Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Integrated Transcriptome and Proteome Analyses of ß-Conglycinin-Induced Intestinal Damage in Piglets.

ß-conglycinin (ß-CG) induces intestinal damage in piglets; however, its regulatory mechanisms are not fully understood. This study aimed to investigate the molecular mechanisms by which ß-CG regulates intestinal injury in piglets through downstream genes and proteins. Our findings revealed that ß-CG significantly reduced villus height while increasing the crypt depth. In addition, we analyzed the transcriptome and proteome of jejunum tissues after the ß-CG treatment. In total, 382 differentially expressed genes (DEGs) and 292 differentially expressed proteins (DEPs) were identified between the treatment and the control groups. The expression levels of DEGs and DEPs were validated by using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting, respectively. The findings revealed a consistent correlation between their expression levels and transcriptomic and proteomic data. In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs and DEPs revealed their enrichment in oxidation-related GOs, as well as in lysosome-related pathways. A protein-protein interaction (PPI) regulatory network was constructed based on the DEPs. The integration of transcriptomic and proteomic analyses identified six genes that were significantly different at both the transcript and the protein levels. This study provides valuable insights into the molecular mechanisms underlying ß-CG-induced intestinal injury in piglets.

Steric trapping strategy for studying the folding of helical membrane proteins.

Elucidating the folding energy landscape of membrane proteins is essential to the understanding of the proteins' stabilizing forces, folding mechanisms, biogenesis, and quality control. This is not a trivial task because the reversible control of folding is inherently difficult in a lipid bilayer environment. Recently, novel methods have been developed, each of which has a unique strength in investigating specific aspects of membrane protein folding. Among such methods, steric trapping is a versatile strategy allowing a reversible control of membrane protein folding with minimal perturbation of native protein-water and protein-lipid interactions. In a nutshell, steric trapping exploits the coupling of spontaneous denaturation of a doubly biotinylated protein to the simultaneous binding of bulky monovalent streptavidin molecules. This strategy has been evolved to investigate key elements of membrane protein folding such as thermodynamic stability, spontaneous denaturation rates, conformational features of the denatured states, and cooperativity of stabilizing interactions. In this review, we describe the critical methodological advancement, limitation, and outlook of the steric trapping strategy.

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis.

BACKGROUND: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. METHODS: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. RESULTS: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. CONCLUSIONS: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

Competitive and synergic evolution of the water-food-ecology system: A case study of the Beijing-Tianjin-Hebei region, China.

A vital approach to attaining sustainable development lies in the in-depth examination of both competition and synergy between these subsystems from a water-food-ecology (WFE) system perspective, while previous or existing studies have limitations in to quantitative characterize and evaluation the cooperative and competitive relationships between different systems. In this study, an evaluation indicator system is constructed from the two dimensions of resources and efficiency, and the WFE synergic development capacity (WFE-SDC) is proposed by integrating the order degree of the coupled system, enables a multidimensional and comprehensive quantitative assessment of the sustainable development of the WFE system. Then a synergic evolution model is constructed to explore the competitive and synergic evolution of the WFE system in the Beijing-Tianjin-Hebei region. The following key insights were obtained: (1) The WFE-SDC (range of 0-1) shows a fluctuating increase, indicating a shift from mild dysfunctional recession to intermediate synergic development (0.24 to 0.72). (2) Principal factors impeding WFE-SDC encompass diversion water, ecology water consumption, grain demand, reclaimed water consumption, and outbound water, both come from resource dimension, with a combined impediment degree of over 46 %, and the improvement of efficiency dimension may improve the WFE-SDC. (3) The water subsystem acts as a driving force for synergic development, fostering cooperation within the food and ecology subsystems, although they mainly operate in a competitive state. (4) Within the WFE system, Beijing, Tianjin, and Hebei exhibited mutual cooperation and significantly contributed to one another's development. Beijing has played a pivotal role in the progress of both Tianjin and Hebei. This study offers valuable insights for the formulation of policies and the application of technical approaches for the sustainable development of the WFE system in relevant regions.

Mesenchymal stem cells inhibit ferroptosis by activating the Nrf2 antioxidation pathway in severe acute pancreatitis-associated acute lung injury.

