Pharmacokinetics of tilmicosin in plasma, urine and feces after a single intragastric administration in donkey (Equus asinus).

Tilmicosin, a macrolide antibiotic, has the potential to treat bacterial infections in donkeys. However, the pharmacokinetics of tilmicosin in donkeys have not been reported. The aim of this study was to investigate the pharmacokinetics of tilmicosin in donkey plasma, urine, and feces after a single intragastric administration to determine the suitability of tilmicosin for donkeys. A total of 5 healthy male donkeys with similar body weights were selected. The donkeys were administered a single dose of 10 mg · kg-1 body weight (BW) tilmicosin by gavage. The concentrations of tilmicosin in plasma, urine, and feces were determined. The results showed that after a single intragastric administration of 10 mg · kg-1 body weight, tilmicosin in donkey plasma reached a maximum concentration of 11.23 ± 5.37 mg · L-1 at 0.80 ± 0.10 h, with a half-life of 14.49 ± 7.13 h, a mean residence time of 28.05 ± 3.05 h, a Cl/F of 0.48 ± 0.18 L · kg-1 · h-1, and a Vd/F of 9.28 ± 2.63 Lkg-1. The percentage of tilmicosin excreted through the urine of donkeys is 2.47%, and the percentage excreted through the feces is 66.43%. Our study provides data to inform the use of tilmicosin in donkeys.

Combined cytotoxicity of phthalate esters on HepG2 cells: A comprehensive analysis of transcriptomics and metabolomics.

Phthalate esters (PAEs), widely used as plasticizers, may pose a potential environmental and human hazard. The aim of this study was to compare the cytotoxicity of di(2-ethylhexyl) phthalates (DEHP) and dibutyl phthalate (DBP)) after their exposure to HepG2 cells alone or in combination. HepG2 cells treated with individual/combined DEHP and DBP at a dose of 10-2 M for 24 h were selected for metabolome and transcriptome analysis. The results demonstrated that exposure to the mixtures of DEHP and DBP caused enhanced or reduced toxic effects regarding 8 pathways with 1065 downregulated genes and 643 upregulated genes, in comparison with those of single chemicals. The combined toxicity of mixture revealed both synergistic and antagonistic interactions between DEHP and DBP. Besides, combined exposure to DEHP and DBP promoted TCA cycle, pyrimidine, and purine metabolism, while an antagonistic effect on fatty acid derangement should require further investigation. To summarize, our results suggest that DEHP exposed alone or combined with DBP caused a variety of metabolic disorders, and the type of combination effects varied among metabolic pathways.

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in the plasma, urine, and feces of fattening male donkeys following single oral administration.

Florfenicol (FF) is a commonly used antibacterial agent in animals. We investigated the pharmacokinetics of FF and its metabolite florfenicol amine (FFA) in donkeys. Donkeys were administered FF (30 mg/kg bodyweight, p.o.). Pharmacokinetic parameters were calculated using a non-compartmental model. The FF (FFA) pharmacokinetics parameters were characterized by along elimination half-life (t1/2 kz) of 5.92 h (15.95 h), plasma peak concentration (Cmax) of 0.13 µg/mL (0.08 µg/mL), and the time taken to reach Cmax (Tmax) of 0.68 h (0.72 h). The area under plasma concentration-time curve and mean residence time of FF (FFA) in plasma were 1.31 µg·mL-1·h (0.47 µg·mL-1·h) and 10.37 h (18.40 h), respectively. The t1/2 kz of FF and FFA in urine was 21.93 and 40.26 h, and the maximum excretion rate was 10.56 and 4.03 µg/h reached at 25.60 and 32.20 h, respectively. The respective values in feces were 0.02 and 0.01 µg·h-1 reached at 33.40 h. The amount of FF and FFA recovered in feces was 0.52 and 0.22 µg, respectively. In conclusion, FF (FFA) is rapidly absorbed and slowly eliminated after a single oral administration to donkeys. Compared to FF, FFA was more slowly eliminated. FF (FFA) is mostly excreted through urine.

Dynamics of Acute Postsurgical Pain over the Last Decade: A Bibliometric Analysis.

