutively attending seven clinics or hospitals, we measured 25 hydroxycholecalciferol at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using chi square test and multivariate logistic regression. RESULTS: There were 178 DM-TB patients that included 50 from economically well-developed areas, 103 from better-off areas and 25 from a poverty area. Median vitamin D levels in well-developed, better-off and poverty areas were 11.5ng/ml, 12.2ng/ml and 11.5ng/ml respectively. Amongst all patients, 149 (84%) had vitamin D deficiency-91 (51%) with vitamin D deficiency (10-19.9 ng/ml) and 58 (33%) with severe deficiency (< 10 ng/ml). There was a significantly higher proportion with vitamin D deficiency in the poverty area. The adjusted odds of vitamin D deficiency (25-(OH)D3 <20 ng/ml) were significantly higher in those with longer history of DM (P = 0.038) and with HbA1c≥10% (P = 0.003). CONCLUSION: Over 80% of TB patients with DM in China were vitamin D deficient, with risk factors being residence in a poverty area, a long duration of DM and uncontrolled DM. TB programme managers and clinicians need to pay more attention to the vitamin D status of their patients.

Treatment with IL-19 improves locomotor functional recovery after contusion trauma to the spinal cord.

BACKGROUND AND PURPOSE: IL-19 skews the immune response towards a Th2 type and appears to stimulate angiogenesis. In the current study, we tested if IL-19 treatment could reduce secondary injury and improve functional recovery after contusion spinal cord injury (SCI). EXPERIMENTAL APPROACH: Firstly, mice were given a moderate-severe thoracic SCI at the T9-10 level and expression of IL-19 and its receptor was measured in the injured spinal cord. Then SCI mice were treated with mouse recombinant IL-19 and its blocking antibody to investigate the therapeutic effect of IL-19. KEY RESULTS: Protein expression of IL-19 and its receptor IL-20R1 and IL-20R2 was up-regulated in the injured spinal cord of mice. IL-19 treatment promoted the recovery of locomotor function dose-dependently and reduced loss of motor neurons and microglial and glial activation following SCI. Treatment of SCI mice with IL-19 attenuated macrophage accumulation, reduced protein levels of TNF-α and CCL2 and promoted Th2 response and M2 macrophage activation in the injured region. Treatment of SCI mice with IL-19 promoted angiogenesis through up-regulating VEGF in the injured region. Treatment of SCI mice with IL-19 up-regulated HO-1 expression and decreased oxidative stress in the injured region. The beneficial effect of IL-19 was abolished by coadministration of the blocking antibody. Additionally, IL-19 deficiency in mice delayed the recovery of locomotor function following SCI. CONCLUSIONS AND IMPLICATIONS: IL-19 treatment reduced secondary injuries and improved locomotor functional recovery after contusion SCI, through diverse mechanisms including immune cell polarization, angiogenesis and anti-oxidative responses.

Multicenter evaluation of membrane-based smear microscopy for detecting acid-fast bacilli in China.

OBJECTIVE: To assess the feasibility and reliability of using membrane-based smear microscopy at peripheral laboratories in China. METHODS: The clinical case control study was conducted in five tuberculosis (TB) dispensaries from September 2014 to May 2016. The membrane-based microscopy and direct smear microscopy were performed to compare the sensitivity, specificity, and the examination time for both methods was also analyzed. RESULTS: A total of 5359 TB suspects were consecutively enrolled from 5 TB dispensaries, and 9915 specimens were finally analyzed. The sensitivity for membrane-based microscopy and direct smear microscopy was 76.9% (95% CI, 75.4-78.4) and 53.8% (95% CI, 52.1-55.6) respectively, and the specificity was 96.8% (95% CI, 96.4-97.2) and 99.2% (95% CI, 99.0-99.4) respectively. The sensitivity and specificity were both significantly different (P<0.001) between the two methods. The examination time for membrane-based smear microscopy (209.1±112.0 seconds) was significantly shorter than that for direct smear microscopy (253.1±79.4 seconds) (P<0.05). CONCLUSIONS: Membrane-based smear microscopy showed higher sensitivity and a shorter examination time in comparison with direct smear microscopy and it could be used at peripheral laboratories in China.

Calculation of Thallium's toxicity coefficient in the evaluation of potential ecological risk index: A case study.

As a common pollutive metal element, Tl is very biotoxic. The potential ecological risk index (RI) proposed by Håkanson is one of the commonest methods for evaluation of ecological risk of a metal in sedimentary environment of a water body. According to the calculation principle proposed by Håkanson, the toxicity coefficient of Tl was calculated, and determined as 10 in this paper. In addition, the environmental risk of Tl in the surface sediment of the Beijing-Hangzhou Grand Canal (Zaozhuang Section) was evaluated by RI method, enrichment factor method, etc. The South-to-North Water Diversion Project which benefits four billion people is the largest inter-basin water transfer project in China. The Zaozhuang Section is a significant water conveyance line of this project. We found that the Tl concentrations were 0.46-0.70 µg g-1 with the mean value of 0.61 µg g-1 and were higher than the local background value. The highest contents of Tl occurred in the middle of Zaozhuang section and Tai'erzhuang District, but the enrichment degree of it was much higher in the entrance of Nansihu Lake. The grain size and Al oxides/hydroxides were main factors which controlled the distribution of Tl. Analysis of enrichment factors indicated that Tl in sediments possessed obvious source of human activities which were mainly from combustion of fossil fuels such as coal and mining of mineral resources. As a whole, however, the research region has low Tl content, so Tl has a small probability of environmental pollution.