Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation.

Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb-compound-biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)-saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)-lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)-glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA's downstream regulators [interleukin (IL)-1ß and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG's effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

Naringenin attenuated airway cilia structural and functional injury induced by cigarette smoke extract via IL-17 and cAMP pathways.

BACKGROUND: Cigarette smoke impairs mucociliary clearance via mechanisms such as inflammatory response and oxidative injury, which in turn induces various respiratory diseases. Naringenin, a naturally occurring flavonoid in grapes and grapefruit, has exhibited pharmacological properties such as anti-inflammatory, expectorant, and antioxidant properties. However, it is still unclear whether naringenin protects airway cilia from injury caused by cigarette smoke. PURPOSE: This study aimed to investigate the effect of naringenin on cigarette smoke extract (CSE)-induced structural and functional abnormalities in airway cilia and highlight the potential regulatory mechanism. METHODS: Initially, network pharmacology was used to predict the mechanism of action of naringenin in ciliary disease. Next, HE staining, immunofluorescence, TEM, qRT-PCR, western blot, and ELISA were performed to assess the effects of naringenin on airway cilia in tracheal rings and air-liquid interface (ALI) cultures of Sprague Dawley rats after co-exposure to CSE (10% or 20%) and naringenin (0, 25, 50, 100 µM) for 24 h. Finally, transcriptomics and molecular biotechnology methods were conducted to elucidate the mechanism by which naringenin protected cilia from CSE-induced damage in ALI cultures. RESULTS: The targets of ciliary diseases regulated by naringenin were significantly enriched in inflammation and oxidative stress pathways. Also, the CSE decreased the number of cilia in the tracheal rings and ALI cultures and reduced the ciliary beat frequency (CBF). However, naringenin prevented CSE-induced cilia damage via mechanisms such as the downregulation of cilia-related genes (e.g., RFX3, DNAI1, DNAH5, IFT88) and ciliary marker proteins such as DNAI2, FOXJ1, and ß-tubulin IV, the upregulation of inflammatory factors (e.g., IL-6, IL-8, IL-13), ROS and MDA. IL-17 signaling pathway might be involved in the protective effect of naringenin on airway cilia. Additionally, the cAMP signaling pathway might also be related to the enhancement of CBF by naringenin. CONCLUSION: In this study, we first found that naringenin reduces CSE-induced structural disruption of airway cilia in part via modulation of the IL-17 signaling pathway. Furthermore, we also found that naringenin enhances CBF by activating the cAMP signaling pathway. This is the first report to reveal the beneficial effects of naringenin on airway cilia and the potential underlying mechanisms.

Discovery of cyperenoic acid as a potent and novel entry inhibitor of influenza A virus.

Influenza therapeutics with new targets and modes of action are urgently needed due to the frequent emergence of mutants resistant to currently available anti-influenza drugs. Here we report the in vitro and in vivo anti-influenza A virus activities of cyperenoic acid, a natural compound, which was isolated from a Chinese medicine Croton crassifolius Geise. Cyperenoic acid could potently suppress H1N1, H3N2 and H9N2 virus replication with IC50 values ranging from 0.12 to 15.13 µM, and showed a low cytotoxicity against MDCK cells (CC50 = 939.2 ± 60.0 µM), with selectivity index (SI) values ranging from 62 to 7823. Oral or intraperitoneal treatment of cyperenoic acid effectively protected mice against a lethal influenza virus challenge, comparable to the efficacy of Tamiflu. Additionally, cyperenoic acid also significantly reduced lung virus titers and alleviated influenza-induced acute lung injury in infected mice. Mechanism-of-action studies revealed that cyperenoic acid exhibited its anti-influenza activity during the entry stage of viral replication by inhibiting HA-mediated viral fusion. Simulation docking analyses of cyperenoic acid with the HA structures implied that cyperenoic acid binds to the stalk domain of HA in a cavity near the fusion peptide. Collectively, these results demonstrate that cyperenoic acid is a promising lead compound for the anti-influenza drug development and this research provides a useful small-molecule probe for studying the HA-mediated viral entry process.