Objective: Minimizing acute postsurgical pain (APSP) remains a challenge, despite extensive research about it. This study comprehensively analyzed the literature on APSP to assess how the field has developed and where it may go in the future. Methods: Studies on APSP indexed in the Web of Science Core Collection and published from 2012 to 2021 were assessed for eligibility. Data from included studies were analyzed using CiteSpace, Python, and Microsoft. Results: Analysis of 5,236 publications on APSP showed that the number of articles per year has increased linearly. The United States leads other countries in terms of the number and centrality of publications. Cocitation analysis suggests that the field focused earlier on the incidence and risk factors of APSP, shifting later to a focus on the reduction and management of adverse outcomes due to APSP. The top-ranked keyword cluster during the study period was "short-term outcomes" (#0), followed by "risk factors" (#1). The strongest burst occurred for the keyword "combination," followed by "multimodal analgesia." The most recent burst occurred for the keywords "regional analgesia," "opioid use," "erector spinae plane block," and "infiltration." Conclusions: Hotspots in APSP research since 2012 have been incidence, risk factors, and control of negative outcomes. Future research is likely to concentrate on the use of opioids and technological innovations in regional anesthesia. Our findings may help APSP researchers and clinicians understand their field, optimize clinical practice, and plan future research.

The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity.

As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.

Phonomyography on Perioperative Neuromuscular Monitoring: An Overview.

Complications related to neuromuscular blockade (NMB) could occur during anesthesia induction, maintenance, and emergency. It is recommended that neuromuscular monitoring techniques be utilized perioperatively to avoid adverse outcomes. However, current neuromuscular monitoring methods possess different shortcomings. They are cumbersome to use, susceptible to disturbances, and have limited alternative monitoring sites. Phonomyography (PMG) monitoring based on the acoustic signals yielded by skeletal muscle contraction is emerging as an interesting and innovative method. This technique is characterized by its convenience, stable signal quality, and multimuscle recording ability and shows great potential in the application field. This review summarizes the progression of PMG on perioperative neuromuscular monitoring chronologically and presents the merits, demerits, and challenges of PMG-based equipment, aiming at underscoring the potential of PMG-based apparatuses for neuromuscular monitoring.

Dysregulated circulating miR-4429 serves as a novel non-invasive biomarker and is correlated with EGFR mutation in patients with non-small cell lung cancer.

This study aimed to investigate the correlation between microRNA (miR)-4429 and epidermal growth factor receptor (EGFR), the expression and clinical significance of miR-4429 in patients with non-small cell lung cancer (NSCLC), and the relationship between miR-4429 and EGFR mutation in NSCLC patients. Blood samples were collected from 122 NSCLC patients and 72 healthy volunteers. miR-4429 expression and EGFR mRNA expression were detected by real-time quantitative PCR. Correlation between miR-4429 and EGFR was evaluated by dual­luciferase reporter assay and the Pearson correlation analysis. The ability of serum miR­4429 to discriminate between NSCLC patients and healthy controls, and to discriminate between EGFR wild-type (EGFR-W) and EGFR mutant-type (EGFR-M) patients was assessed using receiver operating characteristic analysis. The relationship between miR-4429 and NSCLC patients' survival was identified by Kaplan-Meier survival curves and log-rank test. The prognostic value of miR-4429 in NSCLC patients was evaluated by Cox regression analysis. miR-4429 could directly bind to EGFR. Serum miR-4429, decreased in NSCLC patients, was negatively correlated with serum EGFR mRNA expression in NSCLC patients. Additionally, miR-4429 had a high diagnostic value for screening NSCLC patients from healthy controls, and was independently correlated with survival prognosis of NSCLC patients. Moreover, miR­4429 was decreased in EGFR-M patients, which had a certain screening ability for EGFR­M patients. Our findings indicate that miR-4429 is negatively correlated with EGFR in NSCLC, and may function as a diagnostic and prognostic biomarker for NSCLC patients. Additionally, miR-4429 is associated with EGFR mutation in NSCLC patients.

Evaluation of canthaxanthin in eggs and its subsequent dietary risks to Chinese consumers.

