Relationship between domain-specific physical activity and cognitive function in older adults - findings from NHANES 2011-2014.

Objective: To determine the relationship between domain-specific physical activity (PA) (e.g., occupational PA [OPA], transport-related PA [TPA], and recreational PA [RPA]) and cognitive function in older adults. Methods: The data was obtained from the 2011-2014 cycle of the NHANES. We utilized weighted multivariate linear regression models among the included 2,924 people aged 60 years or older for our purposes. Results: RPA and total PA according to WHO guidelines were associated with verbal fluency (RPA ß: 1.400, 95% CI: 0.776, 2.024, p = 0.002; total PA ß: 1.115, 95% CI: 0.571, 1.659, p = 0.001), processing speed and executive function (RPA ß: 2.912, 95% CI. 1.291, 4.534, p = 0.005; total PA ß: 2.974, 95% CI: 1.683, 4.265, p < 0.001) were positively correlated, and total PA was correlated with delayed memory performance (ß: 0.254, 95% CI: 0.058, 0.449, p = 0.019). No significant association was observed between OPA, TPA, and various aspects of cognitive function among individuals over 60 years. Conclusion: There was no noteworthy correlation discovered between OPA and TPA in relation to cognitive function. However, RPA and total PA exhibited significant associations with verbal fluency, processing speed, and executive function. Additionally, maintaining PA levels ranging from 600 to 1,200 MET-min/week would yield the most favorable outcomes for cognitive function.

Modelling energy partition patterns of growing pigs fed diets with different net energy levels based on machine learning.

The objectives of this study were to evaluate the energy partition patterns of growing pigs fed diets with different net energy (NE) levels based on machine learning methods, and to develop prediction models for the NE requirement of growing pigs. Twenty-four Duroc × Landrace × Yorkshire crossbred barrows with an initial body weight of 24.90 ± 0.46 kg were randomly assigned to 3 dietary treatments, including the low NE group (2,325 kcal/kg), the medium NE group (2,475 kcal/kg), and the high NE group (2,625 kcal/kg). The total feces and urine produced from each pig during each period were collected, to calculate the NE intake, NE retained as protein (NEp), and NE retained as lipid (NEl). A total of 240 sets of data on the energy partition patterns of each pig were collected, 75% of the data in the dataset was randomly selected as the training dataset, and the remaining 25% was set as the testing dataset. Prediction models for the NE requirement of growing pigs were developed using algorithms including multiple linear regression (MR), artificial neural networks (ANN), k-nearest neighbor (K-NN), and random forest (RF), and the prediction performance of these models was compared on the testing dataset. The results showed pigs in the low NE group showed a lower average daily gain, lower average daily feed intake, lower NE intake, but greater feed conversion ratio compared to pigs in the high NE group in most growth stages. In addition, pigs in the three treatment groups did not show a significant difference in NEp in all growth stages, while pigs in the medium and high NE groups showed greater NEl compared to pig in the low NE group in growth stages from 25 to 55 kg (P < 0.05). Among the developed prediction models for NE intake, NEp, and NEl, the ANN models demonstrated the most optimal prediction performance with the smallest root mean square error (RMSE) and the largest R2, while the RF models had the worst prediction performance with the largest RMSE and the smallest R2. In conclusion, diets with varied NE concentrations within a certain range did not affect the NEp of growing pigs, and the models developed with the ANN algorithm could accurately achieve the NE requirement prediction in growing pigs.

A smart roof that transforms raindrops into agricultural spraying.

We present a smart roof that makes fragmented droplets from the impact of raindrops on superhydrophobic meshes and utilizes the droplets for agricultural spraying. This facile method transforms raindrops or waterdrops into uniform microdroplets, which can both reduce crop lodging induced by heavy rainfall, and realize uniform spraying of pesticides.

[Characteristics and Source Analysis of Volatile Organic Compounds in Typical Ozone Pollution Processes During Summer in Jinan, China].