A Novel Antimicrobial Mechanism of Azalomycin F Acting on Lipoteichoic Acid Synthase and Cell Envelope.

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against S. aureus. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on S. aureus cells, which would eventually cause the cellular autolysis.

Potential Beneficial Effects of Naringin and Naringenin on Long COVID-A Review of the Literature.

Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.

Naringenin regulates cigarette smoke extract-induced extracellular vesicles from alveolar macrophage to attenuate the mouse lung epithelial ferroptosis through activating EV miR-23a-3p/ACSL4 axis.

BACKGROUND: Alveolar macrophages are one of the momentous regulators in pulmonary inflammatory responses, which can secrete extracellular vesicles (EVs) packing miRNAs. Ferroptosis, an iron-dependent cell death, is associated with cigarette smoke-induced lung injury, and EVs have been reported to regulate ferroptosis by transporting intracellular iron. However, the regulatory mechanism of alveolar macrophage-derived EVs has not been clearly illuminated in smoking-related pulmonary ferroptosis. Despite the known anti-ferroptosis effects of naringenin in lung injury, whether naringenin controls EVs-mediated ferroptosis has not yet been explored. PURPOSE: We explore the effects of EVs from cigarette smoke-stimulated alveolar macrophages in lung epithelial ferroptosis, and elucidate the EV miRNA-mediated pharmacological mechanism of naringenin. STUDY DESIGN AND METHODS: Differential and ultracentrifugation were conducted to extract EVs from different alveolar macrophages treatment groups in vitro. Both intratracheal instilled mice and treated epithelial cells were used to investigate the roles of EVs from alveolar macrophages involved in ferroptosis. Small RNA sequencing analysis was performed to distinguish altered miRNAs in EVs. The ferroptotic effects of EV miRNAs were examined by applying dual-Luciferase reporter assay and miRNA inhibitor transfection experiment. RESULTS: Here, we firstly reported that EVs from cigarette smoke extract-induced alveolar macrophages (CSE-EVs) provoked pulmonary epithelial ferroptosis. The ferroptosis inhibitor ferrostatin-1 treatment reversed these changes in vitro. Moreover, EVs from naringenin and CSE co-treated alveolar macrophages (CSE+Naringenin-EVs) markedly attenuated the lung epithelial ferroptosis compared with CSE-EVs. Notably, we identified miR-23a-3p as the most dramatically changed miRNA among Normal-EVs, CSE-EVs, and CSE+Naringenin-EVs. Further experimental investigation showed that ACSL4, a pro-ferroptotic gene leading to lipid peroxidation, was negatively regulated by miR-23a-3p. The inhibition of miR-23a-3p diminished the efficacy of CSE+Naringenin-EVs. CONCLUSION: Our findings firstly provided evidence that naringenin elevated the EV miR-23a-3p level from CSE-induced alveolar macrophages, thereby inhibiting the mouse lung epithelial ferroptosis via targeting ACSL4, and further complemented the mechanism of cigarette-induced lung injury and the protection of naringenin in a paracrine manner. The administration of miR-23a-3p-enriched EVs has the potential to ameliorate pulmonary ferroptosis.

Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations.

Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs.

The dynamics of Mycobacterium tuberculosis phagosome and the fate of infection.

Phagosomes are vesicles produced by phagocytosis of phagocytes, which are crucial in immunity against Mycobacterium tuberculosis (Mtb) infection. After the phagocyte ingests the pathogen, it activates the phagosomes to recruit a series of components and process proteins, to phagocytose, degrade and kill Mtb. Meanwhile, Mtb can resist acid and oxidative stress, block phagosome maturation, and manipulate host immune response. The interaction between Mtb and phagocytes leads to the outcome of infection. The dynamic of this process can affect the cell fate. This article mainly reviews the development and maturation of phagosomes, as well as the dynamics and modifications of Mtb effectors and phagosomes components, and new diagnostic and therapeutic markers involved in phagosomes.

