Efficacy and Safety of Minimally Invasive Neuroendoscopic Surgery in the Therapy of Supratentorial Hypertensive Intracerebral Hemorrhage: A Meta-Analysis.

OBJECTIVE: To systematically investigate the therapeutic effects of neuroendoscopic (NE) surgery in supratentorial hypertensive intracerebral hemorrhage (HICH), including key indicators such as hematoma evacuation rate, complications, and neurological prognosis, thus comprehensively understanding the superiority of NE surgery in supratentorial HICH therapy, and to provide scientific basis and decision-making support for clinical practice. METHODS: The PubMed, EMBASE, Cochrane, Google, and CNKI databases were searched for relevant literature related to NE surgery for supratentorial HICH published before October 2023. Summary analyses of hematoma evacuation rate, mortality, clinical treatment, good functional outcome (Glasgow Outcome Scale, Glasgow Coma Scale, and modified Rankin Scale), and postoperative complications in the NE group were performed, and Revman 5.3 was used to conduct the meta-analysis. RESULTS: Fourteen trials with 1266 patients were enrolled in this meta-analysis, with an overall moderate risk of bias. Compared with craniotomy, NE-treated patients had a higher rate of cerebral hematoma evacuation, and their operative time, intraoperative blood loss, and hospital stay were markedly reduced. Moreover, NE surgery could better restore patients' neurological function and autonomy, presenting a higher Glasgow Outcome Scale, Glasgow Coma Scale, and a lower modified Rankin Scale. Moreover, NE surgery effectively reduced the incidence of mortality and postoperative complications, especially rebleeding and lung infection. CONCLUSION: Neuroendoscopic surgery not only better removes intracranial hematomas and improves neurological function and autonomy in supratentorial HICH patients, but also effectively reduces mortality and postoperative complications.

Acoustic black hole ultrasonic scalpel.

Ultrasonic scalpels (USs), as the preferred energy instruments, are facing a growing need to exhibit enhanced performance with the diversification of modern surgical challenges. Hence, we proposed an acoustic black hole ultrasonic scalpel (ABHUS) in longitudinal-bending coupled vibration for efficient surgical cutting. By incorporating an acoustic black hole profile, the local bending wave velocity is reduced and the amplitude is amplified cumulatively, thus creating a high-energy region near the blade tip to enhance the cutting performance of the ABHUS. The precise physical analysis model is established for systematic design of the ABHUS and quick estimation of its frequency characteristics. The vibration simulation and experiments demonstrate that compared with the conventional ultrasonic scalpel (CUS), the output amplitude of the ABHUS significantly increases, particularly a 425% increase in bending vibration displacement. The in-vitro cutting experiment confirms that ABHUS exhibits superior cutting performance. Our design presents vast possibilities and potential for the development of high-performance ultrasonic surgical instruments, serving as an innovative supplement with extraordinary significance for application of acoustic black holes.

Simultaneous detection of 10 cancer-associated amino acids and polyamines by high-performance liquid chromatography-high resolution mass spectrometry in pleural effusion cells obtained from lung adenocarcinoma patients.

The deregulation of amino acid and polyamine metabolism is a hallmark of malignancy that regulates cancer cell proliferation, angiogenesis, and invasion. A sensitive mass spectrometry method was developed to simultaneously quantify 10 cancer-associated metabolites in pleural effusion cells for the diagnosis of malignancy and to complement conventional pleural cytology. Analytes were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) using C8-reversed-phase HPLC for separation and sequential window acquisition of all theoretical fragment ion spectra (SWATH) acquisition for obtaining high-resolution quantitative MS/MS chromatograms. This method was validated and applied to pleural effusion cells from patients with lung adenocarcinoma (LUAD, n = 48) and those from benign controls (n = 23). The range of the above metabolites was 2-200 ng/mL for proline, aspartate, ornithine, creatine, glutamine, glutamate, arginine, citrulline, and spermine and 10-1000 ng/mL for putrescine. The intra-assay and inter-assay coefficient of variation was below 13.70 % for all analytes. The joint detection of these metabolites in pleural effusion cells achieved a clinical sensitivity of 75.0 % and specificity of 95.7 % differentiating LUAD patients from benign controls. This assay enabled the detection of 10 cancer-associated metabolites in pleural effusion cells, and the increased concentration of these metabolites was correlated with the presence of LUAD.