Based on a typical ozone （O3） pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds （VOCs） during different pollution periods （clean period （CP）, pollution rise period （PRP）, heavy pollution period （HPP）, and pollution decline period （PDP）） in the urban area were analyzed. Both positive matrix factorization （PMF） and an observation-based model （OBM） were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρ（O3-8h） during the HPP period in the urban area was （246.67±11.24） µg·m-3, and ρ（O3-1h） had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds （OVOCs）, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential （OFP）. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals （HO2·ï¼‰ and methyl peroxide radicals （CH3O2·ï¼‰ with NO, and the net ozone generation rate during the HPP phase [P（O3）net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.

ATP-dependent citrate lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling of the Heart.

Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, Acly ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear. Methods: We utilized human heart tissue samples from healthy donor hearts and patients with hypertrophic cardiomyopathy. Further, we used CRISPR/Cas9 gene editing to inactivate Acly in cardiomyocytes of MyH6-Cas9 mice. In vivo, positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to the loss of ACL. We conducted a multi-omics analysis using RNA-sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. Results: Here, we show that in mice, ACL drives metabolic adaptation in the heart to sustain contractile function, histone acetylation, and lipid modulation. Notably, we show that loss of ACL increases glucose oxidation while maintaining fatty acid oxidation. Ex vivo isotope tracing experiments revealed a reduced efflux of glucose-derived citrate from the mitochondria into the cytosol, confirming that citrate is required for reductive metabolism in the heart. We demonstrate that YAP inactivation facilitates ACL deficiency. Computational flux analysis and integrative multi-omics analysis indicate that loss of ACL induces alternative isocitrate dehydrogenase 1 flux to compensate. Conclusions: This study mechanistically delineates how cardiac metabolism compensates for suppressed citrate metabolism in response to ACL loss and uncovers metabolic vulnerabilities in the heart.

Study on the multifunctional spatial-temporal evolution and coupling coordination of cultivated land: A case study of Hebei Province, China.

The rational use of cultivated land can guarantee food security and thus is highly important for ensuring social stability, economic development and national security. The current study investigated the multifunctional temporal and spatial variation characteristics of cultivated land and explored the spatial and temporal characteristics of the multifunction and coupling coordination degrees of cultivated land throughout Hebei Province. Based on the administrative division data, statistical yearbook data and land use status data of the impacted areas, a multifunctional evaluation index system of cultivated land was established. The CRITIC weight method and entropy weight method were used to determine the weight of the index, the comprehensive index model was used to determine the production, social security, ecology and landscape functions of cultivated land of Hebei Province in different periods, the coupling coordination model was used to explore the multifunctional coupling coordination degree of cultivated land in each county, and spatial autocorrelation analysis was performed to determine the correlation of the multifunctional coupling coordination degrees. From 2000 to 2020, the production, social security and landscape function of cultivated land in Hebei Province trended upward; the ecological function trended slightly downward. The multifunctional coupling coordination degree of cultivated land in Hebei Province trended significantly upward and changed from limited coordination to intermediate coordination. Furthermore, it exhibited strong agglomeration and a significant positive spatial correlation, forming a 'V'-type change rule of first decreasing and then increasing. Hebei Province exhibited remarkable spatial and temporal characteristics of the multifunction and coupling coordination degrees of cultivated land. Regions could thus customize different cultivated land functions to maximize the benefits of cultivated land use. The findings of this study may provide a scientific basis and theoretical support for sustainably using and managing cultivated land resources in areas with similar human geographical environments.

Myocardial Infarction Suppresses Protein Synthesis and Causes Decoupling of Transcription and Translation.

Gene expression involves transcription, translation, and mRNA and protein degradation. Advanced RNA sequencing measures mRNA levels for cell state assessment, but mRNA level does not fully reflect protein level. Identifying heart cell proteomes and their stress response is crucial. Using a cardiomyocyte-specific mouse model, we tracked protein synthesis after myocardial infarction. Our results showed that myocardial infarction suppresses protein synthesis and unveils a decoupling of translation and transcription regulation in cardiomyocytes.

Rapid in-situ calibration of computational micro-spectrometer with few-shot meta-learning.

