Synthesis, antibacterial activity, and 3D-QASR studies of matrine-indole derivatives as potential antibiotics.

Matrine and indole have antibacterial, anticancer, and other biological activities, in order to develop new antibiotics to solve the problem of multi-drug resistant bacteria. In this paper, we synthesized a series of 29 novel matrine derivatives as potential drug candidates by combining indole analogs and matrine. The antibacterial activity of these compounds was evaluated through minimum inhibitory concentration (MIC) assays against five bacterial strains (S. aureus, C. albicans, P. acnes, P. aeruginosa, and E. coli). The obtained results demonstrated promising antibacterial efficacy, particularly for compounds A20 and A18, which exhibited MICs.au values of 0.021 and 0.031 mg/ml, respectively, against S. aureus. Moreover, compounds A20 and A27 displayed remarkable MICc.al values of 2.806 and 4.519 mg/ml, respectively, against C. albicans, surpassing the performance of the clinical antibiotic penicillin G sodium (0.0368 mg/ml) and fluconazole (4.849 mg/ml). These findings underscore the significant bacteriostatic activity of the matrine derivatives. Furthermore, to gain a deeper understanding 3D-QSAR modeling was employed, revealing the critical influence of steric structure, charge distribution, hydrophobic interactions, and hydrogen bonding within the molecular structure on the bacteriostatic activity of the compounds. Additionally, molecular docking simulations shed light on the interaction between compound A20 and bacterial proteins, highlighting the involvement of hydrogen bonding, hydrophobic interactions, and π-π conjugation in the formation of stable complexes that inhibit the normal functioning of the proteins. This comprehensive analysis provided valuable insights into the antibacterial mechanism of the novel matrine derivatives, offering theoretical support for their potential application as antibiotics.

Trajectory of worst pain within the first two weeks following pelvic and sacral tumor surgery and long-term outcome: a pilot observational prospective cohort study.

BACKGROUND: Pain management after pelvic and sacral tumor surgery is challenging and requires a multidisciplinary and multimodal approach. Few data on postoperative pain trajectories have been reported after pelvic and sacral tumor surgery. The aim of this pilot study was to determine pain trajectories within the first 2 weeks after surgery and explore the impact on long-term pain outcomes. METHODS: Patients scheduled for pelvic and sacral tumor surgery were prospectively recruited. Worst/average pain scores were evaluated postoperatively using questions adapted from the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) until pain resolution was reached or up to 6 months after surgery. Pain trajectories over the first 2 weeks were compared using the k-means clustering algorithm. Whether pain trajectories were associated with long-term pain resolution and opioid cessation was assessed using Cox regression analysis. RESULTS: A total of 59 patients were included. Two distinct groups of trajectories for worst and average pain scores over the first 2 weeks were generated. The median pain duration in the high vs low pain group was 120.0 (95% CI [25.0, 215.0]) days vs 60.0 (95% CI [38.6, 81.4]) days (log rank p = 0.037). The median time to opioid cessation in the high vs low pain group was 60.0 (95% CI [30.0, 90.0]) days vs 7.0 (95% CI [4.7, 9.3]) days (log rank p < 0.001). After adjusting for patient and surgical factors, the high pain group was independently associated with prolonged opioid cessation (hazard ratio [HR] 2.423, 95% CI [1.254, 4.681], p = 0.008) but not pain resolution (HR 1.557, 95% CI [0.748, 3.243], p = 0.237). CONCLUSIONS: Postoperative pain is a significant problem among patients undergoing pelvic and sacral tumor surgery. High pain trajectories during the first 2 weeks after surgery were associated with delayed opioid cessation. Research is needed to explore interventions targeting pain trajectories and long-term pain outcomes. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov ( NCT03926858 , 25/04/2019).

Postoperative recovery after breast cancer surgery: A randomised controlled trial of opioid-based versus opioid-free anaesthesia with thoracic paravertebral block.

