Photocatalytic Pyridine Synthesis with Enaminones and TMEDA under Metal-Free Conditions.

Reported herein is a new photocatalytic annulation for the synthesis of 2,3,4,6-tetrasubstituted pyridines with enaminones and N,N,N',N'-tetramethyl ethylenediamine (TMEDA). The photocatalytic reactions take place without requiring a transition metal reagent and provide products with broad scope. The methyl in TMEDA acts as the carbon source in pyridine ring construction, and BrCF2CO2Et plays the role of the terminal oxidant for free radical quenching.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Analysis of anatomic location of burns inpatients in China from 2009 to 2018.

BACKGROUND: Burns cause serious physical and psychological harm to patients, placing a heavy burden on the global healthcare system. Our previous study detailed the epidemiological characteristics of burn injuries in Chinese inpatients from 2009 to 2018. Interestingly, the anatomic locations of burn injuries vary by gender, age, provinces, and outcomes among different causes. Therefore, this current study aims to analyze the characteristics of burn injuries in inpatients with various burn sites by collecting data in China from 2009 to 2018. This analysis will inform future healthcare system decisions and provide effective strategies. METHODS: Burns inpatients from 196 hospitals across 31 provinces in China were included in the study, covering the period from 2009 to 2018. The data collected encompassed information on gender, age, etiology, regions, clinical outcomes, and anatomical locations of the injuries. Data analysis was conducted using Microsoft Excel 2007. RESULTS: From 2009 to 2018, a total of 333,995 burns inpatients were recorded. The most vulnerable parts to burns were multiple burn sites (230,090, 68.89%). Women were more susceptible to lower limb burns (15,608, 14%), while men were more prone to eye injuries (8,387, 3.37%) and hand burns (6,119, 2.75%). The age group of 0-10 years was the most vulnerable to burns across all body areas, including internal organs. In China, individuals aged 20-50 years were at a higher risk of head and neck burns compared to other age groups. The Han population showed increased vulnerability to eye injuries (2.12 times higher than minorities), respiratory tract issues (2.09 times higher than minorities), and trunk burns (1.83 times higher than minorities), while being less susceptible to internal organ injuries (0.23 times fewer than minorities) and lower limb burns (0.78 times fewer than minorities). The southwest region had the highest proportion of burns inpatients with burns affecting single body parts, whereas the eastern area had the highest rates of respiratory tract burns (0.85%) and multiple burn sites (80.64%). Scalding was identified as the most common cause of burns, while flame burns (769, 55.81%) and chemical burns (438, 47.35%) were the main causes of respiratory tract and internal organ injuries, respectively. CONCLUSIONS: This study provides an initial description of characteristics of burns inpatients with various anatomic locations of burns in China over the past decade. Our findings will contribute to the most up-to-date clinical evidence database for healthcare planning and prevention initiatives in both China and other countries.

Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

Application of SARIMA model in forecasting and analyzing inpatient cases of acute mountain sickness.

BACKGROUND: Acute Mountain Sickness (AMS) is typically triggered by hypoxia under high altitude conditions. Currently, rule of time among AMS inpatients was not clear. Thus, this study aimed to analyze the time distribution of AMS inpatients in the past ten years and construct a prediction model of AMS hospitalized cases. METHODS: We retrospectively collected medical records of AMS inpatients admitted to the military hospitals from January 2009 to December 2018 and analyzed the time series characteristics. Seasonal Auto-Regressive Integrated Moving Average (SARIMA) was established through training data to finally forecast in the test data set. RESULTS: A total of 22 663 inpatients were included in this study and recorded monthly, with predominant peak annually, early spring (March) and mid-to-late summer (July to August), respectively. Using the training data from January 2009 to December 2017, the model SARIMA (1, 1, 1) (1, 0, 1) 12 was employed to predict the test data from January 2018 to December 2018. In 2018, the total predicted value after adjustment was 9.24%, less than the actual value. CONCLUSION: AMS inpatients have obvious periodicity and seasonality. The SARIMA model has good fitting ability and high short-term prediction accuracy. It can help explore the characteristics of AMS disease and provide decision-making basis for allocation of relevant medical resources for AMS inpatients.

Biomechanical properties of lumbar vertebral ring apophysis cage under endplate injury: a finite element analysis.

