Application of environmental DNA metabarcoding to identify fish community characteristics in subtropical river systems.

Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next-generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream-downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order-/family-level grouping, genus-/species-level grouping could more accurately reveal the differences between upstream zones I-III, midstream zones IV-V, and downstream zones VI-VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring.

Abundance and characteristics of microplastics in the Wanquan River estuary, Hainan Island.

As the nexus where rivers and oceans meet, estuaries are vulnerable to microplastic (MP) pollution derived from rivers. However, few studies have focused on the pollution status of MPs in small estuarine areas. Here, the abundance and characteristics of MPs in surface water and sediment samples from a small estuary, the Wanquan River estuary, were studied. The average abundance of MPs was 6573 ± 2659 n/m3 in surface water and 1065 ± 696 n/kg dw in sediment samples from the Wanquan River estuary. Most of the MPs in water samples and sediments were red (92.9 % and 88.1 %) fragments (87.4 % and 95.5 %) with sizes <1.0 mm (90.8 % and 92.4 %) made up of antifouling paint particles (APPs) (83.5 % and 89.8 %), respectively. A significant positive correlation (p < 0.01) was found between the concentration of Cu2+ and the abundance of APPs in sediment samples from the Wanquan River estuary. The APPs in the sediments can act as a continuous source of toxic chemicals (e.g., Cu2+) to marine environments. The results of this study expand our knowledge about MP pollution in small estuaries, and the ecological risk of APPs in the Wanquan River estuary to aquatic organisms should not be ignored.

Psychometric Properties of the Chinese Translated Athlete Burnout Questionnaire: Evidence From Chinese Collegiate Athletes and Elite Athletes.

The purpose of the study was to translate the athlete burnout questionnaire (ABQ) into Simplified Chinese and examine its psychometric properties in Chinese collegiate athletes and elite athletes. Firstly, the factor structure, internal consistency reliability and nomological validity of the Chinese translated ABQ was examined in a sample of Chinese collegiate athletes (n = 214, 58.9% females). Secondly, abovementioned psychometric properties were examined in a sample of Chinese elite athletes (n = 505, 52.7% females). Finally, measurement invariance of the Chinese translated ABQ was examined across the two samples. It was found that the 12-item three-correlated-factors model outperformed the one factor model and bi-factor model in collegiate athlete sample whereas the 12-item bi-factor model best represented the factor structure of the Chinese translated ABQ in elite athlete sample. Satisfactory internal consistency reliabilities of the Chinese translated ABQ were evidenced in the two samples. Nomological validity was also supported by the results of the two samples that the three subscales of the ABQ were significantly associated with its theoretically related variables. Results of multiple-group confirmatory factor analysis revealed that weak measurement invariance of the Chinese translated ABQ (three-correlated-factors model) was evidenced across the two samples. Collectively, results of this study indicated that the 12-item Chinese translated ABQ could be used for measuring burnout of Chinese collegiate and elite athletes. Significance and implication of the current study as well as recommendations for future study were discussed.

[Distribution and Ecological Risk Assessment of PPCPs in Drinking Water Sources of Henan Province].

The occurrence of emerging pollutants pharmaceuticals and personal care products (PPCPs) in aquatic environments has potential adverse effects on aquatic organisms, and the presence of PPCPs in drinking water sources is very likely to cause harm to human health. The PPCPs pollution in five typical drinking water sources in Henan province was investigated. Moreover, the source of pollutants was analyzed and the relevant ecological risks were evaluated. The results showed that the cumulative concentrations of 20 PPCPs at different sampling sites ranged from 24.2 to 317.6 ng·L-1. Caffeine (CFI) was the highest level contaminant, with the concentration up to 186.4 ng·L-1, followed by sulfamethoxazole (SMX) and ofloxacin (OFC), with detected concentrations up to 70.8 ng·L-1 and 24.2 ng·L-1, respectively. The pollution of PPCPs in Heigangkou drinking water sources was higher than those of other drinking water sources. The comparation of the labile indicator CFI and the conservative indicator carbamazepine (CBZ) concentrations implies that the pollutions from the upstream water and around scattered domestic sewage might be responsible for the PPCPs present in these drinking water sources. The risk quotient (RQ) calculation results indicated that the detected PPCPs in 5 drinking water sources have moderate to high risks to algae, while low to moderate risks to invertebrates and fish. Therefore, attention should be paid to relevant pollution control.

High-power, continuous-wave, phase-locked quantum cascade laser arrays emitting at 8 µm.

