The Role of Metabolomics and Microbiology in Urinary Tract Infection.

One of the common illnesses that affect women's physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient's urine in relation to their role in supporting host health.

Preparation of Budesonide-Loaded Liposomal Nanoparticles for Pulmonary Delivery and Their Therapeutic Effect in OVA-Induced Asthma in Mice.

Purpose: Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment. Methods: BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed. Results: The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD. Conclusion: BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.

Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined. AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism. MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease. RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats. CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.

Processing methods of the pipeline crack detection signal by a balanced field electromagnetic technique based on phase characteristics.

The balanced field electromagnetic technique is an effective way of in-line inspection to detect cracks in pipelines. A signal demodulation method based on phase characteristics is proposed for the problem of interference signals generated by the sensor tilt shaking during the detection, which affects the judgment of the cracks. The method uses a reference signal whose phase is orthogonal to the signal generated by the sensor shaking to demodulate the detection signal to eliminate the shake interference. The generation principles of crack detection signals and interference signals generated by sensor shaking are analyzed, and the influence of sensor lift-off on detection is compared. A demodulation model is established based on the characteristic of that same frequency and different phases of crack and shake signals. The feasible conditions of the method are analyzed by simulation, and the phase value of the reference signal in the demodulation method is determined. The platform detection experiment and pulling tests at different speeds are carried out, respectively, to verify the effectiveness of the proposed method. The results show that there is a significant phase difference between the signals generated by the sensor shaking and the crack. For carbon steel pipelines, the signal phase of different shake angles is -4°. When the sensor structure and excitation frequency in this study are used, the reference signal phase is chosen to be 86°. The method preserves the detection signal characteristics before processing and enables the linear output responses to be obtained for different depths of cracks.

Efferocytosis and Respiratory Disease.

Cells are the smallest units that make up living organisms, which constantly undergo the processes of proliferation, differentiation, senescence and death. Dead cells need to be removed in time to maintain the homeostasis of the organism and keep it healthy. This process is called efferocytosis. If the process fails, this may cause different types of diseases. More and more evidence suggests that a faulty efferocytosis process is closely related to the pathological processes of respiratory diseases. In this review, we will first introduce the process and the related mechanisms of efferocytosis of the macrophage. Secondly, we will propose some methods that can regulate the function of efferocytosis at different stages of the process. Next, we will discuss the role of efferocytosis in different lung diseases and the related treatment approaches. Finally, we will summarize the drugs that have been applied in clinical practice that can act upon efferocytosis, in order to provide new ideas for the treatment of lung diseases.

Multi-channel frequency difference noise analysis and cancellation method for the balanced field electromagnetic pipeline inspection gauge.

The balanced field electromagnetic technique as an effective in-line inspection method for cracks in long-distance oil and gas pipelines uses the pipeline inspection gauge (PIG) as the detection tool. PIG is characterized by the employment of a large number of sensors, but as each channel uses its crystal oscillator as a signal source, it inevitably generates frequency difference noise, which affects crack detection. A method of eliminating the frequency difference noise by using same-frequency excitation is proposed to solve the problem. Combining the principle of electromagnetic field propagation with the detection signal processing process, the formation process and characteristics of the frequency difference noise are theoretically analyzed, and the specific impact of frequency difference noise on crack detection is analyzed. The method of unified clock excitation for all channels is adopted, and a same-frequency excitation system is developed. The correctness of the theoretical analysis and the validity of the proposed method are verified by platform experiments and pulling tests. The results show that the effect of the frequency difference on noise follows the whole detection process, and the smaller the frequency difference, the longer the noise period. The frequency difference noise distorts the crack signal and is of comparable magnitude to the crack signal, which tends to drown out the crack signal. The same-frequency excitation method can eliminate frequency difference noise at the source and has a high signal-to-noise ratio. The method can provide a reference for multi-channel frequency difference noise cancellation in other AC detection technologies.

Discriminative Method for Crack Detection Signals in Balanced-Field Electromagnetic Technique Based on Amplitude-Phase Composite Figure.