BACKGROUND: Perioperative use of opioids has revealed significant adverse effects associated with poor postoperative outcomes. OBJECTIVE: To determine whether opioid-free anaesthesia based on thoracic paravertebral block (TPVB) could improve postoperative recovery after breast cancer surgery. DESIGN: A randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Eighty adult women undergoing breast cancer surgery were enrolled. Key exclusion criteria included remote metastasis (but not to axillary lymph nodes of the surgical side), contraindication to interventions or drugs and a history of chronic pain or chronic opioid use. INTERVENTIONS: Eligible patients were randomised at a 1 : 1 ratio to receive either TPVB-based opioid-free anaesthesia (OFA group) or opioid-based anaesthesia (control group). MAIN OUTCOME MEASURES: The primary outcome was the global score of the 15-item Quality of Recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included postoperative pain and health-related quality of life. RESULTS: The QoR-15 global score was 140.3 ±â€Š5.2 in the OFA group and 132.0 ±â€Š12.0 in the control group ( P  < 0.001). The percentage of patients with good recovery (QoR-15 global score ≥118) was 100% (40/40) in the OFA group and 82.5% (33/40) in the control group ( P  = 0.012). Improved QoR in the OFA group was also evident in sensitivity analysis that rated QoR as excellent for a score of 136 to 150, as good at 122 to 135, as moderate at 90 to 121 and as poor at 0 to 89. The OFA group had higher scores in the domains of physical comfort (45.7 ±â€Š3.0 versus 41.8 ±â€Š5.7, P  < 0.001) and physical independence (18.3 ±â€Š2.2 versus 16.3 ±â€Š4.5, P  = 0.014). The two groups did not differ in pain outcomes or health-related quality of life. CONCLUSION: TPVB-based opioid-free anaesthesia improved early postoperative quality of recovery without compromising pain control in patients undergoing breast cancer surgery. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier: NCT04390698.

Tralomethrin causes cardiovascular toxicity in zebrafish (Danio rerio) embryos.

Tralomethrin, a synthetic pyrethroid insecticide used to control a wide range of pests in agriculture and public health, is highly toxic to aquatic organisms. However, data regarding the toxicity and underlying mechanisms of tralomethrin in aquatic organisms are limited. Thus, this study aimed to investigate the toxicity of tralomethrin in zebrafish. Zebrafish embryos were exposed to tralomethrin at different concentrations (16.63, 33.25, and 49.88 µg/L). Results showed that tralomethrin exposure caused cardiovascular dysplasia and dysfunction, including developmental abnormalities (pericardial edema, delayed yolk absorption, and uninflated swim bladder), elevated heart rate, and erythrogenesis disorders. Moreover, the expression patterns of crucial genes responsible for cardiovascular development (alas2, gata1a, hbbe2, nkx2.5, myl7, and myh6) also exhibited dysregulation in response to tralomethrin exposure. Oxidative stress occurred in embryos after exposure to tralomethrin. Collectively, our data suggest that exposure to tralomethrin induces cardiovascular and developmental toxicity in zebrafish. These findings are instrumental for evaluations of the environmental risk of tralomethrin in aquatic ecosystems in the future.

Distribution characteristics of microplastics in the soil of mangrove restoration wetland and the effects of microplastics on soil characteristics.

The dense vegetation in the wetland could effectively retain microplastic particles, and the distribution of microplastics varied significantly under different planting densities. In addition, microplastics in the soil environment can affect soil properties to a certain extent, which in turn can affect soil functions and biodiversity. In this study, we investigated the distribution of soil microplastics in a mangrove restoration wetland under different planting densities and their effects on wetland soil properties. The results indicated that the average abundance of soil microplastics was 2177.5 n/500 g, of which 70.9% exhibited a diameter ranging from 0.038-0.05 mm, while the remaining soil microplastics accounted for less than 20% of all microplastics, indicating that smaller-diameter microplastics were more likely to accumulate in wetland soil. The microplastic abundance could be ranked based on the planting density as follows: 0.5 × 0.5 m > 1.0 × 0.5 m > 1.0 × 1.0 m > control area. Raman spectroscopy revealed that the predominant microplastic categories in this region included polyethylene terephthalate (PET, 52%), polyethylene (PE, 24%) and polypropylene (PP, 15%). Scanning electron microscopy (SEM) images revealed fractures and tears on the surface of microplastics. EDS energy spectra indicated a large amount of metal elements on the surface of microplastics. Due to the adsorptive features of PET, this substance could influence the soil particle size distribution and thus the soil structure. All physicochemical factors, except for the soil pH, were significantly affected by PET. In addition, the CV analysis results indicated that soils in vegetated areas are more susceptible to PET than are soils in bare ground areas, leading to greater variation in their properties.