We report a room-temperature eight-element phase-locked quantum cascade laser array emitting at 8 µm with a high continuous-wave power of 8.2 W and wall plug efficiency of 9.5%. The laser array operates primarily via the in-phase supermode and has single-mode emission with a side-mode suppression ratio of ~20 dB. The quantum cascade laser active region is based on a high differential gain (8.7 cm/kA) and low voltage defect (90 meV) design. A record high wall plug efficiency of 20.4% is achieved from a low loss buried ridge type single-element Fabry-Perot laser operating in pulsed mode at 20 °C.

Mathematical modeling of simultaneous carbon-nitrogen-sulfur removal from industrial wastewater.

A mathematical model of carbon, nitrogen and sulfur removal (C-N-S) from industrial wastewater was constructed considering the interactions of sulfate-reducing bacteria (SRB), sulfide-oxidizing bacteria (SOB), nitrate-reducing bacteria (NRB), facultative bacteria (FB), and methane producing archaea (MPA). For the kinetic network, the bioconversion of C-N by heterotrophic denitrifiers (NO3-→NO2-→N2), and that of C-S by SRB (SO42-→S2-) and SOB (S2-→S0) was proposed and calibrated based on batch experimental data. The model closely predicted the profiles of nitrate, nitrite, sulfate, sulfide, lactate, acetate, methane and oxygen under both anaerobic and micro-aerobic conditions. The best-fit kinetic parameters had small 95% confidence regions with mean values approximately at the center. The model was further validated using independent data sets generated under different operating conditions. This work was the first successful mathematical modeling of simultaneous C-N-S removal from industrial wastewater and more importantly, the proposed model was proven feasible to simulate other relevant processes, such as sulfate-reducing, sulfide-oxidizing process (SR-SO) and denitrifying sulfide removal (DSR) process. The model developed is expected to enhance our ability to predict the treatment of carbon-nitrogen-sulfur contaminated industrial wastewater.

ROR nuclear receptors: structures, related diseases, and drug discovery.

Nuclear receptors (NRs) are ligand-regulated transcription factors that regulate metabolism, development and immunity. The NR superfamily is one of the major classes of drug targets for human diseases. Retinoic acid receptor-related orphan receptor (ROR) α, ß and γ belong to the NR superfamily, and these receptors are still considered as 'orphan' receptors because the identification of their endogenous ligands has been controversial. Recent studies have demonstrated that these receptors are regulated by synthetic ligands, thus emerge as important drug targets for the treatment of multiple sclerosis, rheumatoid arthritis, psoriasis, etc. Studying the structural basis and ligand development of RORs will pave the way for a better understanding of the roles of these receptors in human diseases. Here, we review the structural basis, disease relevance, strategies for ligand identification, and current status of development of therapeutic ligands for RORs.

Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia.

Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.

Etoricoxib versus indometacin in the treatment of Chinese patients with acute gouty arthritis: a randomized double-blind trial.

BACKGROUND: Acute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China. METHODS: A randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs). RESULTS: Etoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34). CONCLUSIONS: Etoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).

Elementary sulfur in effluent from denitrifying sulfide removal process as adsorbent for zinc(II).

The denitrifying sulfide removal (DSR) process can simultaneously convert sulfide, nitrate and organic compounds into elementary sulfur (S(0)), di-nitrogen gas and carbon dioxide, respectively. However, the S(0) formed in the DSR process are micro-sized colloids with negatively charged surface, making isolation of S(0) colloids from other biological cells and metabolites difficult. This study proposed the use of S(0) in DSR effluent as a novel adsorbent for zinc removal from wastewaters. Batch and continuous tests were conducted for efficient zinc removal with S(0)-containing DSR effluent. At pH<7.5, removal rates of zinc(II) were increased with increasing pH. The formed S(0) colloids carried negative charge onto which zinc(II) ions could be adsorbed via electrostatic interactions. The zinc(II) adsorbed S(0) colloids further enhanced coagulation-sedimentation efficiency of suspended solids in DSR effluents. The DSR effluent presents a promising coagulant for zinc(II) containing wastewaters.

[A study of serum cartilage oligomeric matrix protein and matrix metalloproteinase-3 concentration in osteoarthritic rabbit models].