Hypericum japonicum extract inhibited porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) infection causes lethal watery diarrhea and high mortality in neonatal piglets, leading to huge economic losses in the global swine industry. Currently, the existing commercial vaccines cannot fully control PEDV, so it is urgent to develop effective antiviral agents to complement vaccine therapy. In the present study, we investigated the antiviral effect of Hypericum japonicum extract (HJ) against PEDV in vivo and in vitro. In in vitro assays, HJ could directly inactivate PEDV strains; moreover, it inhibited the proliferation of PEDV strains in Vero or IPI-FX cells at its non-cytotoxic concentrations. Time of addition assays revealed that HJ mainly inhibited PEDV at the later stages of the viral life cycle. In in vivo, compared with the model group, HJ could reduce the viral titers in the intestines of infected piglets, and improve their intestinal pathological, indicating that HJ could protect the newborn piglets from highly pathogenic PEDV variant infection. Furthermore, this effect may be related to the fact that HJ can not only directly inhibit viruses, but also regulate the structure of intestinal microbiota. In conclusion, our results indicate that Hypericum japonicum could inhibit PEDV replication in vitro and in vivo and might possess the potential to develop as the anti-PEDV drug.

Naringenin attenuates inflammation, apoptosis, and ferroptosis in silver nanoparticle-induced lung injury through a mechanism associated with Nrf2/HO-1 axis: In vitro and in vivo studies.

With the wide application of silver nanoparticles (AgNPs), their potential damage to human health needs to be investigated. Lung is one of the main target organs after inhalation of AgNPs. Naringenin has been reported to have anti-inflammatory and anti-oxidative properties. This study aims to evaluate the protective effects of naringenin against AgNPs-induced lung injury and determine the underlying mechanism. In in vivo experiments, AgNPs were intratracheally instilled into ICR mice (l mg/kg) to establish a lung injury model. These mice were then treated with naringenin by oral gavage (25, 50, 100 mg/kg) for three days. Naringenin treatment decreased the levels of white blood cells, neutrophils, and lymphocytes in the blood, ameliorated lung injury, suppressed the release of pro-inflammatory cytokines, normalized ferroptotic markers and prevented oxidative stress with elevating Nrf2 and HO-1 protein expressions in lung. In in vitro experiments, BEAS-2B cells were firstly treated with AgNPs (320 µg/mL) and then naringenin (25, 50, and 100 µM), respectively. Naringenin attenuated AgNPs-induced oxidative stress and inflammatory response. Moreover, naringenin attenuated AgNPs-induced apoptosis with modulated low BAX, CytC, cleaved Caspase9, cleaved Caspase3 but high Bcl2. Furthermore, naringenin effectively decreased ferroptotic markers and increased the protein expressions of Nrf2 and HO-1, as well as increased the nuclear translocation of Nrf2. Importantly, the anti-apoptotic and anti-ferroptotic effects of naringenin in BEAS-2B cells were found to be at least partially Nrf2-dependent. These results indicated that naringenin exerted anti-inflammation, anti-apoptosis, and anti-ferroptosis effects and protected against AgNPs-induced lung injury at least partly via activating Nrf2/HO-1 signaling pathway.

Naringenin suppresses BEAS-2B-derived extracellular vesicular cargoes disorder caused by cigarette smoke extract thereby inhibiting M1 macrophage polarization.