Improved Particle Filter Algorithm for Multi-Target Detection and Tracking.

In modern radar detection systems, the particle filter technique has become one of the core algorithms for real-time target detection and tracking due to its good nonlinear and non-Gaussian system state estimation capability. However, when dealing with complex dynamic scenes, the traditional particle filter algorithm exposes obvious deficiencies. The main expression is that the sample degradation is serious, which leads to a decrease in estimation accuracy. In multi-target states, the algorithm is difficult to effectively distinguish and stably track each target, which increases the difficulty of state estimation. These problems limit the application potential of particle filter technology in multi-target complex environments, and there is an urgent need to develop a more advanced algorithmic framework to enhance its robustness and accuracy in complex scenes. Therefore, this paper proposes an improved particle filter algorithm for multi-target detection and tracking. Firstly, the particles are divided into tracking particles and searching particles. The tracking particles are used to maintain and update the trajectory information of the target, and the searching particles are used to identify and screen out multiple potential targets in the environment, to sufficiently improve the diversity of the particles. Secondly, the density-based spatial clustering of applications with noise is integrated into the resampling phase to improve the efficiency and accuracy of particle replication, so that the algorithm can effectively track multiple targets. Experimental result shows that the proposed algorithm can effectively improve the detection probability, and it has a lower root mean square error (RMSE) and a stronger adaptability to multi-target situation.

Roles of soil minerals in the degradation of chlorpyrifos and its intermediate by microwave activated peroxymonosulfate.

Soil mineral is one of the important factors that affecting oxidant decomposition and pollutants degradation in soil remediation. In this study, the effects of iron minerals, manganese minerals and clay minerals on the degradation of chlorpyrifos (CPF) and its intermediate product 3,5,6-trichloro-2-pyridinol (TCP) by microwave (MW) activated peroxymonosulfate (PMS) were investigated. As a result, the addition of minerals had slight inhibitory effect on the degradation efficiency of CPF by MW/PMS, but the degradation efficiency of TCP was improved by the addition of some specific minerals, including ferrihydrite, birnessite, and random symbiotic mineral of pyrolusite and ramsdellite (Pyr-Ram). The stronger MW absorption ability of minerals is beneficial for PMS decomposition, but the MW absorption ability of minerals cannot be fully utilized because of the weaker MW radiation intensity under constant temperature conditions. Through electron spin resonance test, quenching experiment and electrochemical experiment, electron transfer, SO4- and OH, SO4- dominated TCP degradation by MW/PMS with the addition of birnessite, Pyr-Ram and ferrihydrite, respectively. Besides, the adsorption effect of ferrihydrite also enhanced the removal of TCP. The redox of Mn (III)/Mn (IV) or Fe (II)/Fe (III) in manganese/iron minerals participated in the generation of reactive species. In addition, the addition of minerals not only increased the variety of alkyl hydroxylation products of CPF, causing different degradation pathways from CPF to TCP, but also further degraded TCP to dechlorination or hydroxylation products. This study demonstrated the synergistic effect of minerals and MW for PMS activation, provided new insights for the effects of soil properties on soil remediation by MW activated PMS technology.

Sidewall Corrugation-Modulated Phase-Apodized Silicon Grating Filter.

In this work, phase-apodized silicon grating filters with varying sidewall corrugation width and location were investigated, while the resonance wavelength, extinction ratio, and rejection bandwidth were tuned flexibly. The grating filters with a waveguide width of 500 nm and grating period of 400 nm were fabricated and characterized as a proof of concept. The resonance wavelength of the device can be shifted by 4.54 nm by varying the sidewall corrugation width from 150 to 250 nm. The corresponding rejection bandwidth can be changed from 1.19 to 2.03 nm by applying a sidewall corrugation location offset from 50 to 200 nm. The experimental performances coincide well with the simulation results. The presented sidewall corrugation-modulated apodized grating can be expected to have great application prospects for optical communications and semiconductor lasers.

Mechanochemical remediation of contaminated soil: A review.