Bixafen exposure induces developmental toxicity in zebrafish (Danio rerio) embryos.

Bixafen (BIX), a new generation succinate dehydrogenase inhibitor (SDHI) fungicide commonly used in agriculture, is regarded as a potential aquatic pollutant because of its lethal and teratogenic effects on Xenopus tropicalis embryos. To evaluate the threat of BIX to aquatic environments, information concerning BIX's embryonic toxicity to aquatic organisms (especially fish) is important, yet such information remains scarce. The present study aimed to fill this knowledge gap by employing zebrafish embryos as model animals in exposure to 0.1, 0.3 and 0.9 µM BIX. Our results showed that BIX caused severe developmental abnormalities (hypopigmentation, tail deformity, spinal curvature and yolk sac absorption anomaly) and hatching delay in zebrafish embryos. The expression levels of early embryogenesis-related genes (gh, crx, sox2 and neuroD) were downregulated after BIX exposure, except for nkx2.4b, which was upregulated. Furthermore, transcriptome sequencing analysis showed that all the downregulated differentially expressed genes were enriched in cell cycle processes. Taken together, these results demonstrated that BIX has strong developmental toxicity to zebrafish that may be due to the downregulated expression of genes involved in embryonic development. These findings provide valuable reference for evaluating BIX's potential adverse effects on aquatic ecosystems.

Antioxidant, Hypolipidemic and Hepatic Protective Activities of Polysaccharides from Phascolosoma esculenta.

The aims of this study were to investigate the antioxidant, hypolipidemic and hepatic protective effects of Phascolosoma esculenta polysaccharides (PEP). PEP was prepared from Phascolosoma esculenta by enzyme hydrolysis and its characterization was analyzed. The antioxidant activities of PEP were evaluated by the assays of scavenging 1,1-Diphenyl-2-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radicals and chelating ferrous ion in vitro. It showed that PEP could scavenge radicals effectively and had favorable antioxidant activities. In the meantime, the hypolipidemic effect of PEP was investigated in vivo by using mice model fed with high-fat diet with or without PEP treatment. Compared with the hyperlipidemic mice without treatment, the serum levels of total cholesterol (TC) (30.1-35.7%, p < 0.01), triglyceride (TG) (24.5-50.8%, p < 0.01 or p < 0.05), low-density lipoprotein cholesterol (LDL-C) (49.6-56.8%, p < 0.01) and liver levels of TC (21.0-28.4%, p < 0.01), TG (23.8-37.0%, p < 0.01) decreased significantly, whereas serum high-density lipoprotein cholesterol (HDL-C) (47.7-59.9%, p < 0.01 or p < 0.05) increased significantly after treatment with different dosage of PEP (0.2, 0.4 and 0.8 g per kg body weight, respectively). In addition, superoxide dismutase (SOD) (10.2-22.2% and 18.8-26.9%, p < 0.05), glutathione peroxidase (GSH-Px) (11.9-15.4% and 26.6-30.4%, p < 0.05) activities in serum and liver enhanced markedly while aspartate aminotransferase (AST) (18.7-29.6% and 42.4-58.0%, p < 0.05), alanine transaminase (ALT) (42.7-46.0% and 31.2-42.2%, p < 0.05) activities, as well as the levels of malondialdehyde (MDA) (15.9-24.4% and 15.0-16.8%, p < 0.01 or p < 0.05) in serum and liver reduced markedly. Moreover, the histopathological observation of livers indicated that PEP could attenuate liver cell injury. The animal experimental results demonstrated that PEP exerted hypolipidemic and hepatoprotective roles in hyperlipidemic mice. In summary, our results above suggest that PEP might be a potential natural antioxidant and utilized as a therapeutic candidate for hyperlipidemia.