OBJECTIVE: This study aimed to compare the biomechanical properties of lumbar interbody fusion involving two types of cages. The study evaluated the effectiveness of the cage spanning the ring apophysis, regardless of the endplate's integrity. METHODS: A finite element model of the normal spine was established and validated in this study. The validated model was then utilized to simulate Lateral Lumbar Interbody Fusion (LLIF) with posterior pedicle screw fixation without posterior osteotomy. Two models of interbody fusion cage were placed at the L4/5 level, and the destruction of the bony endplate caused by curetting the cartilaginous endplate during surgery was simulated. Four models were established, including Model 1 with an intact endplate and long cage spanning the ring apophysis, Model 2 with endplate decortication and long cage spanning the ring apophysis, Model 3 with an intact endplate and short cage, and Model 4 with endplate decortication and short cage. Analyzed were the ROM of the fixed and adjacent segments, screw rod system stress, interface stress between cage and L5 endplate, trabecular bone stress on the upper surface of L5, and intervertebral disc pressure (IDP) of adjacent segments. RESULTS: There were no significant differences in ROM and IDP between adjacent segments in each postoperative model. In the short cage model, the range of motion (ROM), contact pressure between the cage and endplate, stress in L5 cancellous bone, and stress in the screw-rod system all exhibited an increase ranging from 0.4% to 79.9%, 252.9% to 526.9%, 27.3% to 133.3%, and 11.4% to 107%, respectively. This trend was further amplified when the endplate was damaged, resulting in a maximum increase of 88.6%, 676.1%, 516.6%, and 109.3%, respectively. Regardless of the integrity of the endplate, the long cage provided greater support strength compared to the short cage. CONCLUSIONS: Caution should be exercised during endplate preparation and cage placement to maintain the endplate's integrity. Based on preoperative X-ray evaluation, the selection of a cage that exceeds the width of the pedicle by at least 5 mm (ensuring complete coverage of the vertebral ring) has demonstrated remarkable biomechanical performance in lateral lumbar interbody fusion procedures. By opting for such a cage, we expect a reduced occurrence of complications, including cage subsidence, internal fixation system failure, and rod fracture.

Life history traits of low-toxicity alternative bisphenol S on Daphnia magna with short breeding cycles: A multigenerational study.

Due to relatively lower toxicity, bisphenol S (BPS) has become an alternative to previously used bisphenol A. Nevertheless, the occurrence of BPS and its ecological impact have recently attracted increasing attentions because the toxicology effect of BPS with life cycle or multigenerational exposure on aquatic organisms remains questionable. Herein, Daphnia magna (D. magna) multigenerational bioassays spanning four generations (F0-F3) and single-generation recovery (F1 and F3) in clean water were used to investigate the ecotoxicology of variable chronic BPS exposure. For both assays, four kinds of life-history traits (i.e., survival, reproduction, growth and ecological behavior) were examined for each generation. After an 18-day exposure under concentration of 200 µg/L, the survival rate of D. magna was less than 15 % for the F2 generation, whereas all died for the F3 generation. With continuous exposure of four generations of D. magna at environmentally relevant concentrations of BPS (2 µg/L), inhibition of growth and development, prolonged sexual maturity, decreased offspring production and decreased swimming activity were observed for the F3 generation. In particular, it is difficult for D. magna to return to its normal level through a single-generation recovery in clean water in terms of reproductive function, ecological behavior and population health. Hence, multi-generational exposure to low concentrations of BPS can have adverse effects on population health of aquatic organisms with short breeding cycles, highlighting the necessity to assess the ecotoxicology of chronic BPS exposure for public health.

Occurrence, source apportionment and ecological risk assessment of thirty antibiotics in farmland system.