The balanced-field electromagnetic technique is an effective in-line inspection method for pipeline cracks. To address the problem that the interference signal generated by the tilt jitter of the sensor during the detection process affects the judgment of cracks, this paper proposes a method to differentiate the crack detection signal from the sensor jitter signal by using an amplitude-phase composite figure. The generation principle of the detection signal was analyzed by using the mutual inductance model, and the amplitude-phase composite figure was constructed by using the components of the detection signal after quadrature demodulation. The feasibility of using the phase as a signal discrimination feature was illustrated by finite element simulations, and the characteristics of the amplitude-phase composite figure were determined. The validity of the proposed method was verified experimentally. The results show that the crack detection signal and the signal generated by the sensor jitter are of the same frequency with similar waveforms and significantly different phases. The phase base value of the crack detection signal ranges from 35° to 55°, and the phase base value of the jitter signal is -4°. In terms of the characteristics of the amplitude-phase composite figure, the crack detection signal distribution is symmetrical about the origin in the first and third quadrants, and the axial crack is closer to the Y-axis than the circumferential crack; the jitter signal is distributed in the second and fourth quadrants and has a very small angle to the X-axis. In addition, the proposed method effectively weakens the observation of the phase noise region in the detection signal of the balanced-field electromagnetic technique.

Baseline Ratio of Soluble Fas/FasL Predicts Onset of Pulmonary Hypertension in Elder Patients Undergoing Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Pulmonary hypertension (PH) is one of the most common complications associated with end-stage renal disease (ESRD). Though numerous risk factors have been founded, other risk factors remain unidentified, particularly in patients undergoing maintenance hemodialysis with elder age. Soluble Fas (sFas) and its ligand FasL (sFasL) have been reported in chronic renal disease patients; however, they have not been identified in the PH patients of elder hemodialysis patients. We aimed to determine the roles of sFas/sFasL in onset of PH in elder patients undergoing maintenance hemodialysis with ESRD. Methods: Altogether, 163 patients aged 68.00 ± 10.51 years with ESRD who undergoing maintenance hemodialysis in a prospective cohort and were followed-up for a median of 5.5 years. They underwent echocardiography examinations, liver function assessments, residual renal function, and serum ion examinations, before and after dialysis. Furthermore, levels of sFas and sFasL at baseline had also been measured. We compared demographic data, echocardiographic parameters, liver function, ions, and residual renal function as well as serum sFas and sFasL between the PH and non-PH groups. These parameters were correlated with systolic pulmonary artery pressure (sPAP) using Spearman's correlation. Moreover, univariate and adjusted logistic regression analyses have also been conducted. Results: The incidence of PH in the elder dialysis patients was 39.1%. PH populations were demonstrated with significantly higher end-diastolic internal diameters of the left atrium, left ventricle, right ventricle (RV), and pulmonary artery, as well as the left ventricular posterior wall thickness (LVWP; all p < 0.05). A higher baseline serum sFas and sFasL levels have also been identified ( p < 0.001). They also showed lower fractional shortening and left ventricular ejection fraction (LVEF; p < 0.05). Following dialysis, the post-dialysis serum potassium concentration (K+) was significantly higher in the PH group ( p = 0.013). Furthermore, the adjusted regression identified that ratio of sFas/FasL (OR: 1.587, p = 0.004), RV (OR: 1.184, p = 0.014), LVPW (OR: 1.517, p = 0.007), and post-dialysis K+ (OR: 2.717, p = 0.040) was the independent risk factors for PH while LVEF (OR: 0.875, p = 0.040) protects patients from PH. Conclusion: The baseline ratio of sFas/sFasL, RV, LVPW, and post-dialysis K+ was independent risk factors for PH onset, while LVEF was a protective factor for PH.

Investigation of A Slow-Light Enhanced Near-Infrared Absorption Spectroscopic Gas Sensor, Based on Hollow-Core Photonic Band-Gap Fiber.

Generic modeling and analysis of a slow-light enhanced absorption spectroscopic gas sensor was proposed, using a mode-tuned, hollow-core, photonic band-gap fiber (HC-PBF) as an absorption gas cell. Mode characteristics of the un-infiltrated and infiltrated HC-PBF and gas absorption enhancement of the infiltrated HC-PBF were analyzed. A general rule of microfluidic parameters for targeting different gas species in the near-infrared was obtained. Ammonia (NH3) was used as an example to explore the effects of slow light on gas detection. The second harmonic (2f) signal and Allan deviation were theoretically investigated based on the derived formulations.

Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl2 group, 25 mg/kg MnCl2 group, and 50 mg/kg MnCl2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.