Computational micro-spectrometers comprised of detector arrays and encoding structure arrays, such as on-chip Fabry-Perot (FP) cavity filters, have great potential in many in-situ applications owing to their compact size and snapshot imaging ability. Given manufacturing deviation and environmental influence are inevitable, easy and effective calibration for spectrometer is necessary, especially for in-situ applications. Currently calibration strategies based on iterative algorithms or neural networks require accurate measurements of pixel-level (spectral) encoding functions through monochromator or large amounts of standard samples. These procedures are time-consuming and expensive, thereby impeding in-situ applications. Meta-learning algorithms with few-shot learning ability can address this challenge by incorporating the prior knowledge in the simulated dataset. In this work, we propose a meta-learning algorithm free of measuring encoding function or large amounts of standard samples to calibrate a micro-spectrometer with manufacturing deviation effectively. Our micro-spectrometer comprises 16 types of FP filters covering a wavelength range of 550-720 nm. The center wavelength of each filter type deviates from the design up to 6 nm. After calibration with 15 different color data, the average reconstruction error on the test dataset decreased from 7.2 × 10-3 to 1.2 × 10-3, and further decreased to 9.4 × 10-4 when the calibration data increased to 24. The performance is comparable to algorithms trained with measured encoding function both in reconstruction error and generalization ability. We estimated that the cost of in-situ calibration through reflectance measurements of color chart decreased to one percent of the cost through monochromator measurements. By exploiting prior deviation information in simulation data with meta-learning, the efficiency and cost of calibration are significantly improved, thereby facilitating the large-scale production and in-situ application of micro-spectrometers.

Plasmonic hotspot arrays boost second harmonic generation in thin-film lithium niobate.

Focusing light down to subwavelength scales to enhance the light-matter interaction has been highly sought after, which has promoted significant researches and applications in nanophotonics. Plasmonic nanoantennae are a significant tool to achieve this goal since they can confine light into ultra-small volumes far below the diffraction limit. However, metallic materials have the property of central symmetry, resulting in weak second-order nonlinear effects. Here, we design plasmonic bowtie nanoantennae on thin-film lithium niobate (TFLN) for deep-subwavelength light confinement to boost the second-harmonic generation (SHG) in TFLN via the plasmonic hotspot enhancement. The SHG enhancement factor of about 20 times as compared to unpatterned TFLN is achieved in the experiment when resonantly excited by femtosecond laser. This work proposes a route for subwavelength nonlinear optics on the TFLN platform.

Vapor Pressure and Enthalpy of Vaporization of Guanidinium Methanesulfonate as a Phase Change Material for Thermal Energy Storage.

This paper reports the vapor pressure and enthalpy of vaporization for a promising phase change material (PCM) guanidinium methanesulfonate ([Gdm][OMs]), which is a typical guanidinium organomonosulfonate that displays a lamellar crystalline architecture. [Gdm][OMs] was purified by recrystallization. The elemental analysis and infrared spectrum of [Gdm][OMs] confirmed the purity and composition. Differential scanning calorimetry (DSC) also confirmed its high purity and showed a sharp and symmetrical endothermic melting peak with a melting point (Tm) of 207.6 °C and a specific latent heat of fusion of 183.0 J g-1. Thermogravimetric analysis (TGA) reveals its thermal stability over a wide temperature range, and yet three thermal events at higher temperatures of 351 °C, 447 °C, and 649 °C were associated with vaporization or decomposition. The vapor pressure was measured using the isothermogravimetric method from 220 °C to 300 °C. The Antoine equation was used to describe the temperature dependence of its vapor pressure, and the substance-dependent Antoine constants were obtained by non-linear regression. The enthalpy of vaporization (ΔvapH) was derived from the linear regression of the slopes associated with the linear temperature dependence of the rate of weight loss per unit area of vaporization. Hence, the temperature dependence of vapor pressures ln Pvap (Pa) = 10.99 - 344.58/(T (K) - 493.64) over the temperature range from 493.15 K to 573.15 K and the enthalpy of vaporization ΔvapH = 157.10 ± 20.10 kJ mol-1 at the arithmetic mean temperature of 240 °C were obtained from isothermogravimetric measurements using the Antoine equation and the Clausius-Clapeyron equation, respectively. The flammability test indicates that [Gdm][OMs] is non-flammable. Hence, [Gdm][OMs] enjoys very low volatility, high enthalpy of vaporization, and non-flammability in addition to its known advantages. This work thus offers data support, methodologies, and insights for the application of [Gdm][OMs] and other organic salts as PCMs in thermal energy storage and beyond.