Mechanochemical techniques have been garnering growing attention in remediation of contaminated soil. This paper summarizes the performance, mechanism, influential factors, and environmental impacts of mechanochemical remediation (MCR) for persistent organic pollutants (POPs) contaminated soil and heavy metal(loid) s (HMs) contaminated soil. Firstly, in contrast to other technologies, MCR can achieve desirable treatment of POPs, HMs, and co-contaminated soil, especially with high-concentration pollutants. Secondly, POPs undergo mineralization via interaction with mechanically activated substances, where aromatic and aliphatic pollutants in soil may go through varied degradation routes; inorganic pollutants can be firmly combined with soil particles by fragmentation and agglomeration induced by mechanical power, during which additives may enhance the combination but their contact with anionic metal(loid)s may be partially suppressed. Thirdly, the effect of MCR primarily hinges on types of milling systems, the accumulation of mechanical energy, and the use of reagents, which is basically regulated through operating parameters: rotation speed, ball-to-powder ratio, reagent-to-soil ratio, milling time, and soil treatment capacity; minerals like clay, metal oxides, and sand in soil itself are feasible reagents for remediation, and alien additives play a crucial role in synergist and detoxification; additionally, various physicochemical properties of soil might influence the mechanochemical effect to varying degrees, yet the key influential performance and mechanism remain unclear and require further investigation. Concerning the assessment of soil after treatment, attention needs to be paid to soil properties, toxicity of POPs' intermediates and leaching HMs, and long-term appraisement, particularly with the introduction of aggressive additives into the system. Finally, proposals for current issues and forthcoming advancements in this domain are enumerated in items. This review provides valuable insight into mechanochemical approaches for performing more effective and eco-friendly remediation on contaminated soil.

Distinct compositions and functions of circulating microbial DNA in the peripheral blood compared to fecal microbial DNA in healthy individuals.

The crucial function of circulating microbial DNA (cmDNA) in peripheral blood is gaining recognition because of its importance in normal physiology and immunity in healthy individuals. Evidence suggests that cmDNA in peripheral blood is derived from highly abundant, translocating gut microbes. However, the associations with and differences between cmDNA in peripheral blood and the gut microbiome remain unclear. We collected blood, urine, and fecal samples from volunteers to compare their microbial information via 16S rDNA sequencing. The results revealed that, compared with gut microbial DNA, cmDNA in peripheral blood was associated with reduced diversity and a distinct microbiota composition. The cmDNA in the blood reflects the biochemical processes of microorganisms, including synthesis, energy conversion, degradation, and adaptability, surpassing that of fecal samples. Interestingly, cmDNA in blood showed a limited presence of DNA from anaerobes and gram-positive bacteria, which contrast with the trend observed in fecal samples. Furthermore, analysis of cmDNA revealed traits associated with mobile elements and potential pathologies, among others, which were minimal in stool samples. Notably, cmDNA analysis indicated similarities between the microbial functions and phenotypes in blood and urine samples, although greater diversity was observed in urine samples. Source Tracker analysis suggests that gut microbes might not be the main source of blood cmDNA, or a selective mechanism allows only certain microbial DNA into the bloodstream. In conclusion, our study highlights the composition and potential functions associated with cmDNA in peripheral blood, emphasizing its selective presence; however, further research is required to elucidate the mechanisms involved.IMPORTANCEOur research provides novel insights into the unique characteristics and potential functional implications of circulating microbial DNA (cmDNA) in peripheral blood. Unlike other studies that analyzed sequencing data from fecal or blood microbiota in different study cohorts, our comparative analysis of cmDNA from blood, urine, and fecal samples from the same group of volunteers revealed a distinct blood-specific cmDNA composition. We discovered a decreased diversity of microbial DNA in blood samples compared to fecal samples as well as an increased presence of biochemical processes microbial DNA in blood. Notably, we add to the existing knowledge by documenting a reduced abundance of anaerobes and gram-positive bacteria in blood compared to fecal samples according to the analysis of cmDNA and gut microbial DNA, respectively. This observation suggested that a potential selective barrier or screening mechanism might filter microbial DNA molecules, indicating potential selectivity in the translocation process which contrasts with the traditional view that cmDNA primarily originates from random translocation from the gut and other regions. By highlighting these differences, our findings prompt a reconsideration of the origin and role of cmDNA in blood circulation and suggest that selective processes involving more complex biological mechanisms may be involved.