[Research advances on hypolipidemic effect of polysaccharides].

Hyperlipidemia is a systemic chronic metabolic disease caused by dyslipidemia in the body. It is an important risk factor of accelerating atherosclerosis, which will cause coronary heart disease, thrombus and other cardiovascular diseases, so it is a "invisible killer" for human health. Controlling and lowering blood lipids can reduce the risk of cardiovascular and cerebrovascular diseases. The current therapies for hyperlipidemia mainly include chemical synthetic medicines. However, long-term use of hypolipidemic drugs would cause various side effects, and the demand of effective and nontoxic drugs for hyperlipidemia patients is eager. Polysaccharide has attracted worldwide concerns due to its characteristics of good biocompatibility and less side effects. Polysaccharide is a kind of biological macromolecule which is widely found in plant cell walls, animal cell membranes and microorganism cell walls. A number of studies have shown that polysaccharides from natural materials have broad biological activities, such as anti-tumor, immunomodulatory, antioxidant, hypoglycemic, and hypolipidemic effects, with broad application prospect. This paper has reviewed and summarized the polysaccharides with hypolipidemic effect and their mechanisms which have been reported at home and abroad, hoping to provide certain reference for their development and application in lowering blood lipids.

Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

Preparation, antibacterial activity, and structure-activity relationship of low molecular weight κ-carrageenan.

κ-Carrageenan (KC) is a polysaccharide widely used in food industry. It has been widely studied for its excellent physicochemical and beneficial properties. However, the high molecular weight and high viscosity of KC make it difficult to be absorbed and to exert its' biological activities, thus limit its extensive industrial application. In order to solve this problem, five low molecular weight κ-carrageenans (DCPs) were prepared by the degradation of KC using hydrogen peroxide (H2O2) and ascorbic acid (AH2). The chemical compositions and structure characteristics of the DCPs were then determined. The results showed that H2O2 and AH2 could effectively degrade KC to DCPs, and DCPs remained the basic skeletal structure of KC. DCPs showed good antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The Minimum Inhibitory Concentration (MIC) of DCPs with the highest antibacterial effects were 5.25, 4.5, 5.25, and 4.5 mg/mL, respectively. This is due to the underlying mechanism of DCPs that bind to the bacterial membrane proteins and change the membrane permeability, thus exerting antibacterial activity. In addition, Spearman's rank correlation and Ridge regression analysis revealed that the molecular weight and the contents of 3,6-anhydro-D-galactose, aldehyde group, carboxyl, and sulfate were the main structural characteristics affecting the antibacterial activity. Our findings reveal that the H2O2-AH2 degradation treatment could significantly improve the antibacterial activity of KC and provide insights into the quantitative structure-activity relationships of the antibacterial activity of DCPs.

Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

Diafenthiuron causes developmental toxicity in zebrafish (Danio rerio).

Diafenthiuron, a broad-spectrum insecticide and acaricide used for agricultural crop protection, is highly toxic to nontarget organisms. However, the developmental toxicity of diafenthiuron and its underlying mechanisms are not fully understood. Thus, the purpose of this study was to investigate the developmental toxicity of diafenthiuron in zebrafish. Zebrafish embryos were exposed to diafenthiuron at different concentrations (0.01, 0.1, and 1 µM) from 3 to 120 h post fertilization (hpf). Diafenthiuron exposure significantly shortened the body lengths of zebrafish larvae and significantly decreased superoxide dismutase activity. It also downregulated the spatiotemporal expression of pomc and prl, marker genes involved in pituitary development. Moreover, diafenthiuron exposure downregulated the spatiotemporal expression of liver-specific marker, fabp10a, and inhibited the development of the liver, a detoxification organ. In conclusion, our data provide evidence of the developmental toxicity and hepatotoxicity of diafenthiuron in aquatic organisms, and they are instrumental for further environmental risk assessment of diafenthiuron in aquatic ecosystems.

Preoperative resting-state microstate as a marker for chronic pain after breast cancer surgery.