Characteristic substance analysis and rapid detection of bacteria spores in cooked meat products by surface enhanced Raman scattering based on Ag@AuNP array substrate.

BACKGROUND: Bacterial spores are the main potential hazard in medium- and high-temperature sterilized meat products, and their germination and subsequent reproduction and metabolism can lead to food spoilage. Moreover, the spores of some species pose a health and safety threat to consumers. The rapid detection, prevention, and control of bacterial spores has always been a scientific problem and a major challenge for the medium and high-temperature meat industry. Early and sensitive identification of spores in meat products is a decisive factor in contributing to consumer health and safety. RESULTS: In this study, we developed a novel and stable Ag@AuNP array substrate by using a two-step synthesis approach and a liquid-interface self-assembly method that can directly detect bacterial spores in actual meat product samples without the need for additional in vitro bacterial culture. The results indicate that the Ag@AuNP array substrate exhibits high reproducibility and Raman enhancement effects (1.35 × 105). The differentiation in the Surface enhanced Raman scattering (SERS) spectra of five bacterial spores primarily arises from proteins in the spore coat and inner membrane, peptidoglycan of cortex, and Ca2⁺-DPA within the spore core. The correct recognition rate of linear discriminant analysis for spores in the meat product matrix can reach 100 %. The average recovery accuracy of the SERS quantitative model was at around 101.77 %, and the limit of detection can reach below 10 CFU/mL. SIGNIFICANCE: It provides a promising technological strategy for the characteristic substance analysis and timely monitoring of spores in meat products.

Probiotic Bacillus as fermentation agents: Status, potential insights, and future perspectives.

Probiotic Bacillus strains can solve the problems of single flavor and long fermentation time of fermented products caused by the lack of certain functional genes and insufficient metabolism ability of fermenter strains (Lactobacillus and Bifidobacterium) at the present stage. There is a lack of systematic evaluation and review of probiotic Bacillus as food fermentation agents. In this paper, it is observed that probiotic Bacillus strains are involved to varying degrees in liquid-state, semi-solid state, and solid-state fermentation and are widely present in solid-state fermented foods. Probiotic Bacillus strains not only produce abundant proteases and lipases, but also effective antifungal lipopeptides and extracellular polymers, thus enhancing the flavor, nutritional value and safety of fermented foods. Bacillus with probiotic qualities is an underutilized group of probiotic food fermentation agents, which give a potential for the development of fermentation technology in the food business and the integration of ancient traditional fermentation techniques.

Self-Powered Traffic Lights Through Wind Energy Harvesting Based on High-Performance Fur-Brush Dish Triboelectric Nanogenerators.

Traffic lights play vital roles in urban traffic management systems, providing clear directional guidance for vehicles and pedestrians while ensuring traffic safety. However, the vast quantity of traffic lights widely distributed in the transportation system aggravates energy consumption. Here, a self-powered traffic light system is proposed through wind energy harvesting based on a high-performance fur-brush dish triboelectric nanogenerator (FD-TENG). The FD-TENG harvests wind energy to power the traffic light system continuously without needing an external power supply. Natural rabbit furs are applied to dish structures, due to their outstanding characteristics of shallow wear, high performance, and resistance to humidity. Also, the grid pattern of the dish structure significantly impacts the TENG outputs. Additionally, the internal electric field and the influences of mechanical and structural parameters on the outputs are analyzed by finite element simulations. After optimization, the FD-TENG can achieve a peak power density of 3.275 W m-3. The portable and miniature features of FD-TENG make it suitable for other natural environment systems such as forests, oceans, and mountains, besides the traffic light systems. This study presents a viable strategy for self-powered traffic lights, establishing a basis for efficient environmental energy harvesting toward big data and Internet of Things applications.

Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.