OBJECTIVE: To study the levels of cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3) in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis (OA). METHODS: The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2, 6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling (at 2, 6 weeks respectively); X ray of model keens was also obtained in different period. Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. RESULTS: (1) Morphological observations:immobilizing the right knees of rabbits in full extension using plaster cast was a reliable method for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritis gradually increased with time extended. (2) The levels of COMP [(3.64 ± 0.18) µg/L], MMP-3 [(1.99 ± 0.81) µg/L] in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP (3.35 ± 0.20) µg/L, MMP-3 (1.61 ± 0.71) µg/L]. The levels of COMP [(3.96 ± 0.44) µg/L], MMP-3 [(3.44 ± 0.91) µg/L] of 6 weeks were much higher, with a significant difference (P < 0.05). The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA (r > 0.710, and P < 0.05). CONCLUSION: The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.

[The safety of hydroxychloroquine in pregnant patients with systemic lupus erythematosus].

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in pregnant patients with systemic lupus erythematosus (SLE). METHODS: Twenty-four pregnant patients with SLE treated with HCQ during pregnancy from May, 2006 to February, 2011 were studied retrospectively. All babies were followed up during early infancy for growth development. RESULTS: Of them, 22 patients were treated with HCQ throughout the whole pregnancy with no lupus flare occurred in 21 patients (95.4%), while temporary discontinuation of HCQ precipitated a flare of disease in two patients. Three patients (12.5%) had premature delivery, and pregnancy induced hypertension happened in 3 patients (12.5%). No congenital abnormalities occurred and mean follow-up of 26 months (range 1 - 47 months) revealed no abnormalities in these children. CONCLUSION: Our findings reinforce the safety of HCQ therapy during pregancy and HCQ should probably be maintained throughout the pregancy in patients with SLE.

[A multicenter, double-blind, placebo-controlled, randomized, phase III clinical study of etanercept in treatment of ankylosing spondylitis].

OBJECTIVE: To evaluate the short-term efficacy and safety of etanercept treatment in Chinese patients with active ankylosing spondylitis (AS). METHODS: This was a 12-week multicenter, double-blind, placebo-controlled, randomized phase III clinical study. The first part was a 6-week placebo-controlled period followed by a 6-week open-label period. The primary efficacy endpoint was the percentage of subjects achieving a 20% improvement in assessment in ankylosing spondylitis (ASAS) (ASAS 20). The secondary efficacy endpoints were the percentage of patients achieving a 40% improvement in ASAS (ASAS 40), achieving a 50% improvement in ASAS (ASAS 50), achieving a 70% improvement in ASAS (ASAS 70), and ASAS 5/6 responses at all visits, and the improvement in subject global assessment, physician global assessment, nocturnal and total back pain, bath AS functional index (BASFI), bath AS disease activity index (BASDAI), spinal mobility, joint assessment and quality of life assessment. All subjects in the study were evaluated for safety. RESULTS: The primary endpoint, ASAS 20 at week 6, was achieved by 86.5% (64/74) patients in the etanercept group compared to 29.5% (23/78) patients in the placebo group (P < 0.001). As early as week 2, the percentages of patients achieving the ASAS 20 between the two groups were significantly different. Furthermore, the majority of secondary efficacy end points were also significantly improved. Most of adverse events (AE) were mild in nature, the commonest adverse events were elevated liver function levels, injection site reactions and nasopharyngitis. No death or serious AE were observed. CONCLUSION: Etanercept can improve symptoms fastly, significantly and safely in Chinese patients with active AS.

[Efficacy and safety of infliximab in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA). METHODS: Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated. RESULTS: After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy. CONCLUSION: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.

[Adalimumab plus methotrexate for the treatment of rheumatoid arthritis: a multi-center randomized, double-blind, placebo-controlled clinical study.].