Extracellular vesicles (EVs)-mediated epithelium-macrophage crosstalk has been proved to maintain lung homeostasis in cigarette smoke-induced lung diseases such as chronic obstructive pulmonary disease (COPD). In our previous study, we found that EVs derived from cigarette smoke extract (CSE) treated BEAS-2B promoted M1 macrophage polarization, which probably accelerated the development of inflammatory responses. Naringenin has been proved to suppress M1 macrophage polarization, but whether naringenin regulates macrophage polarization mediated by EVs has not been reported. In this study, we firstly found that EVs derived from naringenin and CSE co-treated BEAS-2B significantly inhibited the expression of CD86 and CD80 and the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, inducible nitric oxide synthase (iNOS), and IL-12 in macrophage induced by EVs derived from CSE-treated BEAS-2B. Further research revealed that naringenin downregulated BEAS-2B-derived EVs miR-21-3p which targeted phosphatase and tensin homolog deleted on chromosome ten/protein kinase B (PTEN/AKT) cascade in macrophages and then suppressed M1 macrophage polarization. Subsequent proteomics suggested that naringenin decreased BEAS-2B-derived EVs poly ADP-ribose polymerase (PARP)1 expression thereby suppressing M1 macrophage polarization probably. Our study provides novel pharmacological references for the mechanism of naringenin in the treatment of cigarette smoke-induced lung inflammatory diseases.

Multi-Omics Analysis Reveals the Systematic Relationship Between Oral Homeostasis and Chronic Sleep Deprivation in Rats.

Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1ß, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.

Platycladus orientalis seed extract as a potential triple reuptake MAO inhibitor rescue depression phenotype through restoring monoamine neurotransmitters.

ETHNOPHARMACOLOGY RELEVANCE: Platycladus orientalis seeds are recorded in traditional Chinese medicine (TCM) formulations for modulation of mood and physical activity in "Shen Nong Ben Cao Jing" and "Compendium of Materia Medica" and so on. Recently, we identified its extracting components and looked for the potentials in treatment for depression by improving the function of monoamine neurotransmitters. AIM OF THE STUDY: We investigated the mechanism of action of the seed extracts of P. orientalis (S4) to rescue depressive behavior in a chronic, unpredicted, mild stress (CUMS)-induced model in rats. MATERIALS AND METHODS: We used ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry to analyze the chemical constituents in S4. An assay platform in zebrafish and molecular docking were used to analyze if S4 regulated rest/wake behavior and predict the biological targets which correlated with monoamine neurotransmitters. Depressive-behavior tests (body weight, sucrose preference test, tail-suspension test, forced-swimming test) were carried in the CUMS model. After behavior tests and killing, rat brains were separated into the hippocampus, frontier cortex and dorsal raphe nucleus. The main monoamine neurotransmitters and their metabolite concentrations in these three brain regions were measured by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry. RESULTS: Forty-one compounds were identified in S4, including fatty acids, terpenoids, amino acids, plant sterols and flavonoids. S4 could increase the total rest time and decrease the waking activity of zebrafish. S4 showed high correlation with adrenaline agonists, 5-hydroxytryptamine (5-HT) reuptake inhibitors and dopamine agonists. CUMS-group rats, compared with controls, had significantly decreased body weight and preference for sucrose water, whereas the immobility time in the tail-suspension test and forced-swimming test was increased. S4 could significantly rescue the increased levels of 5-HT, noradrenaline and dopamine in the prefrontal cortex and dorsal raphe nucleus. CONCLUSIONS: We demonstrated that S4 was a potential inhibitor of MAO reuptake that could rescue depression in a CUMS-model rats by restoring monoamine neurotransmitters in different encephalic regions.

Stick-slip vibration characteristics of drilling tool during drilling in coal seam with gangue.

Aiming at the problem of stick-slip vibration caused by sudden drilling resistance torque during drilling in coal seam with gangue, the drilling tool dynamic model with two degree of freedom was established based on the interaction between the bit cutting teeth and the coal seam with gangue. So, the motion differential equation of torsional vibration of drilling tool was derived, and the torsional vibration response of drilling tool was analyzed. Taking the drilling tool with drilling depth of 300 m as an example, the response laws of angular displacement, angular velocity, resistance torque, driving torque, relative motion phase trajectory and torsional vibration of the drill bit were discussed. The results show that the drilling tool has obvious stick-slip vibration under the action of sudden drilling resistance in the process of drilling in coal seam with gangue. The angular velocity of the drill bit moves alternately between the viscous stage and the sliding stage. A stable limit cycle will appear in the phase trajectory curve of the drill bit.