Canthaxanthin is a colourant widely used in medicine, food and cosmetics, which is closely related to human eye dysfunction. The EU determines that the daily acceptable intake of canthaxanthin (ADI) is 0.03 mg canthaxanthin per kg body weight. In order to protect people's diet health and avoid the occurrence of food safety accidents, this paper measured the content of canthaxanthin in 114 egg samples sourced from different regions of China using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The dietary exposure assessment method was used to evaluate the dietary risk to Chinese consumers. Results showed that the content of canthaxanthin varies significantly across regions of origin, with eggs produced in Beijing having a lower amount than those from other regions. The average dietary exposure of children (2-10 years old) was 0.242 ~ 0.653 µg/(kg bw∙d), and the dietary exposure of 95/97.5/99 percentile was 0.246 ~ 1.779 µg/(kg bw∙d). The maximum exposure was 3.089 µg/(kg bw∙d), and its risk quotient was 0.103 (<1), which was an acceptable risk. For the teenager group (11-18 years old), the average dietary exposure was 0.141 ~ 0.247 µg/(kg bw∙d), and the dietary exposure at the 95/97.5/99 percentile was 0.143 ~ 0.671 µg/(kg bw∙d), presenting an acceptable risk. For adults, the dietary risk of eating eggs with canthaxanthin is the lowest among the three age groups.

Analysis of heavy metal content in edible honeysuckle (Lonicera japonica Thunb.) from China and health risk assessment.

Honeysuckle is a commonly used medicine for health care and treatment. To detect heavy metal pollution in honeysuckle from China and quantify the health risk of heavy metal via dietary intake, the Pb, Cd, Cr, As, Hg, Ni, Mn, Cu, and Zn contents in honeysuckle samples were determined by ICP-MS. The dissolution rate of heavy metals in honeysuckle was measured by decoction and soaking. The hazard quotient (HQ) and total hazard index (HI) were used to evaluate the noncarcinogenic risk of nine heavy metals in honeysuckle, and the carcinogenic risks of Cd and As were evaluated using the carcinogen risk. Cd exhibited the maximum permissive limit standard-exceeding rate (40.2%) in honeysuckle, followed by Cu (37.6%) and Pb (8.5%). As and Hg did not exceed the standard values, and Cr, Ni, Mn, and Zn had no limits. In a decoction fluid after 30 min of boiling, the transfer rates of Pb, Cd, As, Ni, Mn, Cu, and Zn ranged from 11.9% to 19.9%, whereas that of Cr was low (1.0%). In a soaking fluid, the transfer rates ranged from 17.0% to 56.9%; no transfer rate was detected for Hg in neither the decoction fluid nor the soaking fluid. In addition, the 95th percentile Rs of As and Cd in honeysuckle were 5.93 × 10-6 and 8.12 × 10-5, respectively. The carcinogenic risk of Cd at 56.99th percentile reached the threshold set by the World Health Organization (1.0 × 10-5). The results showed that intake of Pb, Cd, Cr, As, Hg, Ni, Mn, Cu, and Zn by the human body through honeysuckle could not cause noncarcinogenic damage. The element As had no carcinogenic risk, but Cd had a carcinogenic risk to a certain extent.

Determination of testosterone/epitestosterone concentration ratio in human urine by capillary electrophoresis.

A novel method for determining the testosterone/epitestosterone concentration ratio in human urine was established by capillary electrophoresis with diode-array detector. The urine samples were firstly purified by the solid extraction. The optimal experimental conditions were: running buffer pH = 4.74, 15.0 mmol L-1 HAc-NaAc, separation voltage 25 kV, temperature 25 °C, sample injection pressure 3.43 × 103 Pa, and duration 10 s. The testosterone and epitestosterone linear range were determined as 8.0-960.0 ng mL-1, respectively. The testosterone and epitestosterone detection limits were determined as 4.6 and 4.5 ng mL-1, respectively. The relative standard deviation was less than 0.36%.

Light- and temperature-assisted spin state annealing: accessing the hidden multistability.

Among responsive multistable materials, spin crossover (SCO) systems are of particular interest for stabilizing multiple spin states with various stimulus inputs and physical outputs. Here, in a 2D Hofmann-type coordination polymer, [Fe(isoq)2{Au(CN)2}2] (isoq = isoquinoline), a medium-temperature annealing process is introduced after light/temperature stimulation, which accesses the hidden multistability of the spin state. With the combined effort of magnetic, crystallographic and Mössbauer spectral investigation, these distinct spin states are identified and the light- and temperature-assisted transition pathways are clarified. Such excitation-relaxation and trapping-relaxation joint mechanisms, as ingenious interplays between the kinetic and thermodynamic effects, uncover hidden possibilities for the discovery of multistable materials and the development of multistate intelligent devices.