INTRODUCTION: Chronic postoperative pain poses challenges, emphasizing the importance of accurately predicting pain in advance. Generally, pain perception is associated with the temporal dynamics of the brain, which can be represented by microstates. Specifically, microstates are transient and patterned brain topographies formed by temporally overlapping and spatially synchronized oscillatory activities. Consequently, by characterizing brain activity, microstates offer valuable insights into pain perception. METHODS: In this prospective study, 66 female patients undergoing breast cancer surgery were included. Their preoperative resting-state electroencephalography (EEG) was recorded. Preoperative resting-state EEG was recorded and four specific brain microstates (labeled as A, B, C, and D) were extracted. Temporal characteristics were then analyzed from these microstates. Patients were classified into two groups based on their Numerical Rating Scale (NRS) scores at three months postoperatively. Those with NRS scores ranging from 4 to 10 were classified as the high pain group, while patients with NRS ranging from 0 to 3 were classified as the lowpain group. Statistical analyses were performed to compare the microstate characteristics between these two groups. RESULTS: Twenty-one patients (32%) were classified as the high pain group and forty-five (68%) as the low-pain group. The occurrence and coverage of microstate C were significantly higher in the high pain group. Additionally, there were significant differences in the microstates transitions between the two groups. Furthermore, the study revealed a positive correlation between the coverage of microstate C and the NRS. CONCLUSIONS: Preoperative resting-state microstate features have shown correlations with postoperative pain. This study presents a novel and advanced perspective on the potential of microstates as a marker for postoperative pain.

The joint detection of CEA and ctDNA in cerebrospinal fluid: an auxiliary tool for the diagnosis of leptomeningeal metastases in cancer.

BACKGROUND: Leptomeningeal metastases (LMs) are highly invasive which leads to poor prognosis, but the accurate diagnosis of LM is challenging. It is necessary to investigate more advanced diagnostic methods to realize precision medicine. The main purpose of this study was to select a more effective method for the auxiliary diagnosis of LM by comparing various detection methods. The secondary purpose was to explore the value of cerebrospinal fluid (CSF) tumor markers (TMs) and circulating tumor DNA (ctDNA) testing in guiding clinical treatment. METHODS: TMs in serum and CSF of patients were detected by chemiluminescence. The ctDNA of CSF and plasma were detected by the next-generation sequencing (NGS) technology. RESULTS: In total, 54 tumor patients participated in this study, in which 39 with LM and 15 without LM (8 with parenchymal tumor and 7 without brain metastasis). The results showed that the sensitivity and accuracy of CSF cytology isolated during the first lumbar puncture were 0.31 (95% CI 0.17-0.48) and 0.50 (95% CI 0.36-0.64), respectively. The sensitivity and accuracy of CSF_CEA were 0.71 (95% CI 0.54-0.85) and 0.78 (95% CI 0.64-0.89), which were better than those of CSF_NSE and CSF_CFRA-211. The sensitivity and accuracy of CSF_ctDNA were 0.92 (95% CI 0.79-0.98) and 0.91 (95% CI 0.80-0.97), significantly higher than that of CSF cytology (P < 0.01). The sensitivity and accuracy of CSF_CEA combined with CSF_ctDNA were 0.97 (95% CI, 0.87-1.00) and 0.94 (95% CI 0.85-0.99), which were significantly higher than the traditional methods CSF cytology (P < 0.01). For LM patients with hydrocephalus, the sensitivity of CSF ctDNA even achieved 100% (14/14). CONCLUSION: CSF_CEA combined with CSF_ctDNA could be used to accurately distinguish patients with LM from those with no brain metastasis and from those with parenchymal tumors. CSF_ctDNA testing reveals a unique mutation profile for patients with LM. Dynamic detection of CSF TM and ctDNA can better predict the efficacy and reveal the cause of drug resistance to guide subsequent treatment. CLINICAL TRIAL REGISTRATION: Clinical trial registration number: NCT03029065.