OBJECTIVE: To investigate the efficacy and safety of adalimumab plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). METHODS: This is a multi-center, randomized, double-blind, parallel-group, and placebo-controlled clinical study, included a total of 302 cases of active rheumatoid arthritis, randomized into three groups of observation: 40 mg adalimumab (121 cases), 80 mg adalimumab (121 cases), or placebo (60 cases). Upon enrollment, all subjects had been previously treated with MTX for at least 3 months, and their doses of drug had remained stable for at least 28 days. The double-blind phase lasted for 12 weeks, during which the subjects were administered with adalimumab or placebo subcutaneously every other week. Then the subjects entered into another 12 weeks of open-label study, which included subcutaneous injection of 40 mg adalimumab every other week. In both the double-blind and the open-label periods, all subjects were maintained concomitantly with MTX that had already been used before this study. The primary efficacy variables were evaluated on basis of American College of Rheumatology (ACR)20 response rate at week 12. The secondary efficacy variables included: ACR20 response rate at week 24; ACR50 and ACR70 response rates at weeks 12 and 24; and changes at weeks 12 and 24 compared with baseline observations for tender and swollen joint counts, as well as the assessment of pain with visual analog scale (VAS), the physician's and the patient's global assessment of disease activity (VAS), and the analysis on health assessment questionnaire (HAQ) and health related quality of life (HRQL) measured by Short Form-36 (SF-36); The safety variables mainly included adverse events (AE). RESULT: During the double-blind period, subjects treated with 40 mg of adalimumab, 57.0% achieved ACR20 response at week 12 (P = 0.004 versus placebo), and subjects treated with 80 mg of adalimumab, 51.2% achieved ACR20 response at week 12 (P = 0.026 versus placebo), and only 35.0% of subjects treated with placebo achieved ACR20 response at week 12. On the other hand, 32.2% of subjects receiving 40 mg of adalimumab achieved ACR50 response (P = 0.009 versus placebo), and 15.7% achieved ACR70 response (P = 0.007 versus placebo) at week 12. Subjects treated with 40 mg of adalimumab got a better result versus placebo at week 12 for tender joint count, swollen joint count, and improvement in C-reactive protein; and subjects treated with 80 mg of adalimumab were also seen an amelioration versus placebo at week 12 for swollen joint count, and improvement in C-reactive protein; all of these findings were statistically significant in differences. During the open-label period all subjects received 40 mg of adalimumab, and response rates for ACR20, ACR50, and ACR70 in the two treatment groups of 40 mg and 80 mg adalimumab were maintained or improved from week 12 to week 24 (being 73.1%, 40.3% and 17.6% respectively for 40 mg group; 71.1%, 39.5% and 17.5% respectively for 80 mg group); while response in the original placebo group (being 67.8%, 44.1% and 18.6%) increased during the 12-week open-label period to match that of the original adalimumab treatment groups. While for changes in tender and swollen joint counts, VAS, HAQ, SF-36, a significant improvement was seen at week 24 when compared with baseline and week 12 values. Throughout the double-blind and open-label period, adverse events reported in >/= 5% of subjects at least possibly associated with the study drug were upper respiratory tract infection, nasopharyngitis, and injection site itching, mostly being mild to moderate in severity. There were 3 cases of tuberculosis reported during this study. And 3 cases of serious adverse event (SAE) were reported among the adalimumab subjects during the double-blind period, which were determined as unrelated or probably unrelated to the study drug. And 8 cases (2.7%) of SAE were seen among the adalimumab subjects during the open-label period, 3 of which were at least possibly unrelated with the study drug. All SAEs reported were consistent to those seen in other adalimumab trials. No other unexpected safety signals were reported. CONCLUSION: Adalimumab plus MTX is better than single MTX in efficacy for the treatment of RA. Being generally safe and well tolerated, adalimumab plus MTX can significantly increase the response rate, continuously reduce the arthritic signs, symptoms and the inflammatory factors in patients, and also be helpful for reducing disabilities and improving the global quality of life for the patients.

Evaluation of efficacy and safety of diacerein in knee osteoarthritis in Chinese patients.

OBJECTIVE: To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). METHODS: A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. RESULTS: Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians' overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P > 0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P < 0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P < 0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P < 0. 001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. CONCLUSIONS: Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.

Isolation and Characterization of the PA28-associated Proteasome.

Proteasome, a high molecular weight multicatalytic protease complex,is responsible for most non-lysosomal intracellular protein degradations. The proteasome is composed of a 20 S catalytic core (20 S proteasome) and additional subunits, that are thought to be involved in the recognition of proteins or in the regulation of the protease activity of the proteasome. A 180 kD activator, named PA28 or Reg, associates with the 20 S proteasome and enhance the peptidase activity of the 20 S core enzyme. In this report, the biochemical isolation of the PA28-associated proteasome subset from the 20 S proteasome core is described, based on gradient anion exchange chromatography. The PA28-20 S proteasome subset, isolated from EBV-transformed B cells, was found to be highly enriched in the LMP2 (low molecular weight protein) subset, whereas no LMP2 was detected by immunoblotting in the PA28-20 S proteasome subset. The close correlation of expression of PA28 and LMP2, two interferon (IFN)-gamma inducible proteasome components,on a single proteasome subset suggests that PA28 may associate preferentially with LMP2-containing proteasomes, and/or this subset may have a specific role in the processing of environmental antigens.