PURPOSE: To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). METHODS: The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. RESULTS: OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421-/- mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. CONCLUSIONS: OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

Spatially resolved transcriptomic profiling of placental development in dairy cow.

The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

Simulation evaluation of a single-photon laser methane remote sensor for leakage rate monitoring.

We propose a novel methane leakage rate remote sensor that combines a single-photon avalanche diode detector with a near-infrared 1653.7 nm low-power laser. The proposed M sequence and triangle wave signal modulation method simultaneously realizes the detection of methane leakage and target point clouds. Innovatively, the sensor's methane concentration and leakage rate quantification ability were simulated by combining the Gaussian plume diffusion model and the Risley prism. The effects of the prism rotation ratio, wind speed, leakage rate, atmospheric stability (AS), target reflectivity, signal averaging period, and concentration spatial interpolation method on leakage rate are discussed. When plume methane concentrations reduce from 10,000 to 500 ppm·m, the relative concentration bias rise from 1% to 30%, the absolute concentration bias is approximately 100 ppm·m. Two spatial concentration interpolation methods introduced leakage rate bias ranging from 6%-25%. For a low AS, the leakage rate bias under the cubic interpolation method was small (approximately 1.6%). In addition, when the initial leakage rate increased from 100 to 1,000 mg/s, the leakage rate bias was approximately 20% smaller.

Highly sensitive mid-infrared methane remote sensor using a deep neural network filter.

A novel mid-infrared methane remote sensor integrated on a movable platform based on a 3.291-µm interband cascade laser (ICL) and wavelength modulation spectroscopy (WMS) is proposed. A transmitting-receiving coaxial, visualized optical layout is employed to minimize laser energy loss. Using a hollow retro-reflector remotely deployed as a cooperative target, the atmospheric average methane concentration over a 100-meter optical range is measured with high sensitivity. A deep neural network (DNN) filter is used for second harmonic (2f) signal denoising to compensate for the performance shortcomings of conventional filtering. Allan deviation analysis indicated that after applying the DNN filter, the limit of detection (LOD) of methane was 86.62 ppb with an average time of 1 s, decreasing to 12.03 ppb with an average time of 229 s, which is a significant promotion compared to similar work reported. The high sensitivity and stability of the proposed sensor are shown through a 24-hour continuous monitoring experiment of atmospheric methane conducted outdoors, providing a new solution for high-sensitivity remote sensing of atmospheric methane.

Pharmacokinetics of Enrofloxacin in Plasma, Urine, and Feces of Donkey (Equus asinus) after a Single Intragastric Administration.

Enrofloxacin is a broad-spectrum antimicrobial agent, but the study of its pharmacokinetics/pharmacodynamics (PKs/PDs) in donkeys is rarely reported. The present study aimed to investigate the pharmacokinetics of enrofloxacin administered intragastrically, and to study the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in plasma, urine, and feces, and the PK/PD parameters were investigated to provide a rationale for enrofloxacin treatment in donkeys. A total of five healthy donkeys were selected for intragastric administration of 7.5 mg·kg-1 BW of enrofloxacin by gavage, and blood, urine, and fecal samples were collected. The results showed that the elimination half-life of plasma enrofloxacin was 11.40 ± 6.40 h, Tmax was 0.55 ± 0.12 h, Cmax was 2.46 ± 0.14 mg·L-1, AUC0-∞ was 10.30 ± 3.37 mg·L-1·h, and mean residence time (MRT) was 7.88 ± 1.26 h. The Tmax of plasma ciprofloxacin was 0.52 ± 0.08 h, Cmax was 0.14 ± 0.03 mg·L-1, and AUC0-∞ was 0.24 ± 0.16 mg·L-1·h. Urinary Cmax was 38.18 ± 8.56 mg·L-1 for enrofloxacin and 15.94 ± 4.15 mg·L-1 for ciprofloxacin. The total enrofloxacin and ciprofloxacin recovered amount in urine was 7.09 ± 2.55% of the dose for 144 h after dosing. The total enrofloxacin and ciprofloxacin recovered amount in feces was 25.73 ± 10.34% of the dose for 144 h after dosing. PK/PD parameters were also examined in this study, based on published MICs. In conclusion, 7.5 mg/kg BW of enrofloxacin administered intragastrically to donkeys was rapidly absorbed, widely distributed, and slowly eliminated in their bodies, and was predicted to be effective against bacteria with MICs < 0.25 mg·L-1.