Inhibitory effect of polyethylene microplastics on roxarsone degradation in soils.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox(V)), an extensively used organoarsenical feed additive, enters soils through the application of Rox(V)-containing manure and further degrades to highly toxic arsenicals. Microplastics, as emerging contaminants, are also frequently detected in soils. However, the effects of microplastics on soil Rox(V) degradation are unknown. A microcosm experiment was conducted to investigate soil Rox(V) degradation responses to polyethylene (PE) microplastics and the underlying mechanisms. PE microplastics inhibited soil Rox(V) degradation, with the main products being 3-amino-4-hydroxyphenylarsonic acid [3-AHPAA(V)], N-acetyl-4-hydroxy-m-arsanilic acid [N-AHPAA(V)], arsenate [As(V)], and arsenite [As(III)]. This inhibition was likely driven by the decline in soil pH by PE microplastic addition, which may directly enhance Rox(V) sorption in soils. The decreased soil pH further suppressed the nfnB gene related to nitroreduction of Rox(V) to 3-AHPAA(V) and nhoA gene associated with acetylation of 3-AHPAA(V) to N-AHPAA(V), accompanied by a decrease in the relative abundance of possible Rox(V)-degrading bacteria (e.g., Pseudomonadales), although the diversity, composition, network complexity, and assembly of soil bacterial communities were largely influenced by Rox(V) rather than PE microplastics. Our study emphasizes microplastic-induced inhibition of Rox(V) degradation in soils and the need to consider the role of microplastics in better risk assessment and remediation of Rox(V)-contaminated soils.

Roxarsone biotransformation by a nitroreductase and an acetyltransferase in Pseudomonas chlororaphis, a bacterium isolated from soil.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox), a widely used organoarsenical feed additive, can enter soils and be further biotransformed into various arsenic species that pose human health and ecological risks. However, the pathway and molecular mechanism of Rox biotransformation by soil microbes are not well studied. Therefore, in this study, we isolated a Rox-transforming bacterium from manure-fertilized soil and identified it as Pseudomonas chlororaphis through morphological analysis and 16S rRNA gene sequencing. Pseudomonas chlororaphis was able to biotransform Rox to 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), N-acetyl-4-hydroxy-m-arsanilic acid (N-AHPAA), arsenate [As(V)], arsenite [As(III)], and dimethylarsenate [DMAs(V)]. The complete genome of Pseudomonas chlororaphis was sequenced. PcmdaB, encoding a nitroreductase, and PcnhoA, encoding an acetyltransferase, were identified in the genome of Pseudomonas chlororaphis. Expression of PcmdaB and PcnhoA in E. coli Rosetta was shown to confer Rox(III) and 3-AHPAA(III) resistance through Rox nitroreduction and 3-AHPAA acetylation, respectively. The PcMdaB and PcNhoA enzymes were further purified and functionally characterized in vitro. The kinetic data of both PcMdaB and PcNhoA were well fit to the Michaelis-Menten equation, and nitroreduction catalyzed by PcMdaB is the rate-limiting step for Rox transformation. Our results provide new insights into the environmental risk assessment and bioremediation of Rox(V)-contaminated soils.

Benfuracarb inhibits body growth and causes oxidative stress in zebrafish (Danio rerio).

Benfuracarb (BEN), a broad-spectrum carbamate insecticide used for crop protection, is considered toxic to humans and aquatic organisms. However, the potential risk level of BEN to aquatic organisms is still unclear. In this study, we exposed zebrafish embryos to BEN (0.08, 0.49, and 0.90 mg/L) from 3 to 96 hours post-fertilization (hpf). The results showed that BEN caused shorter body length in zebrafish larvae. The activity of superoxide dismutase (SOD) was significantly increased after BEN exposure. Furthermore, the transcription levels of marker genes associated with early embryonic development (myoD, nkx2.4b, myh6, and gh) were disrupted after BEN treatment. Taken together, the data indicate that BEN possesses developmental toxicity to zebrafish. The results provide a valuable reference for assessing BEN's potentially harmful effects on aquatic ecosystems.

A novel methodology to integrate outcomes regarding perioperative pain experience into a composite score: Prediction model development and validation.

