Early-life antibiotic exposure promotes house dust mite-induced allergic airway inflammation by impacting gut microbiota and lung lipid metabolism.

Asthma is a chronic inflammatory respiratory disease. Early-life antibiotic exposure is a unique risk factor for the incidence and severity of asthma later in life. Perturbations in microbial-metabolite-immune interaction caused by antibiotics are closely associated with the pathogenesis of allergy and asthma. We investigated the effect of early intervention with common oral antibiotics on later asthma exacerbations and found that different antibiotic exposures can amplify different types of immune responses induced by HDM. Cefixime (CFX) promoted a biased type 2 inflammation, azithromycin (AZM) enhanced Th17 immune response, and cefuroxime axetil (CFA) induced eosinophils recruitment. Moreover, early-life antibiotic exposure can have short- and long-term effects on the abundance, composition, and diversity of the gut microbiota. In the model of CFX-promoted type 2 airway inflammation, fecal metabolomics indicated abnormal lipid metabolism and T cell response. Lipidomic also suggested allergic airway inflammation amplified by CFX is closely associated with abnormal lipid metabolism in lung tissues. Moreover, abnormalities in lipid metabolism-related genes (LMRGs) were found to have cellular heterogeneity be associated with asthma severity by bioinformatics analysis.

Acoustic emission characteristic of sandstone and sandstone like material under multi-path loading.

Using spline interpolation to select proportions of similar materials, a comparative analysis of the fracturing behavior of sandstone specimens and similar material specimens was conducted through Brazilian splitting tests under multi-path loading. The study revealed that during stepwise loading, both sandstone and similar materials exhibited memory effects and plastic deformation. However, under constant velocity loading, the relationship between force and displacement in sandstone showed linearity after compaction. Employing MATLAB optimization algorithms for the inversion of acoustic emission event information, the distribution of fracture points, and the evolution of cracks were analyzed. The findings indicated that under stepwise loading, both sandstone and similar materials exhibited banded distribution of peak frequencies, with sandstone concentrated in the mid-low-frequency range and similar materials leaning towards the low-frequency range. The amplitude-frequency characteristics of acoustic emission signals suggested that initially, sandstone produced low-frequency, low-amplitude signals. As cracks developed, these signals gradually transformed into high-frequency, high-amplitude signals, ultimately leading to macroscopic failure. The ringing counts and b-values of sandstone displayed an approximate "W" shape distribution, with a subsequent decrease in b-values during final failure. In contrast, the acoustic emission counts were inversely related to b-values. Similar materials exhibited slightly more acoustic emission counts than sandstone, with relatively lower b-values. The crack development process of both sandstone and similar materials was confirmed through these observations. From the perspective of section initiation and local damage, sandstone and similar materials exhibited similar failure characteristics. The proportions of quartz sand: cement: water = 9:1:0.9 in similar materials demonstrated the most similar characteristics to sandstone in terms of mechanical loading, acoustic emission features, and failure morphology. This suggests that these similar materials can be used as substitutes for sandstone in analogous simulation experiments. The study provides theoretical support for understanding rock fracture mechanisms, offers guidance for the selection and proportioning of similar materials, and holds significance for predicting and controlling rock fracture behavior in engineering applications.

Triptolide attenuates CCL4-induced liver fibrosis by regulating the differentiation of CD4+ T cells in mice.

Liver fibrosis is a major global health issue, and immune dysregulation is a main contributor. Triptolide is a natural immunosuppressive agent with demonstrated effectiveness in ameliorating liver fibrosis, but whether it exerts anti-liver fibrotic effects via immunoregulation remains obscure. In this study, first, by employing a CCL4-induced liver fibrosis mouse model, we demonstrated that triptolide could alleviate pathological damage to liver tissue and attenuate liver function damaged by CCL4. In addition, triptolide inhibited the expression of liver fibrotic markers such as hydroxyproline, collagen type IV, hyaluronidase, laminin, and procollagen type III, and the protein expression of α-SMA in CCL4-induced liver fibrosis. Second, with the help of network pharmacology, we predicted that triptolide's anti-liver fibrotic effects might occur through the regulation of Th17, Th1, and Th2 cell differentiation, which indicated that triptolide might mitigate liver fibrosis via immunoregulation. Finally, multiplex immunoassays and flow cytometry were adopted to verify this prediction. The results suggested that triptolide could reverse the aberrant expression of inflammatory cytokines caused by CCL4 and regulate the differentiation of Th1, Th2, Th17, and Treg cells. In conclusion, triptolide could attenuate CCL4-induced liver fibrosis by regulating the differentiation of CD4+ T cells. The results obtained in this study extended the application of triptolide and introduced a new mechanism of triptolide's anti-liver fibrotic effects.