Comprehensive insight into mercury contamination in atmospheric, terrestrial and aquatic ecosystems surrounding a typical antimony-coal mining district.

This study comprehensively investigated mercury (Hg) contents of various environmental compartments in a typical antimony-coal mining area with intensive industrial activities over the past 120 years to analyze Hg environmental behaviors and evaluate Hg risks. The total mercury (THg) contents in river water, sediments, soils, PM10, dust falls, vegetables and corns were 1.16 ± 0.63 µg/L, 2.01 ± 1.64 mg/kg, 1.87 ± 3.88 mg/kg, 7.87 ± 18.68 ng/m3, 13.01 ± 14.53 mg/kg, 0.30 ± 0.34 mg/kg and 3.11 ± 0.51 µg/kg, respectively. The δ202Hg values in soils and dust falls were - 1.58 ∼ 0.12‰ and 0.25 ∼ 0.30‰, respectively. Environmental samples affected by industrial activities in the Xikuangshan (XKS) presented higher THg and δ202Hg values. Binary mixing model proved that atmospheric deposition with considerable Hg deposition flux (0.44 ∼ 6.40, 3.12 ± 2.20 mg/m2/y) in the XKS significantly contributed to Hg accumulations on surface soils. Compared with soils, sediments with more frequent paths and higher burst probabilities presented higher dynamic Hg risks. Children were faced higher health risk of multiple Hg exposure than adults. Furthermore, the health risk of THg by consuming leaf vegetables deserved more attention. These findings provided scientific basis for managing Hg contamination.

Identification of Driver Status Hazard Level and the System.

According to the survey statistics, most traffic accidents are caused by the driver's behavior and status irregularities. Because there is no multi-level dangerous state grading system at home and abroad, this paper proposes a complex state grading system for real-time detection and dynamic tracking of the driver's state. The system uses OpenMV as the acquisition camera combined with the cradle head tracking system to collect the driver's current driving image in real-time dynamically, combines the YOLOX algorithm with the OpenPose algorithm to judge the driver's dangerous driving behavior by detecting unsafe objects in the cab and the driver's posture, and combines the improved Retinaface face detection algorithm with the Dlib feature-point algorithm to discriminate the fatigue driving state of the driver. The experimental results show that the accuracy of the three driver danger levels (R1, R2, and R3) obtained by the proposed system reaches 95.8%, 94.5%, and 96.3%, respectively. The experimental results of this system have a specific practical significance in driver-distracted driving warnings.

Tracking the multiple Hg sources in sediments in a typical river-lake basin by isotope compositions and mixing models.

In this study, total mercury (THg) contents and Hg isotope compositions in sediments were investigated in the Lianxi River, Zijiang River and South Dongting Lake to identify and quantify multiple Hg sources and evaluate the Hg environmental processes. The THg contents, δ202Hg and Δ199Hg values in sediments were 48.22 ∼ 4284.32 µg/kg, - 1.33 ∼ 0.04‰ and - 0.25 ∼ 0.03‰, respectively. Relatively distinct Hg isotope characteristics of sediments were presented in the Lianxi River, Zijiang River and South Dongting Lake, indicating the dominant Hg sources considerably varied in these regions. Source apportionment based on MixSIAR proved that Hg in sediments mainly originated from industrial activities, and the ternary mixing model concluded non-ferrous metal smelting was the dominant industrial Hg contributor in the Lianxi River. Compared with the Lianxi River, the relative contribution of Hg in sediments from industrial activities significantly decreased, while the relative contributions of Hg from background releases significantly increased in the Zijiang River and South Dongting Lake. Nonetheless, the contribution of industrial Hg in this study area deserves more attention. These results are conducive to further manage Hg pollution.

Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment.