Antibiotics are widely used in medical care, livestock production, and aquaculture. However, antibiotic pollution has attracted increasing global concerns due to their ecological risks after entering into environmental ecosystem via animal excretion, effulent from industrial and domestic sewage treatment facilities. In this study, 30 antibiotics were investigated in soils and irrigation rivers using ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometer. This study evaluated the occurrence, source apportionment, and ecological risks of these target compounds in soils and irrigation rivers (i.e., sediments and water) of farmland system by using principal component analysis-multivariate linear regression (PCA-MLR) and risk quotients (RQ). The concentration range of antibiotics in soils, sediments, and water was 0.38-689.58 ng/g, 81.99-658.00 ng/g, and 134.45-1547.06 ng/L, respectively. In soils, the most abundant antibiotics were quinolones and antifungals with an average concentration of 30.00 ng/g and 7.69 ng/g, respectively, contributing to 40% of total antibiotics. Macrolides were the most frequently detected antibiotics in soils with an average concentration of 4.94 ng/g. In irrigation rivers, quinolones and tetracyclines, the most abundant antibiotics, accounted for 78% and 65% of antibiotics in water and sediments, respectively. Higher antibiotic contamination of irrigation water was primarily distributed in highly populated urban areas, while increasing antibiotic contamination of sediments and soils was particularly observed in rural areas. PCA-MLR analysis indicated that antibiotic contamination in soils was mainly ascribed to the irrigation of sewage-receiving water body and manure application of livestock and poultry farming, which cumulatively contributed to 76% of antibiotics. According to RQ assessment, quinolones in irrigation rivers posed high risk to algae and daphnia, contributing 85% and 72% to the mixture risk, respectively. In soils, macrolides, quinolones and sulfonamides were responsible for more than 90% to the mixture risk of antibiotics. Ultimately, these findings can improve our fundamental knowledge on contamination characteristics and source pathways towards risk management of antibiotics in farmland system.

Codon-optimized FAM132b gene therapy prevents dietary obesity by blockading adrenergic response and insulin action.

BACKGROUND: FAM132b (myonectin) has been identified as a muscle-derived myokine with exercise and has hormone activity in circulation to regulate iron homeostasis and lipid metabolism via unknown receptors. Here, we aim to explore the potential of adeno-associated virus to deliver FAM132b in vivo to develop a gene therapy against obesity. METHODS: Adeno-associated virus AAV9 were engineered to induce overexpression of FAM132b with two mutations, A136T and P159A. Then, AAV9 was delivered into high-fat diet mice through tail vein, and glucose homeostasis and obesity development of mice were observed. Methods of structural biology were used to predict the action site or receptor of the FAM132b mutant. RESULTS: Treatment of high-fat diet-fed mice with AAV9 improved glucose intolerance and insulin resistance, and resulted in reductions in body weight, fat depot, and adipocyte size. Codon-optimized FAM132b (coFAM132b) reduced the glycemic response to epinephrine (EPI) in the whole body and increased the lipolytic response to EPI in adipose tissues. However, FAM132b knockdown by shRNA significantly increased the glycemic response to EPI in vivo and reduced adipocyte response to EPI and adipose tissue browning. Structural analysis predicted that the FAM132b mutant with A136T and P159A may form a weak bond with ß2 adrenergic receptor (ADRB2) and may have more affinity for insulin and insulin-receptor complexes. CONCLUSIONS: Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating the adrenergic response and insulin action. Both structural biological analysis and in vivo experiments suggest that the adrenergic response and insulin action are most likely blockaded by FAM132b mutants.

Palladium-Catalyzed Difunctionalization of Alkenes by Relay Coupling with Propargylic Pyridines: Synthesis of Indolizine and Indolizinone-Containing Bisheterocycles.

Palladium-catalyzed arylation/heteroarylation of aryl halide-tethered alkenes with propargylic pyridines has been established, which provides direct and efficient access to various oxindole, azaoxindole, dihydrobenzopyran, indole, and benzofuran-linked indolizines in good yields with a broad substrate scope and high functional group tolerance. This process enables the formation of one C-N and two C-C bonds in a single operation through an intramolecular carbopalladation and cycloisomerization sequence. Furthermore, an indolizinone-linked bisheterocyclic framework containing indole and benzofuran could be synthesized conveniently from tertiary propargylic alcohols involving methyl or phenyl migration.

Effects of Nanoplastics and Butyl Methoxydibenzoylmethane on Early Zebrafish Embryos Identified by Single-Cell RNA Sequencing.