Association of TyG Index with CT Features in Patients with Tuberculosis and Diabetes Mellitus.

BACKGROUND: The purpose of this study was to investigate the association of the triglyceride glucose (TyG) index, a surrogate marker of insulin resistance (IR) with a high sensitivity of 96.5% and a specificity of 85.0% for the diagnosis of IR, with computed tomography (CT) features in patients with tuberculosis and diabetes mellitus. METHODS: A total of 247 subjects were enrolled from July, 2020 to May, 2021. The basic clinical features and CT features were analyzed. In addition, multivariate logistic regression analysis models were employed to evaluate the association of the TyG indicator with CT features in participants. RESULTS: In the quartile groups of TyG index, air bronchial sign detection rate was 11.7%, 14.5%, 23.2%, and 44.1%; large segmented leafy shadow detection rate was 27.9%, 40.6%, 46.4%, and 66.2%; thick-walled cavity was found in 38.2%, 43.4%, 57.9%, and 69.1%; the rate of multiple cavities was 17.6%, 27.5%, 36.2%, 52.9%; the rate of lymph node enlargement was 22.1%, 17.4%, 28.9%, and 38.2%, respectively. In addition, the positive relation with the TyG index and the prevalence of abnormal CT signs was observed in the fully adjusted model: TyG, per one-unit increase: air bronchial sign: adjusted odds ratio (AOR) 3.92, 95% CI 1-15.35, P = 0.049; multiple cavities: AOR 4.1, 95% CI 1.26-13.31, P = 0.019; thick-walled cavity: AOR 2.89, 95% CI 1.05-8.03, P = 0.041. In quartile of TyG index, compared with patients in quartile 1, the AOR (95% CI) values for air bronchial sign in quartile 4 was 8.1 (1.7-44), p = 0.011; multiple cavities was 7.1 (1.7-32), p = 0.008; thick-walled cavity was 7.8 (1.9-34.7), p = 0.005. CONCLUSION: The present study showed that an increased TyG index was positively related to the severity of patients with T2DM-PTB.

Tensile Properties and Fracture Mechanism of Thermal Spraying Polyurea.

In this study, polyurea was experimentally tested under various spraying temperatures and pressures. The number of holes and the pore size produced after the tensile fracture of the polyurea were counted to illustrate the effect of the various spraying temperatures and pressures on the performance of the polyurea. The tensile characteristics of polyurea were greatly influenced by the spraying temperatures and pressures, according to the experimental findings and statistical analysis. The polyurea tensile performance was best when the spraying pressure was 17.25 MPa with a spraying temperature of 70 °C. The fracture mechanism was illustrated by the silver streaking phenomenon generated during the tensile stretching process. The fracture energy was absorbed by the fracture holes and pores during silver streaking, thus creating the huge gap in tensile properties.

Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats.

As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in biological samples, in vitro, were determined using a validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method, and, in vivo, samples were assayed by an ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method. Based on these methods, the pharmacokinetics of azalomycin F were first investigated. Its plasma concentration-time courses and pharmacokinetic parameters in rats were obtained by a non-compartment model for oral (26.4 mg/kg) and intravenous (2.2 mg/kg) administrations. The results indicate that the oral absolute bioavailability of azalomycin F is very low (2.39 ± 1.28%). From combinational analyses of these pharmacokinetic parameters, and of the results of the in-vitro absorption and metabolism experiments, we conclude that azalomycin F is absorbed relatively slowly and with difficulty by the intestinal tract, and subsequently can be rapidly distributed into the tissues and/or intracellular f of rats. Azalomycin F is stable in plasma, whole blood, and the liver, and presents plasma protein binding ratios of more than 90%. Moreover, one of the major elimination routes of azalomycin F is its excretion through bile and feces. Together, the above indicate that azalomycin F is suitable for administration by intravenous injection when used for systemic diseases, while, by oral administration, it can be used in the treatment of diseases of the gastrointestinal tract.

miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization.

