Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Nanyang Cattle.

The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 µg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 µg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.

[Effects of acupuncture on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats].

OBJECTIVE: To observe the effects of acupuncture at "antihypertensive acupoint prescription" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension. METHODS: Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the "antihypertensive acupoint prescription" (bilateral "Renying" [ST 9], "Quchi" [LI 11], "Zusanli" [ST 36], "Taichong" [LR 3] and "Neiguan" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA). RESULTS: Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05). CONCLUSION: Acupuncture at "antihypertensive acupoint prescription" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.

Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

Background: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.

Pazopanib attenuated bleomycin-induced pulmonary fibrosis via suppressing TGF-ß1 signaling pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma. Methods: In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis. Results: In vivo experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that pazopanib suppressed transforming growth factor-ß1 (TGF-ß1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-ß1/Smad and non-Smad signaling pathways during fibroblast activation. Conclusions: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-ß1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-ß1/Smad signal route and the TGF-ß1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Radiation polymerization for the preparation of universal coatings: remarkable anti-fogging and frost-resisting performance.

Hydrophilic anti-fogging coatings have attracted considerable attention due to their ease of preparation and excellent fog resistance. In this study, a hydrophilic anti-fogging coating based on the random copolymer p(AA-co-SAS) was prepared using acrylic acid (AA) and sodium allylsulfonate (SAS) as monomers through radiation polymerization. The introduction of SAS successfully transformed the random copolymer from a gel state into a film-forming polymer solution. The presence of AA structural units in p(AA-co-SAS) improved the film-forming properties of the polymer solution. Additionally, there was a positive correlation between the proportion of SAS structural units in the random copolymer and the scratch hardness and wetting properties of the coating. After coating polycarbonate (PC) sheets, the surface hydrophilicity was significantly enhanced, with the contact angle of PC-AA10/SAS5 decreasing from 100.1° to 18.8° within 50 seconds. The outstanding wetting properties endowed the coating with exceptional anti-fogging and frost-resisting performance. It exhibited optimal transparency under both testing conditions and demonstrated good stability during cyclic testing. Tape adhesion tests indicated that the adhesion between the coating and PC reached a 5B level. When AA10/SAS5 was applied to PET film, glass, and PMMA goggles, all samples showed excellent anti-fog performance. Even after being naturally placed for one year under ambient conditions, the PMMA goggles still maintained good performance in the anti-fog and frost resistance tests. The remarkable comprehensive properties of the polymer coating based on p(AA-co-SAS) suggest enormous potential applications in industries such as packaging, healthcare, and optical equipment.

Resolution-increased fiber-optic strain sensor with a large dynamic range driven by white light.

The white light interferometer is advantageous for wavelength division multiplexing (WDM), but the excessive noise floor limits its application in practicality. In this Letter, we propose a fiber-optic sensor driven by a broadband light source, which uses a fiber-optic Fabry-Perot cavity and a reference interferometer to enhance strain resolution. In the experiment, the strain resolution of a 5.86 m resonant sensor is 18.5 fɛ/H z at 1.5 kHz, while the maximum detectable signal is over 230 rad at 1 kHz. With low cost, this method provides a new, to the best of our knowledge, solution for WDM sensing arrays with a large dynamic range.

Enzyme Engineering Renders Chlorinase the Activity of Fluorinase.

Organofluorine compounds have attracted substantial attention owing to their wide application in agrochemistry. Fluorinase (FlA) is a unique enzyme in nature that can incorporate fluorine into an organic molecule. Chlorinase (SalL) has a similar mechanism as fluorinase and can use chloride but not fluoride as a substrate to generate 5'-chloro-deoxyadenosine (5'-ClDA) from S-adenosyl-l-methionine (SAM). Therefore, identifying the features that lead to this selectivity for halide ions is highly important. Here, we engineered SalL to gain the function of FlA. We found that residue Tyr70 plays a key role in this conversion through alanine scanning. Site-saturation mutagenesis experiments demonstrated that Y70A/C/S/T/G all exhibited obvious fluorinase activity. The G131S mutant of SalL, in which the previously thought crucial residue Ser158 for fluoride binding in FlA was introduced, did not exhibit fluorination activity. Compared with the Y70T single mutant, the double mutant Y70T/W129F increased 5'-fluoro-5-deoxyadenosine (5'-FDA) production by 76%. The quantum mechanics (QM)/molecular mechanics (MM) calculations suggested that the lower energy barriers and shorter nucleophilic distance from F- to SAM in the mutants than in the SalL wild-type may contribute to the activity. Therefore, our study not only renders SalL the activity of FlA but also sheds light on the enzyme selectivity between fluoride versus chloride.

Delay on detection, and diagnosis of pulmonary tuberculosis and the influencing factors in Inner Mongolia students during 2011-2022 / 中国学校卫生

Objective@#To analyze the delay on detection, care seeking, diagnosis and treatment of tuberculosis among students in Inner Mongolia Autonomous Region (Inner Mongolia) from 2011 to 2022 and its influencing factors, so as to provide support for the prevention and treatment of tuberculosis among students.@*Methods@#The general demographic indicators of students with tuberculosis in Inner Mongolia from January 1, 2011 to December 31, 2022 were collected from the infectious disease monitoring (new) module of the China Disease Prevention and Control Information System. General characteristics and trend of four types of delayed pulmonary tuberculosis patients in students were analyzed. The influencing factors were analyzed using univariate and multivariate Logistic regressions.@*Results@#From 2011 to 2022, there were 6 032 cases of pulmonary tuberculosis among students in Inner Mongolia. The rates of delayed detection, delayed care seeking, delayed diagnosis, and delayed treatment were 51.71%, 64.01%, 7.82 %, and 2.30%, respectively. The results of multivariate Logistic regression analysis showed that tracking ( OR =1.51) in the patient source,league level diagnosis ( OR =3.16) in the diagnostic institution level,and county level diagnosis ( OR =2.41) were positively associated with delayed discovery ( P <0.05). At the level of diagnostic unit, league city level diagnosis ( OR =2.69), and county level diagnosis ( OR =3.67) associated with more delayed care seeking ( P <0.05). Referral ( OR =1.58) and follow up ( OR =2.55), floating population ( OR =2.05), further consultation with a doctor ( OR =2.11), and no results in imaging manifestations ( OR =2.19) were positively associated with delayed diagnosis( P <0.05). The factors contributing to delayed treatment were referral ( OR =1.84), follow up ( OR =4.91), active screening ( OR =5.46), and floating population( OR =1.95)( P <0.05).@*Conclusions@#From 2011 to 2022, the delay on detection and care seeking for tuberculosis patients among students in Inner Mongolia is at a relatively high level, while the delay in diagnosis and treatment is at a relatively low level but shows an increasing trend. It is necessary to focus on the factors associated with delays in identification, diagnosis and treatment in tuberculosis outbreak in the context of school to prevent or reduce school tuberculosis outbreak.