Nanoplastics with small particle sizes and high surface area/volume ratios easily absorb environmental pollutants and affect their bioavailability. In this study, polystyrene nanoplastic beads (PS-NPBs) with a particle size of 100 nm and butyl methoxydibenzoylmethane (BMDBM) sunscreen in personal-care products were chosen as target pollutants to study their developmental toxicity and interactive effects on zebrafish embryos. The exposure period was set from 2 to 12 h postfertilization (hpf). BMDBM and PS-NPBs significantly upregulated genes related to antioxidant enzymes and downregulated the gene expression of aromatase and DNA methyltransferases, but the influenced genes were not exactly the same. The combined exposure reduced the adverse effects on the expression of all genes. With the help of the single-cell RNA sequencing technology, neural mid cells were identified as the target cells of both pollutants, and brain development, head development, and the notch signaling pathway were the functions they commonly altered. The key genes and functions that are specifically affected by BMDBM and/or PS-NPBs were identified. BMDBM mainly affects the differentiation and fate of neurons in the central nervous system through the regulation of her5, her6, her11, lfng, pax2a, and fgfr4. The PS-NPBs regulate the expression of olig2, foxg1a, fzd8b, six3a, rx1, lhx2b, nkx2.1a, and sfrp5 to alter nervous system development, retinal development, and stem cell differentiation. The phenotypic responses of zebrafish larvae at 120 hpf were tested, and significant inhibition of locomotor activity was found, indicating that early effects on the central nervous system would have a sustained impact on the behavior of zebrafish.

A novel risk score for in-hospital perioperative mortality of five major surgeries.

BACKGROUND: Risk-scoring tools for perioperative mortality adjustment are essential for inter-hospital quality comparisons, which are still lacking in China. Existing scores had significant disadvantages when applied in managerial practice. OBJECTIVE: This study aimed to develop a simple risk score using highly accessible information that could appropriately adjust the perioperative mortality from major surgeries across tertiary Chinese public hospitals and provide a reference for other underdeveloped countries with the same need. METHODS: A study cohort from 19 hospitals was randomly split into a development set and an internal validation set in the ratio of 7:3. Another cohort from six hospitals was used as an external validation set. All data were obtained from the military-hospital public services database of the National Engineering Laboratory of Application Technology in Medical Big Data. Patients aged above 18 years undergoing one of the five categories of major surgical procedures between 1 January 2010 and 31 December 2020 were identified. The multivariate logistic regression analysis was used to predict the risk of mortality and derive the risk score. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess the discrimination and calibration of the model, respectively. RESULTS: The study set included 45 558 cases, divided into a development set containing 31 891 cases and an internal validation set with 13 667 cases. Another cohort with 14 956 cases was used as an external validation set. The final included predictor variables were age, Elixhauser Comorbidity Index, condition at admission, admission route and the procedure. The predicted risk score ranged from -21.5 to 37.0 points. The model discriminated well in the development set, internal validation set, and external validation set. The AUC for them were 0.753 (Standard Error(SE) 0.016, 95% Confidence Interval(CI): 0.721,0.784), 0.790 (SE 0.025, 95% CI: 0.742,0.839), and 0.766(SE 0.019, 95% CI: 0.728, 0.804), respectively. P values in the Hosmer-Lemeshow goodness-of-fit test were all above 0.05, indicating a good calibration. CONCLUSIONS: This risk-scoring model was proved to have satisfactory performance, allowing the rapid and effective risk adjustment of perioperative mortality when comparing the surgical quality in tertiary hospitals in China and other underdeveloped regions.

Occurrence, toxicity and ecological risk of Bisphenol A analogues in aquatic environment - A review.

Bisphenol analogues (BPs) have been widely applied to industry as the substitutes for bisphenol A (BPA), which have been detected frequently in surface water, sediment, sewage and sludge. The presence of BPs in natural environment could pose risks to the aquatic ecosystem and human health. This study outlined the occurrence, toxicity of BPs in aquatic environment and manifested their potential ecological risk to the aquatic ecosystem throughout the world. As for occurrence, BPA was losing its dominance, while BPs were occupying a large part, especially for bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). In some heavily polluted areas, BPs concentration reached µg/L in aquatic environment, which in the effluent of sewage plants was higher than that in the surface water. BPs content in sludge and sediment was more than that in the aqueous phase. All BPs other than BPS and Bisphenol P (BPP) had moderate toxicity. The current data supports that exposure to BPs may have adverse effects on dysfunction of endocrine system such as thyroid hormone concentration, enzyme activity, and even cell dysfunction, gene damage and chromosomal abnormalities. According to the risk quotient (RQ), BPF shows the highest ecological risk in China, Japan and South Korea, followed by BPA and BPS. The occurrence of bisphenols and their neurotoxicity on aquatic organisms merit further investigation.

Biodegradation of 2-ethylhexyl-4-methoxycinnamate in river sediments and its impact on microbial communities.