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) remains a significant challenge for healthcare practitioners because of its high morbidity and mortality; therefore, there is an urgent need for an effective treatment. Mesenchymal stem cells (MSCs) have shown significant potential in the treatment of a variety of refractory diseases, including lung diseases. This study aimed to investigate the protective effects of MSCs against SAP-ALI and its underlying mechanisms. Our results suggest that MSCs mitigate pathological injury, hemorrhage, edema, inflammatory response in lung tissue, and lipopolysaccharide (LPS)-induced cell damage in RLE-6TN cells (a rat alveolar epithelial cell line). The results also showed that MSCs, similar to the effects of ferrostatin-1 (ferroptosis inhibitor), suppressed the ferroptosis response, which was manifested as down-regulated Fe2+, malondialdehyde, and reactive oxygen species (ROS) levels, and up-regulated glutathione peroxidase 4 (GPX4) and glutathione (GSH) levels in vivo and in vitro. The activation of ferroptosis by erastin (a ferroptosis agonist) reversed the protective effect of MSCs against SAP-ALI. Furthermore, MSCs activated the nuclear factor erythroid 2 associated factor 2 (Nrf2) transcription factor, and blocking the Nrf2 signaling pathway with ML385 abolished the inhibitory effect of MSCs on ferroptosis in vitro. Collectively, these results suggest that MSCs have therapeutic effects against SAP-ALI. The specific mechanism involves inhibition of ferroptosis by activating the Nrf2 transcription factor.

Enhancing La(III) biosorption and biomineralization with Micromonospora saelicesensis: Involvement of phosphorus and formation of monazite nano-minerals.

The release of rare earth elements (REEs) from mining wastes and their applications has significant environmental implications, necessitating the development of effective prevention and reclamation strategies. The mobility of REEs in groundwater due to microorganisms has garnered considerable attention. In this study, a La(III) resistant actinobacterium, Micromonospora saelicesensis KLBMP 9669, was isolated from REE enrichment soil in GuiZhou, China, and evaluated for its ability to adsorb and biomineralize La(III). The findings demonstrated that M. saelicesensis KLBMP 9669 immobilized La(III) through the physical and chemical interactions, with immobilization being influenced by the initial La(III) concentration, biomass, and pH. The adsorption kinetics followed a pseudo-second-order rate model, and the adsorption isotherm conformed to the Langmuir model. La(III) adsorption capacity of this strain was 90 mg/g, and removal rate was 94 %. Scanning electron microscope (SEM) coupled with energy dispersive X-ray spectrometer (EDS) analysis revealed the coexistence of La(III) with C, N, O, and P. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) investigations further indicated that carboxyl, amino, carbonyl, and phosphate groups on the mycelial surface may participate in lanthanum adsorption. Transmission electron microscopy (TEM) revealed that La(III) accumulation throughout the M. saelicesensis KLBMP 9669, with some granular deposits on the mycelial surface. Selected area electron diffraction (SAED) confirmed the presence of LaPO4 crystals on the M. saelicesensis KLBMP 9669 biomass after a prolonged period of La(III) accumulation. This post-sorption nano-crystallization on the M. saelicesensis KLBMP 9669 mycelial surface is expected to play a crucial role in limiting the bioimmobilization of REEs in geological repositories.

Expression of serum inflammatory cytokines and oxidative stress markers and their correlation with coronary artery calcium score in patients with coronary heart disease.

Introduction: The present study was conducted to explore the expression of serum inflammatory cytokines and oxidative stress markers in patients with coronary heart disease (CHD), with an attempt to analyze their relationship with the coronary artery calcium score (CACS) by coronary computed tomography angiography (CCTA). Material and methods: It total 81 patients with coronary heart disease and 81 healthy adults were included as the observation group and the control group, respectively. The levels of serum interleukin (IL)-6 and IL-12 of the two groups were detected by ELISA, and serum superoxide dismutase (SOD) was detected by the hydroxylamine oxidation method. Micro-RNA-497-5p (miR-497-5p) was screened out as a possible new CHD biomarker and its serum level was measured by real-time fluorescence quantitative PCR. The CACS of patients in the observation group was calculated by the Agatston method to analyze the correlation between the abovementioned indexes and CACS. Results: With increase in the number of CHD lesions, the levels of IL-6, IL-12 and miR-497-5p rose gradually while the level of SOD decreased gradually. In the observation group, IL-6, IL-12 and miR-497-5p were positively correlated with CACS while SOD was negatively correlated with CACS. Conclusions: Abnormal expression levels of serum IL-6, IL-12, SOD and miR-497-5p may be able to reveal the severity of the disease, and the combination with CACS is of potential value in terms of evaluating the condition of patients harboring coronary heart disease.

Tissue Identification of Intervertebral Disc Anatomy Using Forward-oriented Ultrasound Endoscopic System: A Feasibility Study.