BACKGROUND: An integrated score that globally assesses perioperative pain experience and rationally weights each component has not yet been developed. METHODS: A development dataset specific to adult Chinese patients undergoing orthopaedic surgery was obtained from PAIN OUT (1985 qualified patients of 2244). A more recent validation dataset obeying the same conditions was obtained from the Chinese Anaesthesia Shared-database Platform (1004 qualified patients of 1032). Outcomes were assessed using the International Pain Outcomes Questionnaire (IPO-Q), which comprises key patient-level outcomes of perioperative pain management, including pain experience and perceptions of care. Using principal component analysis and regression models, a composite score (CS) was inferred to integrate pain experience. The discrimination of the CS for dissatisfaction and desire for more pain treatment was compared with that of the worst pain score. RESULTS: A CS was developed from the 12 items of the IPO-Q regarding pain experience. The weight for calculating the CS was worst pain 11, least pain 17, time spent in severe pain 11, interference with activity in bed 9, interference with breathing deeply or coughing 10, interference with sleep 9, anxiety 12, helplessness 12, nausea 0, drowsiness 2, itch 5 and dizziness 2. In external validation, the CS indicated superior discrimination to the worst pain in predicting dissatisfaction (p < 0.001) and desire for more pain treatment (p < 0.001). CONCLUSIONS: This study introduced a methodology to integrate outcomes regarding perioperative pain experience into a CS, which was based on the weight of each item. SIGNIFICANCE: This novel methodology sheds additional light on the riveting issue of carefully integrating several measures into a composite endpoint, which may be useful for quality improvement purposes when addressing the impact of a change in clinical practice.

The influence of involving patients in postoperative pain treatment decisions on pain-related patient-reported outcomes: A STROBE-compliant registering observational study.

The evidence regarding the influence of allowing patients to participate in postoperative pain treatment decisions on acute pain management is contradictory. This study aimed to identify the role of patient participation in influencing pain-related patient-reported outcomes (PROs). This is a cross-sectional study. The data were provided by PAIN OUT (www.pain-out.eu). A dataset specific to adult Chinese patients undergoing orthopedic surgery was selected. The PROs were assessed on postoperative day 1. The patient participant was assessed using an 11-point scale. Participants who reported >5 were allocated to the "participation" group, and those who reported ≤5 were allocated to the "nonparticipation" group. A 1:1 propensity score matching was conducted. The primary outcome was the desire for more pain treatment. All other items of PROs were the secondary outcomes comprising pain intensity, interference of pain with function, emotional impairment, adverse effects, and other patient perception. From February 2014 to November 2020, 2244 patients from 20 centers were approached, of whom 1804 patients were eligible and 726 pairs were matched. There was no significant difference between the groups in the desire for more pain treatment either before (25.4% vs 28.2%, risk ratio [95% CI]: 0.90 [0.77, 1.05], P = .18) or after matching (26.7% vs 28.8%, risk ratio [95% CI]: 0.93 [0.79, 1.10], P = .43). After matching, patients in the participation group reported significantly better PROs, including pain intensity (less time spent in severe pain [P < .01]), emotional impairment (less anxiety [P < .01]), interference with function (less interference with sleep [P < .01]), adverse effects (less drowsiness [P = .01]), and patient perception (more pain relief [P < .01] and more satisfaction [P < .01]), than the nonparticipation group. Patient participation in pain treatment decisions was associated with improved pain experience but failed to mitigate the desire for more treatment.

Supplementation of cooked broccoli with exogenous moringa myrosinase enhanced isothiocyanate formation.

Brassica vegetables, especially broccoli, have health benefits such as anticancer activity, which are attributed to isothiocyanate (ITC), products of glucosinolate hydrolysis. This study aimed to explore the effect of cooking time and addition of exogenous myrosinase (MYR) from moringa seeds on the yield of ITCs. The results showed that raw broccoli produced a significantly high amount of ITCs, which decreased by almost 40% after microwaving the broccoli for 1 min. Introducing exogenous MYR by adding ground moringa seeds to cooked broccoli caused a notable increase in ITC of 38%. At pH 4.0-6.0, MYR showed optimal activity, and the thermal stability of MYR from moringa seeds was better than that from broccoli. The kinetic parameters indicated that MYR from moringa seeds had a higher affinity to sinigrin than that from broccoli seeds. This study was novel in reporting that adding ground moringa seeds to cooked broccoli enhanced ITC formation.