Numerous studies have evaluated the toxicity and endocrine disrupting properties of organic UV filters for aquatic organisms, but little is known about their biodegradation in river sediments and their impact on microorganisms. We have set up the sterile and microbiological systems in the laboratory, adding 2-ethylhexyl-4-methoxycinnamate (EHMC), one of organic UV filters included in the list of high yield chemicals, at concentrations of 2, 20 and 200 µg/L, and characterized the microbial community composition and diversity in sediments. Monitoring of EHMC degradation within 30 days revealed that the half-life in the microbial system (3.49 days) was much shorter than that in the sterile system (7.55 days). Two potential degradation products, 4-mercaptobenzoic acid and 3-methoxyphenol were identified in the microbial system. Furthermore, high-throughput 16s and 18s rRNA gene sequencing showed that Proteobacteria dominated the sediment bacterial assemblages followed by Chloroflexi, Acidobacteria, Bacteroidetes and Nitrospirae; Eukaryota_uncultured fungus dominated the sediment fungal assemblages. Correlation analysis demonstrated that two bacterium genera (Anaerolineaceae_uncultured and Burkholderiaceae_uncultured) were significantly correlated with the biodegradation of EHMC. These results illustrate the biodegradability of EHMC in river sediments and its potential impact on microbial communities, which can provide useful information for eliminating the pollution of organic UV filters in natural river systems and assessing their potential ecological risks.

Reagent-Controlled Divergent Synthesis of C-Glycosides.

By turning on or switching off the directing effect of the C3-OH-located o-diphenylphosphanylbenzoyl (o-DPPB) group in glycals, a reagent-controlled protocol for divergent and regio- and stereoselective syntheses of C-glycosides has been established. In particular, the silence of the directing effect of o-DPPB was achieved by the introduction of a ZnCl2 additive, which is operationally simple and efficient. The flexibility of the novel protocol was exhibited not only by the easy access of both α- and ß-C-glycosides but also by the versatility of the obtained formal Ferrier rearrangement products, which can be easily derivatized to various C-glycoside analogues owing to the embedded multifunctionalities.

Palladium-catalyzed C-glycosylation and annulation of o-alkynylanilines with 1-iodoglycals: convenient access to 3-indolyl-C-glycosides.

An efficient and practical approach for the synthesis of 3-indolyl-C-Δ1,2-glycosides through a palladium-catalyzed annulation/C-glycosylation sequence of o-alkynylanilines with 1-iodoglycals has been developed. This methodology has a wide scope of substrates and gives access to 3-indolyl-C-Δ1,2-glycosides in high yields. Furthermore, the product obtained here exhibits a high utility for further transformations.

Influence of aquatic colloids on the bioaccumulation and biological effects of diclofenac in zebrafish (Danio rerio).

Natural aquatic colloids play an important role in the migration, transformation of pollutants in the environment, but their potential effects are often ignored in ecotoxicology research. In this study, diclofenac (DCF) was selected as a typical drug to study the effects of natural colloids on the bioaccumulation and biotoxicity in juvenile zebrafish (Danio rerio) exposed to an environmentally relevant concentration (1 µg/L) and a high concentration (100 µg/L) of DCF. The results showed that the presence of colloids accelerated and enhanced the accumulation of DCF in zebrafish muscle and viscera, and the effects are greater at the environmentally relevant concentration of DCF. However, the colloids enhanced the burden in the head in the environmentally relevant concentration group, but reduced it in the high concentration group. This observation may be related to the occurrence of variations in the contribution of the adsorption forms of DCF and the colloids depending on different DCF concentrations. At the same time, the presence of colloids can significantly induce AChE activity of DCF in the brain and alter swimming activity and shoaling behaviour of the individuals, however no significant effects on the attack and shock behaviour were observed. These findings indicate that the combination of natural colloids and pollutants may change with pollutant concentrations, thereby altering the bioaccumulation and biological effects in aquatic organisms.

Biological uptake, depuration and biochemical effects of diclofenac and carbamazepine in Carassius carassius.