Minimally invasive surgery is widely used for spine surgery, however the commonly used optical endoscopes cannot identity tissues under surface. In this study, a forward-oriented ultrasound endoscopic system was proposed to detect and identity different types of tissues for surgical approaches. A total of 150 ultrasound image data were collected from 6 types of intervertebral disc tissue using a custom-developed endoscopic probe. The gray-level co-occurrence matrix (GLCM) properties including energy (angular second moment, ASM), contrast, entropy, and homogeneity (inverse difference moment, IDM) were calculated on the acquired ultrasound images, and the single-parameter and combined parameter were applied for tissue classification. The classification accuracies of fibrous ring, nerve roots and bone were 100%, and the overall accuracy for all tissues was 73.33%. The results indicated that the combined parameter method provided more accurate classification output. It demonstrated that the proposed endoscopic ultrasonography system had the potential of identifying different tissues under surface during the endoscopic spine surgery.Clinical Relevance-This study establishes that the forward-oriented ultrasound endoscopic system was feasible to identify different types of tissues under surface during the endoscopic spine surgery.

Optimization of small molecule degraders and antagonists for targeting estrogen receptor based on breast cancer: current status and future.

The estrogen receptor (ER) is a classical receptor protein that plays a crucial role in mediating multiple signaling pathways in various target organs. It has been shown that ER-targeting therapies inhibit breast cancer cell proliferation, enhance neuronal protection, and promote osteoclast formation. Several drugs have been designed to specifically target ER in ER-positive (ER+) breast cancer, including selective estrogen receptor modulators (SERM) such as Tamoxifen. However, the emergence of drug resistance in ER+ breast cancer and the potential side effects on the endometrium which has high ER expression has posed significant challenges in clinical practice. Recently, novel ER-targeted drugs, namely, selective estrogen receptor degrader (SERD) and selective estrogen receptor covalent antagonist (SERCA) have shown promise in addressing these concerns. This paper provides a comprehensive review of the structural functions of ER and highlights recent advancements in SERD and SERCA-related small molecule drugs, especially focusing on their structural optimization strategies and future optimization directions. Additionally, the therapeutic potential and challenges of novel SERDs and SERCAs in breast cancer and other ER-related diseases have been discussed.

[Spatio-temporal Variations in PM2.5and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration].

To coordinate the contradiction between economic development and environmental pollution and achieve the sustainable development of the economy and society, the spatio-temporal variations in PM2.5 were analyzed based on PM2.5 concentration and meteorological data of the Yangtze River Delta (YRD) urban agglomeration. Wavelet transform coherence (WTC), partial wavelet coherence (PWC), and multiple wavelet coherence (MWC) were used to analyze the multi-scale coupling oscillation between PM2.5 and meteorological factors in the time-frequency domain. The results showed that:① the concentration of PM2.5 in the YRD decreased from northwest to southeast, and the spatial range with high PM2.5 concentration decreased annually. The spatial distribution characteristics of the seasonal average PM2.5 concentration were similar to those of the annual average PM2.5 concentration. PM2.5 concentration exhibited the seasonal variation characteristics of high in winter, low in summer, and transitioning between spring and autumn. ② PM2.5 concentration decreased from 2015 to 2021, and the compliance rate increased. The difference in annual average PM2.5 concentration was decreased with dynamic convergence characteristics. The convergence of PM2.5 concentration in summer was greater than that in winter. During the whole study period, the daily average PM2.5 concentration showed a "U" distribution, and the proportion of days with excellent and good PM2.5 levels were 49.72% and 41.45%, respectively. ③ The wavelet coherence between PM2.5 and meteorological factors was different in different time-frequency domains. The main factors affecting PM2.5 were different in different time-frequency scales. At all time-frequency scales, WTC and PWC showed that wind speed and temperature were the best explanatory variables of PM2.5 variation, respectively. ④ The larger the time-frequency scale, the stronger the interaction of multi-factor combinations to explain PM2.5 variations. The synergistic effect of temperature and wind speed could better explain the variation in PM2.5. These results can provide reference for air pollution control in the YRD.

Gut microbiota interacts with inflammatory responses in acute pancreatitis.