Fast determination of 14 mycotoxins in chestnut by dispersive solid-phase extraction coupled with ultra high performance liquid chromatography-tandem mass spectrometry.

A dispersive solid-phase extraction coupled with ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of T-2 toxin, penicillic acid, fumonisins B1 , B2 , and B3 , aflatoxins B1 , B2 , G1 , and G2 , ochratoxin A, deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and zearalenone in chestnut samples. The method was used to analyze 136 samples obtained from Shandong province in China. The mycotoxins were extracted using a dispersive solid-phase extraction method and cleaned using an improved quick, easy, cheap, effective, rugged, and safe approach. The mycotoxins were then detected using a triple-quadrupole mass spectrometer. The limits of detection and quantification ranged from 0.02 to 1 and 0.1 to 2 µg/kg, respectively. The recovery rates ranged from 74.2 to 109.5%, with relative standard deviations below 15%. A total of 71 samples were contaminated with seven mycotoxins at concentrations ranging from 1.2 to 105.5 µg/kg, with a number of samples exceeding the maximum limits set in the European regulations for mycotoxins in unprocessed chestnuts.

Mxene/alginate composites for lead and copper ion removal from aqueous solutions.

Mxene has been widely used as a sorbent to remove heavy metal ions from sewage due to its unique two-dimensional layered structure and abundant oxygen-containing groups. However, Mxene has a relatively limited adsorption capacity for metal ions possibly due to the limited adsorption active sites. Herein, we reported novel Mxene/alginate composites for lead and copper ion removal from wastewater. The Mxene/alginate composites prepared in this study not only enhance the chelation ability of the lead and copper ions, but also accelerate the ion transport efficiency. The combined advantages of high adsorption capacity and short equilibrium time enable the Mxene/alginate composites to achieve the maximum adsorption capacity for Pb2+ and Cu2+ at 382.7 and 87.6 mg g-1, respectively, and reach the adsorption equilibrium in 15 min. We believe that the composites developed in this study can open a new avenue for designing high adsorption capacity and high efficiency adsorbents.

Epidemic characteristics of main infectious diseases in Yantai city between 2010 and 2012 and prevention strategy research.

To investigate the epidemic characteristics and prevention strategies of main infectious diseases. From 2010 to 2012, 23 notifiable diseases were reported in Yantai with average reported cases of 17,376. The morbidity was the highest in 2012 and the lowest in 2011. The accumulated death toll was 101 with the highest death rate in 2011 and the lowest in 2012. Major class A and B infectious diseases included viral hepatitis, phthisis, syphilis, clap and dysentery. The major class C infectious disease was hand-foot-and-mouth disease every year. The distribution of transmission routes of HIV/AIDS among patients with HIV and AIDS in Yantai were investigated. The overall condition of phthisis in Yantai showed stable with slight decrease. The occurrence rate of phthisis every season had fluctuation with higher rate in middle two seasons and lower rate at the beginning and end. The major type of viral hepatitis was still hepatitis B. Patients with hand-foot-and-mouth disease were children under 5 years old accounting for 90.56%, mainly reported in May, June, July and August. At present, the condition of plague prevention for infectious diseases in Yantai is not optimistic with both new and old infectious diseases.

[Decomposition of different plant litters in Loess Plateau of Northwest China].

Taking the litters of species Hippophae rhamnoides, Medicago sativa, Populus simonii, Robinia pseudoacaci, Salix psammophila, and Stipa bungeana in the Loess Plateau of Northeast China as test objects, and by using mesh bags, this paper studied the dynamic changes of the litters mass, carbon, and nitrogen during decomposition after buried in the field in semiarid region. The litters buried were from one, two, or three of the plant species, and mixed thoroughly with equal proportion of masses. During decomposition, the mass loss rate, total carbon and nitrogen release rates, and total soluble carbon and nitrogen contents of different litters were higher at the early than at the later decomposition stage. After 412 d decomposition, the average mass loss rate of the litters was in the order of mixed litters of three plant species > mixed litters of two plant species > one plant species litter. By the end of this experiment, the average release rates of the litter total carbon and nitrogen ranked as one plant species litter > mixed litters of two plant species > mixed litters of three plant species, the litter soluble organic carbon content was mixed litters of two plant species > mixed litters of three plant species > one plant species litter, while the litter soluble total nitrogen content was mixed litters of three plant species > mixed litters of two plant species > one plant species litter. Correlation analysis showed that the litter mass loss rate had definite correlation with the litter soluble organic matter, especially soluble organic carbon. From the viewpoint of mass loss rate, the mixture of the litters of P. simonii, H. rhamnoide, and M. sativa was the optimum. It was suggested that in the process of returning farmland into forestland and grassland in the gully and valley region of Loess Plateau, it would be required to rationally increase plant species diversity to improve soil fertility.