Friend or foe? The dual role of triptolide in the liver, kidney, and heart.

Triptolide, a controversial natural compound due to its significant pharmacological activities and multiorgan toxicity, has gained much attention since it was isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, in addition to its severe toxicity, triptolide also presents powerful therapeutic potency in the same organs, such as the liver, kidney, and heart, which corresponds to the Chinese medicine theory of You Gu Wu Yun (anti-fire with fire) and deeply interested us. To determine the possible mechanisms involved in the dual role of triptolide, we reviewed related articles about the application of triptolide in both physiological and pathological conditions. Inflammation and oxidative stress are the two main ways triptolide exerts different roles, and the cross-talk between NF-κB and Nrf2 may be one of the mechanisms responsible for the dual role of triptolide and may represent the scientific connotation of You Gu Wu Yun. For the first time, we present a review of the dual role of triptolide in the same organ and propose the possible scientific connotation of the Chinese medicine theory of You Gu Wu Yun, hoping to promote the safe and efficient use of triptolide and other controversial medicines.

Proteomic Analysis of Human Follicular Fluid Reveals the Pharmacological Mechanisms of the Chinese Patent Drug Kunling Pill for Improving Diminished Ovarian Reserve.

Objective: To explore the pharmacological mechanism of a Chinese patent drug (Kunling Pill (KLP)) on improving diminished ovarian reserve based on proteomic analysis. Methods: A total of 18 patients divided into three groups (the normal ovary reserve (NOR), diminished ovary reserve (DOR), and KLP groups) undergoing assisted reproductive technology by standard ovarian stimulation protocols were recruited to collect follicular fluid. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins by nano-LC-MS/MS. Bioinformatic analysis was conducted to predict the functions and pathways of the identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in the three groups. Results: A total of 144 differentially expressed proteins were screened out, including 56 proteins that were downregulated and 88 proteins that were upregulated in the DOR group compared with the NOR group, while 27 proteins were shared in the KLP-treated group. Among them, 10 proteins were upregulated and 17 proteins were downregulated in the KLP-treated group compared with the DOR group. The most enriched biological processes accounted for 28 GO terms, including cellular process, biological regulation, metabolic process, and regulation of biological process. Significant pathways were associated with fatty acid elongation, fatty acid degradation, fatty acid metabolism, nicotinate and nicotinamide metabolism, and valine, leucine, and isoleucine degradation. Conclusion: Our study provides the proteome profiles of human follicular fluid from DOR patients treated by KLP. Functional analyses of proteome datasets revealed that core proteins (SAA1, MIF, and PRDX5) and related pathways (fatty acid metabolism, nicotinate and nicotinamide metabolism, and tyrosine and purine metabolism) are possible pharmacological mechanisms through which KLP improves DOR. Therefore, these findings may help better understand the complex mechanisms through which DOR is treated by the Chinese patent drug KLP.

MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12.

OBJECTIVE: To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. METHODS: The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. RESULTS: MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. CONCLUSION: MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.

Postsynthetic functionalization of water stable zirconium metal organic frameworks for high performance copper removal.

In this work, a water stable zirconium metal-organic framework functionalized with thiol groups was synthesized by a solvent-assisted ligand incorporation technique. The composites were characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, specific surface area measurement and field emission scanning electron microscopy. The prepared material was then used as a novel adsorbent for Cu(ii) removal from water. The experimental parameters associated with adsorption capability, such as the initial solution pH, contact time, and the presence of competing cations were investigated in detail. Under the optimal conditions, the adsorption follows a pseudo-second-order kinetics, and the equilibration time for the adsorption is 15 min. The Langmuir adsorption model was in better correlation with the isothermal adsorption data than the Freundlich model. The maximum Cu(ii) adsorption capacity reached up to 42.70 mg g-1. Quantitative recovery of Cu(ii) was achieved by using 0.1 mol L-1 HCl. The prepared adsorbent has fast adsorption efficiency, high adsorption capacity, and exceptional stability up to 50 adsorption/desorption cycles. It can be used as a promising candidate material for heavy metal ion removal and water treatment.