The uptake and depuration kinetics of diclofenac and carbamazepine alone at an environmentally relevant nominal concentration of 2 µg/L and in combination at a concentration ratio of 1:1 with total concentration of 4 µg/L were evaluated in Carassius carassius after 7 d uptake and depuration. Also, the biochemical effects of both drugs alone at nominal concentrations of 2 and 10 µg/L as well as in combination with total concentrations of 4 and 20 µg/L were investigated in Carassius carassius after 7 d exposure followed by 10 d recovery. In the single treatments, steady-state BCFs measured after the 7 d exposure were 73.05, 49.71, 38.01 and 24.93 L/kg for diclofenac and 9.25, 8.99, 5.29 and 4.11 L/kg for carbamazepine in the liver, brain, gill and muscle of Carassius carassius, respectively. Comparatively lower BCFs were measured in the tissues of Carassius carassius for both drugs in the combined treatments. Acetylcholinesterase activity in the brain was significantly induced by diclofenac while carbamazepine and the mixtures significantly inhibited it during all the exposure days as well as after the 10 d recovery in all treatments. This indicates that Carassius carassius could not recover from the neurotoxic effects caused by carbamazepine unlike the inductive effect caused by diclofenac which was recoverable after 10 days. A significant increase in the activities of 7-ethoxyresorufin O-deethylase and glutathione s-transferase for individual and mixed pharmaceuticals suggest that metabolism and detoxification of both drugs took place in the liver of Carassius carassius. Also, a significant increase in the activities of superoxide dismutase, catalase, glutathione reductase and malondialdehyde contents in the individual and mixture treatments mean that the antioxidant defence system of Carassius carassius was triggered to fight against oxidative stress but lipid peroxidation still occurred. However, Carassius carassius recovered from all these increases (superoxide dismutase, catalase, glutathione reductase and malondialdehyde) after the 10 d recovery, suggesting that oxidative damage is reversible. Our results indicate that both drugs at environmentally relevant concentrations might cause adverse effects in Carassius carassius and other fish species.

Ecological impact assessment of 110 micropollutants in the Yarlung Tsangpo River on the Tibetan Plateau.

In this study, the occurrences of 110 micropollutants in the surface waters and sediments collected at eight sampling sites along the middle reaches of the Yarlung Tsangpo River were investigated in winter. A total of 47 and 45 micropollutants were detected in at least one water or sediment sample, respectively, and their total concentrations reached 790.2 ng/L and 186.5 ng/g on a dry weight basis, respectively. Their composition profiles demonstrated that the majority of micropollutants were polycyclic aromatic hydrocarbons (PAHs) and UV filters. The mixture risk quotient (MRQ) values of the detected micropollutants regularly exceeded 1 for aquatic organisms at all sampling sites, and fish and invertebrates are the more sensitive organisms. The diversity and evenness of the zooplankton levels had a clear negative correlation with the micropollutant occurrences in water. The top 10 mixture components belonging to the UV filter and PAH categories explained more than 80% and 95% of the mixture risk for chronic and acute toxicology, respectively. This study is the first investigation of the presence and risk assessment of 110 micropollutants in the Yarlung Tsangpo River Basin and offers new insights into the ecological security of the water resources of the Tibetan Plateau.

The distribution pattern of endopolyploidy in maize.

KEY MESSAGE: We discovered that endopolyploidization is common in various organs and tissues of maize at different development stages. Endopolyploidy is not specific in maize germplasm populations. Endopolyploidy is caused by DNA endoreplication, a special type of mitosis with normal DNA synthesis and a lack of cell division; it is a common phenomenon and plays an important role in plant development. To systematically study the distribution pattern of endopolyploidy in maize, flow cytometry was used to determine the ploidy by measuring the cycle (C) value in various organs at different developmental stages, in embryos and endosperm during grain development, in roots under stress conditions, and in the roots of 119 inbred lines from two heterotic groups, Shaan A and Shaan B. Endopolyploidy was observed in most organs at various developmental stages except in expanded leaves and filaments. The endosperm showed the highest C value among all organs. During tissue development, the ploidy increased in all organs except the leaves. In addition, the endopolyploidization of the roots was significantly affected by drought stress. Multiple comparisons of the C values of seven subgroups revealed that the distribution of endopolyploidization was not correlated with the population structure. A correlation analysis at the seedling stage showed a positive relationship between the C value and both the length of the whole plant and the length of main root. A genome-wide association study (GWAS) identified a total of 9 significant SNPs associated with endopolyploidy (C value) in maize, and 8 candidate genes that participate in cell cycle regulation and DNA replication were uncovered in 119 maize inbred lines.