BACKGROUND: IFN-γ is a pleiotropic cytokine that has been shown to affect multiple cellular functions of bovine mammary epithelial cells (BMECs) including impaired milk fat synthesis and induction of malignant transformation via depletion of arginine, one of host conditionally essential amino acids. But the molecular mechanisms of these IFN-γ induced phenotypes are still unknown. METHODS: BMECs were treated with IFN-γ for 6 h, 12 h, and 24 h. The metabolomic profiling in BMECs upon IFN-γ induction were assessed using untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomic analysis. Key differentially expressed metabolites (DEMs) were quantified by targeted metabolomics. RESULTS: IFN-γ induction resulted in significant differences in the contents of metabolites. Untargeted analysis identified 221 significantly DEMs, most of which are lipids and lipid-like molecules, organic acids and derivatives, organ heterocyclic compounds and benzenoids. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEMs were enriched in fructose and mannose metabolism, phosphotransferase system (PTS), ß-alanine metabolism, arginine and proline metabolism, methane metabolism, phenylalanine metabolism, and glycolysis/gluconeogenesis. Quantification of selected key DEMs by targeted metabolomics showed significantly decreased levels of D-(-)-mannitol, argininosuccinate, and phenylacetylglycine (PAG), while increased levels in S-hydroxymethylglutathione (S-HMG) and 2,3-bisphospho-D-glyceric acid (2,3-BPG). CONCLUSIONS: These results provide insights into the metabolic alterations in BMECs upon IFN-γ induction and indicate potential theoretical basis for clarifying IFN-γ-induced diseases in mammary gland.

Mercury contamination in the water and sediments of a typical inland river - Lake basin in China: Occurrence, sources, migration and risk assessment.

In the area affected by non-ferrous metal mining activities, mercury (Hg) contamination in the water and sediments posed potential risks to ecology and human health. In this study, river water and sediment samples were collected in the Zijiang river - South Dongting Lake basin to analyze Hg residues, identify potential Hg sources and evaluate the ecological and health risks posed by Hg contamination. In this study, the average concentrations of THg, PHg, DHg and DMeHg in river water were 38.05 ± 27.13 ng/L, 25.18 ± 26.83 ng/L, 12.88 ± 9.64 ng/L and 0.29 ± 0.07 ng/L, respectively. The THg and MeHg contents in sediments were 234.24 ± 152.93 µg/kg and 0.48 ± 0.16 µg/kg, respectively. The more enrichment of Hg in sediments was observed in the Zijiang River than in the South Dongting Lake, especially in the upstream and midstream regions. Two potential Hg sources in the basin were identified by correlation matrix, principal component analysis (PCA) and positive matrix factorization (PMF) model. The comparable Hg flux with other rivers worldwide was found in the Zijiang River (0.53 Mg/y). Furthermore, it was found by the delayed geochemical hazard (DGH) model that the ecological risk of Hg was more significant in the Zijiang River with more frequent transformation pathways. For different populations, the health risk values caused by Hg were all lower than the USEPA's guideline value. This study provided sound evidence for further control of Hg contamination.

Efficient removal of Sb(III) from water using ß-FeOOH-modified biochar:Synthesis, performance and mechanism.

Since the toxicity of Sb(III) is 10 times as high as that of Sb(V) in the environment, it is urgent to find a way to cut down Sb(III). ß-FeOOH-modified biochar (ß-FeOOH/BC) was prepared and used to remove Sb(III). The characterization results suggested that oxygen-containing functional groups formed on ß-FeOOH/BC, which increased the Sb(III) removal efficiency. Even under complex water matrix conditions, the outstanding adsorption performance of ß-FeOOH/BC for Sb(III) was obtained. The adsorption reaction rapidly reached a high removal efficiency within 5 min and approached adsorption equilibrium in about 6 h. The adsorption process was fitted to pseudo-second-order kinetics. Amount of maximum adsorption was 202.53 mg g-1 at 308 K according to Langmuir model. ß-FeOOH/BC removed Sb(III) mainly through pore-filling complexation, cation-π and coordination exchange. The CO sites and persistent free radicals (PFRs) acted as electron acceptors, facilitating the electron transfer. In brief, ß-FeOOH/BC adsorbent material could adsorb and oxidize Sb(III), which showed excellent prospects for reducing the risk of Sb(III).

Efficacy of bile acid profiles in diagnosing and staging of alcoholic liver disease.