1-(4-Cyano-benz-yl)-3,5-dimethyl-pyridinium bis-(benzene-1,2-dithiol-ato)nickelate(III).

The asymmetric unit of the title compound, (C(15)H(15)N(2))[Ni(C(6)H(4)S(2))(2)], contains half each of two independent centrosymmetric anions and a single cation in a general position. The Ni(III) ions are coordinated by four S atoms in a square-planar geometry. The anions exhibit two packing modes, viz. stacked along the a axis in a face-to-face fashion with an alternate arrangement of anions and cations, and stacked in a side-by-side fashion, forming ribbons parallel to (011).

Crystal structure of methyl parathion hydrolase from Pseudomonas sp. WBC-3.

Methyl parathion hydrolase (MPH, E.C.3.1.8.1), isolated from the soil-dwelling bacterium Pseudomonas sp. WBC-3, is a Zn(II)-containing enzyme that catalyzes the degradation of the organophosphate pesticide methyl parathion. We have determined the structure of MPH from Pseudomonas sp. WBC-3 to 2.4 angstroms resolution. The enzyme is dimeric and each subunit contains a mixed hybrid binuclear zinc center, in which one of the zinc ions is replaced by cadmium. In both subunits, the more solvent-exposed beta-metal ion is substituted for Cd2+ due to high cadmium concentration in the crystallization condition. Both ions are surrounded by ligands in an octahedral arrangement. The ions are separated by 3.5 angstroms and are coordinated by the amino acid residues His147, His149, Asp151, His152, His234 and His302 and a water molecule. Asp255 and a water molecule serve to bridge the zinc ions together. MPH is homologous with other metallo-beta-lactamases but does not show any similarity to phosphotriesterase that can also catalyze the degradation of methyl parathion with lower rate, despite the lack of sequence homology. Trp179, Phe196 and Phe119 form an aromatic cluster at the entrance of the catalytic center. Replacement of these three amino acids by alanine resulted in a significant increase of K(m) and loss of catalytic activity, indicating that the aromatic cluster has an important role to facilitate affinity of enzyme to the methyl parathion substrates.

Crystallization and preliminary X-ray studies of methyl parathion hydrolase from Pseudomonas sp. WBC-3.

Methyl parathion hydrolase (MPH) from Pseudomonas sp. WBC-3, an enzyme that catalyzes the degradation of methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate; MP), has been purified and crystallized by the hanging-drop vapour-diffusion method. The crystals were grown at 291 K using a precipitant solution consisting of 30% PEG 400, 0.1 M sodium acetate pH 4.6, 0.1 M CdCl(2). MPH is a zinc-containing enzyme judged by inductively coupled plasma mass-spectrometric (ICP-MS) analysis. Multiple-wavelength anomalous dispersive X-ray data were collected at 2.5 A resolution from a single crystal on beamline 41XU at SPring-8. The crystal belongs to space group P4(3)2(1)2, with unit-cell parameters a = 84.94, b = 84.94, c = 200.38 A, alpha = beta = gamma = 90 degrees. The asymmetric unit contains two molecules and has a solvent content of approximately 52%. Crystal structure determination is in progress.

Crystallization and preliminary crystallographic analysis of human serine dehydratase.

L-Serine dehydratase (SDH) catalyzes the pyridoxal phosphate (PLP) dependent deamination of L-serine to yield pyruvate. Recombinant human serine dehydratase was crystallized by the hanging-drop vapour-diffusion method. Crystals were grown at 291 K using (NH4)(2)SO4 as precipitant. Diffraction data were obtained to a resolution of 2.5 A from a single frozen crystal using Cu Kalpha radiation. The crystal belongs to space group I422, with unit-cell parameters a = 157.4, b = 157.4, c = 59.2 A, alpha = beta = gamma = 90 degrees. The asymmetric unit contains one molecule and has a solvent content of about 46%.