Acute pancreatitis (AP) is one of the most common acute abdominal conditions, and its incidence has been increasing for years. Approximately 15-20% of patients develop severe AP (SAP), which is complicated by critical inflammatory injury and intestinal dysfunction. AP-associated inflammation can lead to the gut barrier and function damage, causing dysbacteriosis and facilitating intestinal microbiota migration. Pancreatic exocrine deficiency and decreased levels of antimicrobial peptides in AP can also lead to abnormal growth of intestinal bacteria. Meanwhile, intestinal microbiota migration influences the pancreatic microenvironment and affects the severity of AP, which, in turn, exacerbates the systemic inflammatory response. Thus, the interaction between the gut microbiota (GM) and the inflammatory response may be a key pathogenic feature of SAP. Treating either of these factors or breaking their interaction may offer some benefits for SAP treatment. In this review, we discuss the mechanisms of interaction of the GM and inflammation in AP and factors that can deteriorate or even cure both, including some traditional Chinese medicine treatments, to provide new methods for studying AP pathogenesis and developing therapies.

Quantifying the scale-dependent relationships of PM2.5 and O3 on meteorological factors and their influencing factors in the Beijing-Tianjin-Hebei region and surrounding areas.

To investigate the variations of PM2.5 and O3 and their synergistic effects with influencing factors at different time scales, we employed Bayesian estimator of abrupt seasonal and trend change to analyze the nonlinear variation process of PM2.5 and O3. Wavelet coherence and multiple wavelet coherence were utilized to quantify the coupling oscillation relationships of PM2.5 and O3 on single/multiple meteorological factors in the time-frequency domain. Furthermore, we combined this analysis with the partial wavelet coherence to quantitatively evaluate the influence of atmospheric teleconnection factors on the response relationships. The results obtained from this comprehensive analysis are as follows: (1) The seasonal component of PM2.5 exhibited a change point, which was most likely to occur in January 2017. The trend component showed a discontinuous decline and had a change point, which was most likely to appear in February 2017. The seasonal component of O3 did not exhibit a change point, while the trend component showed a discontinuous rise with two change points, which were most likely to occur in July 2018 and May 2017. (2) The phase and coherence relationships of PM2.5 and O3 on meteorological factors varied across different time scales. Stable phase relationships were observed on both small- and large-time scales, whereas no stable phase relationship was formed on medium scales. On all-time scales, sunshine duration was the best single variable for explaining PM2.5 variations and precipitation was the best single variable explaining O3 variations. When compared to single meteorological factors, the combination of multiple meteorological factors significantly improved the ability to explain variations in PM2.5 and O3 on small-time scales. (3) Atmospheric teleconnection factors were important driving factors affecting the response relationships of PM2.5 and O3 on meteorological factors and they had greater impact on the relationship at medium-time scales compared to small- and large-time scales.

[Relationship between atherogenic index of plasma and childhood asthma]. / è¡€æµ†è‡´åŠ¨è„‰ç¡¬åŒ–æŒ‡æ•°ä¸Žå„¿ç«¥æ”¯æ°”ç®¡å“®å–˜çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma. METHODS: This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686). CONCLUSIONS: AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.

Lipid Bilayer Strengthens the Cooperative Network of a Membrane-Integral Enzyme.

Lipid bilayer provides a two-dimensional hydrophobic solvent milieu for membrane proteins in cells. Although the native bilayer is widely recognized as an optimal environment for folding and function of membrane proteins, the underlying physical basis remains elusive. Here, employing the intramembrane protease GlpG of Escherichia coli as a model, we elucidate how the bilayer stabilizes a membrane protein and engages the protein's residue interaction network compared to the nonnative hydrophobic medium, micelles. We find that the bilayer enhances GlpG stability by promoting residue burial in the protein interior compared to micelles. Strikingly, while the cooperative residue interactions cluster into multiple distinct regions in micelles, the whole packed regions of the protein act as a single cooperative unit in the bilayer. Molecular dynamics (MD) simulation indicates that lipids less efficiently solvate GlpG than detergents. Thus, the bilayerinduced enhancement of stability and cooperativity likely stems from the dominant intraprotein interactions outcompeting the weak lipid solvation. Our findings reveal a foundational mechanism in the folding, function, and quality control of membrane proteins. The enhanced cooperativity benefits function facilitating propagation of local structural perturbation across the membrane. However, the same phenomenon can render the proteins' conformational integrity vulnerable to missense mutations causing conformational diseases1,2.

Dry deposition effect of urban green spaces on ambient particulate matter pollution in China.