AIM: The diagnosis of alcoholic liver disease (ALD) is still a great challenge. Therefore, the purpose of this study is to identify and characterize new metabolomic biomarkers for the diagnosis and staging of ALD. METHODS: A total of 127 patients with early liver injury, 40 patients with alcoholic cirrhosis (ALC) and 40 healthy controls were included in this study. Patients with early liver injury included 45 patients with alcoholic liver disease (ALD), 40 patients with non-alcoholic fatty liver disease (NAFLD) and 40 patients with viral liver disease (VLD). The differential metabolites in serum samples were analyzed using ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry, and partial metabolites in the differential metabolic pathway were identified by liquid chromatography- tandem mass spectrometry. RESULTS: A total of 40 differential metabolites and five differential metabolic pathways in the four groups of patients with early liver disease and healthy controls were found, and the metabolic pathway of primary bile acid (BA) biosynthesis was the pathway that included the most differential metabolites. Therefore, 22 BA profiles were detected. The results revealed that the changes of BA profiles were most pronounced in patients with ALD compared with patients with NAFLD and VLD, in whom 12 differential BAs were diagnostic markers of ALD (AUC = 0.883). The 19 differential BAs in ALC and ALD were diagnostic markers of the stage of alcoholic hepatic fibrosis (AUC = 0.868). CONCLUSION: BA profiles are potential indicators in the diagnosis of ALD and evaluation of different stages.

Protective efficacy of a universal influenza mRNA vaccine against the challenge of H1 and H5 influenza A viruses in mice.

Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin (HA) glycoprotein. The immunogenic subdominant stem domain of HA is highly conserved and can be recognized by antibodies capable of binding multiple HA subtypes. Therefore, the HA stem antigen is a promising target for the design of universal influenza vaccines. On the basis of an established lipid nanoparticle-encapsulated mRNA vaccine platform, we designed and developed a novel universal influenza mRNA vaccine (mHAs) encoding the HA stem antigen of the influenza A (H1N1) virus. We tested the efficacy of the mHAs vaccine using a mouse model. The vaccine induced robust humoral and specific cellular immune responses against the stem region of HA. Importantly, two doses of the mHAs vaccine fully protected mice from lethal challenges of the heterologous H1N1 and heterosubtypic H5N8 influenza viruses. Vaccinated mice had less pathological lung damage and lower viral titers than control mice. These results suggest that an mRNA vaccine using the conserved stem region of HA may provide effective protection against seasonal and other possible influenza variants.

4'-phosphopantetheine acts as a potential antioxidant to limit atherosclerotic plaque formation by inhibiting ROS generation.

Coronary heart disease (CHD) is caused by coronary atherosclerosis and has a high morbidity and mortality rate worldwide. There are challenges in both early screening and treatment of CHD. The appearance and development of CHD is a complex metabolic disorder process. Therefore, to search for new biomarkers of CHD, we analyzed the peripheral blood metabolome in patients with CHD. In the study, a plasma metabolite, 4'-Phosphopantetheine (4-PPanSH), which was discovered by HPLC-MS/MS, as peripheral blood 4-PPanSH decreases, the degree of coronary blockage gradually aggravates. In addition, the 4-PPanSH supplement limited atherosclerotic plaque formation and endothelial injury in mice. Further, in vascular endothelial cells, 4-PPanSH effectively inhibited ROS generation and ox-LDL accumulation. In summary, 4-PPanSH was associated with the degree of coronary stenosis, and the 4-PPanSH supplement reduced atherosclerotic plaque generation, which could be associated with 4-PPanSH acting as a potent antioxidant that inhibits ROS generation and alleviates vascular endothelial injury.

Lactobacillus rhamnosus GG protects against atherosclerosis by improving ketone body synthesis.

Atherosclerosis (AS) is a major cause of death and morbidity worldwide. There is an increasing amount of evidence that the gut microbiota plays an important role in disorders associated with lipid metabolism, such as AS, and alterations in the composition of the gut microbiota and its metabolic potential have been identified as contributing factors in the development of AS. Recently, probiotics have attracted great interest for their excellent cholesterol-lowering ability, their capacity to improve vascular endothelial function, and their participation in the remodeling of the intestinal flora to prevent AS. The incidental findings of our other study suggest that probiotic Lactobacillus rhamnosus GG may be associated with slowing the progression of AS. Thus, we delivered strain GG into mice by oral feeding and found that strain GG could effectively inhibit AS plaque generation. We analyzed the differences in gut microbiota composition and the peripheral blood metabolome in mice after oral feeding of strain GG by 16S DNA sequencing and untargeted metabolomics, respectively. The results showed that strain GG changed the composition of the gut microbiota in mice fed a high-fat diet; elevated the abundance of beneficial bacteria, such as Bilophila and Alistipes, and decreased the abundance of harmful bacteria, such as Deltaproteobacteria. The results of enrichment analysis of the gut microbiota and the peripheral blood metabolome both indicated that the antiatherosclerotic effect of strain GG might be associated with the biosynthesis pathway of ketone bodies. In addition, strain GG attenuated endothelial injury and elevated peripheral blood ketone body content in mice but did not significantly affect low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) content. In conclusion, our study provides new evidence that strain GG slows the progression of AS, which may be associated with its improvement of the gut microbiome and peripheral blood metabolome, its ability to increase the abundance of beneficial bacteria, and its participation in unsaturated fatty acid and ketone body synthesis and degradation. KEY POINTS: • L. rhamnosus GG attenuated endothelial injury and atherosclerotic plaque formation • L. rhamnosus GG elevated the abundance of beneficial bacteria • L. rhamnosus GG elevated peripheral blood ketone body content in mice.