Disturbed flow impairs MerTK-mediated efferocytosis in aortic endothelial cells during atherosclerosis.

Background: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for efferocytosis, a process for the clearance of apoptotic cells. MerTK is mainly expressed in macrophages and immature dendritic cells. There are very limited reports focused on MerTK biology in aortic endothelial cells (ECs). It remains unclear for the role of blood flow patterns in regulating MerTK-mediated efferocytosis in aortic ECs. This study was designed to investigate whether endothelial MerTK and EC efferocytosis respond to blood flow patterns during atherosclerosis. Methods: Big data analytics, RNA-seq and proteomics combined with our in vitro and in vivo studies were applied to reveal the potential molecular mechanisms. Partial carotid artery ligation combined with AAV-PCSK9 and high fat diet were used to set up acute atherosclerosis in 4 weeks. Results: Our data showed that MerTK is sensitive to blood flow patterns and is inhibited by disturbed flow and oscillatory shear stress in primary human aortic ECs (HAECs). The RNA-seq data in HAECs incubated with apoptotic cells showed that d-flow promotes pro-inflammatory pathway and senescence pathway. Our in vivo data of proteomics and immunostaining showed that, compared with WT group, MerTK-/- aggravates atherosclerosis in d-flow areas through upregulation of endothelial dysfunction markers (e.g. IL-1ß, NF-κB, TLR4, MAPK signaling, vWF, VCAM-1 and p22phox) and mitochondrial dysfunction. Interestingly, MerTK-/-induces obvious abnormal endothelial thickening accompanied with decreased endothelial efferocytosis, promoting the development of atherosclerosis. Conclusions: Our data suggests that blood flow patterns play an important role in regulating MerTK-mediated efferocytosis in aortic ECs, revealing a new promising therapeutic strategy with EC efferocytosis restoration to against atherosclerosis.

Identification of the ferroptosis-related prognostic gene signature in mesothelioma.

Mesothelioma, an uncommon yet highly aggressive malignant neoplasm, presents challenges in the effectiveness of current therapeutic approaches. Ferroptosis, a non-apoptotic mechanism of cellular demise, exhibits a substantial association with the progression of diverse cancer forms. It is important to acknowledge that there exists a significant association between ferroptosis and the advancement of various forms of cancer. Nevertheless, the precise role of ferroptosis regulatory factors within the context of mesothelioma remains enigmatic. In our investigation, we initially scrutinized the prognostic significance of 24 ferroptosis regulatory factors in the realm of mesothelioma. Our observations unveiled that heightened expression levels of CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, coupled with reduced DPP4 expression, were indicative of an unfavorable prognosis. Built upon the nine previously discussed prognostic genes, the ferroptosis prognostic model offers a reliable means to forecast mesothelioma patients' survival with a substantial degree of precision. Furthermore, a notable correlation emerged between these prognostic ferroptosis regulators and parameters such as immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression in the context of mesothelioma. Within this cadre of nine ferroptosis regulatory factors with prognostic relevance, FANCD2 exhibited the most pronounced prognostic influence, as elucidated by our analyses. Subsequently, we executed a validation process employing clinical specimens sourced from our institution, thus confirming that heightened FANCD2 expression is a discernible harbinger of an adverse prognosis in the context of mesothelioma. In vitro experiments revealed that knocking down FANCD2 markedly suppressed the proliferation, migration, and ability of mesothelioma cells to attract immune cells. Furthermore, our findings also showed that reducing FANCD2 levels heightened the vulnerability of mesothelioma cells to inducers of ferroptosis. Furthermore, an extensive pan-cancer analysis uncovered a robust association between FANCD2 and the gene expression linked to immune checkpoints, thereby signifying an adverse prognosis across a broad spectrum of cancer types. Additional research is warranted to validate these findings.