Particulate matter (PM) is a major source of urban air pollution that poses a serious threat to the environment and human health. This study quantified the dry deposition effect of PM2.5 and PM10 on vegetation using a mathematical model to overcome the limitations of traditional site-scale research. Additionally, multi-source satellite remote sensing products were combined to form a raster dataset to estimate the effect of dry deposition on PM2.5 and PM10 in China's urban green spaces from 2000 to 2020. The spatial and temporal changes in the long-term series were analyzed, and the influence of environmental factors on dry deposition was analyzed in combination with wavelet changes. The experimental results showed that: 1) from 2000 to 2020, the dry deposition effect of PM2.5 and PM10 on vegetation showed an initial increasing and then decreasing trend caused by the sudden drop in atmospheric pollutant particle concentration driven by local policies; 2) broad-leaved forests provided the main dry deposition effects in urban spaces, accounting for 89.22 %, indicating a need to increase the density of these forest types in urban development planning to improve air quality; and 3) PM2.5, PM10, and environmental impact factors have time-frequency scale coherences, and the coherence between PM2.5 reduction and these factors is more complex than that of PM10, with precipitation being the best variable to explain the change in PM2.5 and PM10. These findings are important for the prevention and control of urban air pollution, regional planning of green spaces, and sustainable development of cities.

Influencing factors of PM2.5 concentration in the typical urban agglomerations in China based on wavelet perspective.

PM2.5 is one of the most harmful air pollutants affecting sustainable economic and social development in China. The analysis of influencing factors affecting PM2.5 concentration is significant for the improvement of air quality. In this study, three typical urban agglomerations in China (Beijing‒Tianjin‒Hebei [BTH], the Yangtze River Delta [YRD], and the Pearl River Delta [PRD]) were studied using innovative trend analysis, a Bayesian statistical model, and partial wavelet and multiwavelet coherence to analyze PM2.5 concentration variations and multi-scale coupled oscillations between PM2.5 concentration and air pollutants/meteorological factors. The results showed that: (1) PM2.5 concentration time-series showed significant downward trends, which decreased as follows: BTH > YRD > PRD. The higher the pollution level, the greater the change trend. In BTH and the PRD, PM2.5 had obvious trends and seasonal change points; whereas, the PM2.5 time-series change point in the YRD was not obvious. (2) PM2.5 had significant intermittent resonance cycles with air pollutants and meteorological factors in different time domains. There were differences in the main controlling factors affecting PM2.5 among the three urban agglomerations. (3) The explanatory ability of air pollutant combinations for variations in PM2.5 was higher than that of meteorological factor combinations. However, the synergistic effect of air pollutants/meteorological factors could better explain the PM2.5 concentration variations on all time-frequency scales. The results of this study provide a reference for ecological improvement as well as collaborative governance of air pollution.

Gastrointestinal digestion and absorption of soybean ß-conglycinin in an early weaned piglet model: An initial step to the induction of soybean allergy.

To date, it still remains unknown how ß-conglycinin, a major soybean allergen, crosses intestinal epithelial barrier to reach immune cells. The purpose of this study was to elucidate the pathway and molecular mechanism of ß-conglycinin absorption and transport across intestinal mucosal epithelium using a ß-conglycinin allergic piglet model. Ten-day old piglets were orally sensitized with diets containing 2% and 4% ß-conglycinin. The digestion, absorption and transport of ß-conglycinin in gastrointestinal tract was investigated. The results showed that ß-conglycinin had a certain resistance to gastrointestinal digestion, and the digestion-resistant subunits and fragments were absorbed into the intestinal mucosa and then induced an anaphylaxis in early weaned piglets. The absorption occurred in the form of IgE-allergen immune complex through transcellular pathway with CD23 as the receptor. These results provided important clues for using the pathway and molecule as inhibitor target to prevent and alleviate soybean ß-conglycinin allergy in infants.

Transient receptor potential ankyrin 1 (TRPA1) modulators: Recent update and future perspective.

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that senses irritant chemicals. Its activation is closely associated with pain, inflammation, and pruritus. TRPA1 antagonists are promising treatments for these diseases, and there has been a recent upsurge in their application to new areas such as cancer, asthma, and Alzheimer's disease. However, due to the generally disappointing performance of TRPA1 antagonists in clinical studies, scientists must pursue the development of antagonists with higher selectivity, metabolic stability, and solubility. Moreover, TRPA1 agonists provide a deeper understanding of activation mechanisms and aid in antagonist screening. Therefore, we summarize the TRPA1 antagonists and agonists developed in recent years, with a particular focus on structure-activity relationships (SARs) and pharmacological activity. In this perspective, we endeavor to keep abreast of cutting-edge ideas and provide inspiration for the development of more effective TRPA1-modulating drugs.

Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway.

The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.