Comparison of LC-MS3 and LC-MRM Method for Quantifying Voriconazole and Its Application in Therapeutic Drug Monitoring of Human Plasma.

The TDM of voriconazole which exhibits wide inter-individual variability is indispensable for treatment in clinic. In this study, a method that high-performance liquid chromatography tandem mass spectrometry cubed (HPLC-MS3) is first built and validated to quantify voriconazole in human plasma. The system is composed of Shimadzu Exion LCTM UPLC coupled with a Qtrap 5500 mass spectrometer. The separation of voriconazole is performed on a Poroshell 120 SB-C18 column at a flow rate of 0.8 mL/min remaining 7 min for each sample. The calibration curves are linear in the concentration range of 0.25-20 µg/mL. Intra-day and inter-day accuracies and precisions are within 8.0% at three concentrations, and the recoveries and matrix effect are all within accepted limits. In terms of stability, there is no significant degradation of voriconazole under various conditions. The HPLC-MS3 and HPLC-MRM (multiple reaction monitoring) methods are compared in 42 patients with Passing-Bablok regression and Bland-Altman plots, and the results show no significant difference between the two methods. However, HPLC-MS3 has a higher S/N (signal-to-noise ratio) and response than the MRM. Finally, the HPLC-MS3 assay is successfully applied to monitor the TDM (therapeutic drug monitoring) of voriconazole in human plasma, and this verifies that the dosing guidelines for voriconazole have been well implemented in the clinic and patients have received excellent treatment.

LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells.

BACKGROUND: IFN-γ has been traditionally recognized as an inflammatory cytokine that involves in inflammation and autoimmune diseases. Previously we have shown that sustained IFN-γ induced malignant transformation of bovine mammary epithelial cells (BMECs) via arginine depletion. However, the molecular mechanism underlying this is still unknown. METHODS: In this study, the amino acids contents in BMECs were quantified by a targeted metabolomics method. The acquisition of differentially expressed genes was mined from RNA-seq dataset and analyzed bioinformatically. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) assay were performed to detect gene mRNA and protein expression levels. CCK-8 and would healing assays were used to detect cell proliferation and migration abilities, respectively. Cell cycle phase alternations were analyzed by flow cytometry. RESULTS: The targeted metabolomics analysis specifically discovered IFN-γ induced arginine depletion through accelerating arginine catabolism and inhibiting arginine anabolism in BMECs. Transcriptome analysis identified leucine aminopeptidase 3 (LAP3), which was regulated by p38 and ERK MAPKs, to downregulate arginine level through interfering with argininosuccinate synthetase (ASS1) as IFN-γ stimulated. Moreover, LAP3 also contributed to IFN-γ-induced malignant transformation of BMECs by upregulation of HDAC2 (histone deacetylase 2) expression and promotion of cell cycle proteins cyclin A1 and D1 expressions. Arginine supplementation did not affect LAP3 and HDAC2 expressions, but slowed down cell cycle process of malignant BMECs. In clinical samples of patients with breast cancer, LAP3 was confirmed to be upregulated, while ASS1 was downregulated compared with healthy control. CONCLUSIONS: These results demonstrated that LAP3 mediated IFN-γ-induced arginine depletion to malignant transformation of BMECs. Our findings provide a potential therapeutic target for breast cancer both in humans and dairy cows.