Inhalation of cigarette smoke induces airway and parenchyma inflammation that predisposes smokers to multiple lung diseases such as COPD. Macrophage polarization, an important specifying feature of inflammation, is involved in the progression of pulmonary inflammation. Exosomes and their loaded miRNAs provide a medium for cross-talk between alveolar macrophages and lung epithelial cells to maintain lung homeostasis. In this study, we treated Beas-2B with CSE to speculate the effects of Beas-2B-derived exosomes on macrophage polarization and performed exosomal miRNAomics analysis to explore the mechanism. We found that CSE-treated Beas-2B-derived exosomes could not only increase the percentages of CD86+, CD80+ CD163+, and CD206+ cells but also induce the secretion of TNF-α, IL-6, iNOS, IL-10, Arg-1, and TGF-ß, indicating both M1 and M2 polarization of RAW264.7 macrophages were promoting. We performed miRNAomics analysis to identify 27 differentially expressed exosomal miRNAs such as miR-29a-3p and miR-1307-5p. Next, we obtained 14942 target genes of these miRNAs such as SCN1A and PLEKHA1 through the prediction of TargetScan and miRanda. We utilized KEGG enrichment analysis for these targets to identify potential pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway on the regulation of macrophage polarization. We further found that miR-21-3p or miR-27b-3p may play critical roles in the promotion of CSE-Exo on macrophage polarization by miRNA interference. Collectively, this study provided novel information for diagnostic and therapeutic tactics of cigarette smoke-related lung diseases.

Fertility and early embryonic development toxicity assessment of naringin in Sprague-Dawley rats.

Naringin is a dihydroflavonoid abundantly existed in grapefruit and related citrus species. The double directional adjusting function of estrogenic and anti-estrogenic activities of naringin and its aglycone naringenin has raised concern about possible risks of unwanted interference with endocrine regulation. Herein we assessed the safety of naringin on fertility and early embryonic development toxicity in Sprague-Dawley rats. Twenty-two male and 22 female rats per group were orally given naringin at 0, 50, 250, and 1250 mg/kg/day. Male rats were administered beginning 9 weeks prior to mating and continued until necropsy. Dosing to female began 2 weeks before mating and continued until gestation day 7. There were no obvious effects of naringin on physical signs, animal behavior, and survival rate, although female and male rats from 1250 mg/kg group had lower body weight and tended to have less food consumption. Importantly, no treatment-related effects of naringin were found in relation to fertility and early embryonic development. Under these experimental conditions, it was concluded that the no-observed-adverse-effect levels (NOAEL) of naringin were at least 1250 mg/kg/day for fertility and early embryonic development in rats.

The Effects of Naringenin on miRNA-mRNA Profiles in HepaRG Cells.

Naringenin, a natural flavonoid widely found in citrus fruits, has been reported to possess anti-oxidant, anti-inflammatory, and hepatoprotective properties as a natural dietary supplement. However, the regulatory mechanism of naringenin in human liver remains unclear. In the present study, messenger RNA sequencing (mRNA-seq), microRNA sequencing (miRNA-seq), and real-time qPCR were used to distinguish the expression differences between control and naringenin-treated HepaRG cells. We obtained 1037 differentially expressed mRNAs and 234 miRNAs. According to the target prediction and integration analysis in silico, we found 20 potential miRNA-mRNA pairs involved in liver metabolism. This study is the first to provide a perspective of miRNA-mRNA interactions in the regulation of naringenin via an integrated analysis of mRNA-seq and miRNA-seq in HepaRG cells, which further characterizes the nutraceutical value of naringenin as a food additive.