ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma（AMR） by analyzing the changes of microstructure， chemical composition and anti-ulcerative colitis（UC） activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy（SEM-EDS）， to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products， and multivariate statistical methods including principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium（DSS）-induced UC mouse model was established. The method of disease activity index（DAI） was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin（HE） staining was used to observe the pathological changes of colon tissue， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of inflammatory factors， Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora， headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to explore the levels of short-chain fatty acids（SCFAs） in feces. Base on the above findings， this paper investigated the effects of raw and soil-fried AMR on the biological， chemical， mechanical and immune barriers of model animals， and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR， accompanied by bubble-like bulges. At the same time， there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si， Al， Mg and Ca in soil-fried AMR were significantly higher than those of raw products， and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode， a total of 132 components were identified， primarily comprising three categories of terpenoids， polyphenols and amino acids. In negative ion mode， a total of 40 components were identified， primarily polyphenolic and glycoside compounds. Among them， the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice， alleviate the shortening of colon length， reduce the levels of pro-inflammatory factors such as interleukin（IL）-17， IL-18， γ-interferon（IFN-γ） and tumor necrosis factor（TNF）-α in serum， increase the levels of anti-inflammatory factors such as secretory immunoglobulin A（sIgA）， IL-10， IL-4 and transforming growth factor-β（TGF-β） in serum， increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1（ZO-1）， Occludin， Claudin-1 and mucin 2（MUC2） in colonic mucosa， and improve the disorders of intestinal flora diversity and the levels of SCFAs（P<0.05， P<0.01）. The raw and stir-fried products of AMR also exhibited the aforementioned effects， but they were weaker than the soil-fried products. Additionally， the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.

Objective To analyze the influencing factors for postoperative anastomotic leak (AL) in carcinoma of the esophagus and gastroesophageal junction and construct a nomogram predictive model. Methods The patients who underwent radical esophagectomy at Jinling Hospital Affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were included in this study. Relevant variables were screened using univariate and multivariate logistic regression analyses. A nomogram was then developed to predict the risk factors associated with postoperative AL. The predictive performance of the nomogram was validated using the receiver operating characteristic (ROC) curve. Results A total of 468 patients with carcinoma of the esophagus and gastroesophageal junction were included in the study, comprising 354 males and 114 females, with a mean age of (62.8±7.2) years. The tumors were predominantly located in the middle or lower esophagus, and 51 (10.90%) patients experienced postoperative AL. Univariate logistic regression analysis indicated that age, body mass index (BMI), tumor location, preoperative albumin levels, diabetes mellitus, anastomosis technique, anastomosis site, and C-reactive protein (CRP) levels were potentially associated with AL (P<0.05). Multivariate logistic regression analysis identified age, BMI, tumor location, diabetes mellitus, anastomosis technique, and CRP levels as independent risk factors for AL (P<0.05). A nomogram was developed based on the findings from the multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was 0.803, indicating a strong concordance between the actual observations and the predicted outcomes. Furthermore, decision curve analysis demonstrated that the newly established nomogram holds significant value for clinical decision-making. Conclusion The predictive model for postoperative AL in patients with carcinoma of the esophagus and gastroesophageal junction demonstrates strong predictive validity and is essential for guiding clinical monitoring, early detection, and preventive strategies.

ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure （ACLF） based on sarcopenia and other clinical indicators， and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital， Capital Medical University， from January 2019 to January 2022 were enrolled， and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group， CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra （L3）， and L3 skeletal muscle index （L3-SMI） was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors， and a nomogram was developed for presentation. The area under the ROC curve （AUC） was used to assess the predictive performance of the model， the calibration curve was used to assess the degree of calibration， and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=1.962， 95% confidence interval ［CI］： 1.185‍ ‍—‍ ‍3.250， P=0.009）， total bilirubin （HR=1.003， 95%CI： 1.002‍ ‍—‍ ‍1.005， P<0.001）， international normalized ratio （HR=1.997， 95%CI： 1.674‍ ‍—‍ ‍2.382， P<0.001）， and lactic acid （HR=1.382， 95%CI： 1.170‍ ‍—‍ ‍1.632， P<0.001） were included in the sarcopenia-ACLF model. In the training cohort， the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF （0.80 vs 0.73， Z=1.97， P=0.049）. In the test cohort， the sarcopenia-ACLF model had a significantly larger AUC than MELD score （0.79 vs 0.69， Z=2.70， P=0.007） and MELD-Na score （0.79 vs 0.68， Z=2.92， P=0.004）. The calibration curve showed that the model had good calibration ability， with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities， the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients， which provides support for clinical decision-making and helps to optimize treatment strategies.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective To analyze the lung function condition and the prevalence of pulmonary ventilation disorders in the occupational population of Wuhan, and to explore their influencing factors. Methods Physical examination data from the Wuhan Prevention and Treatment Center for Occupational Diseases were used in this study, and finally 9499 people were selected as the study subjects. The linear regression model and logistic regression model were used to analyze the influencing factors of pulmonary ventilation function and pulmonary dysfunction. The restricted cubic spline was used to explore the nonlinear relationship. Results The prevalence of pulmonary ventilation disorders was 1.7%, and the lung function indexes FVC, FEV1, and FEV1/FVC were significantly lower in the population aged >27 years than in the population aged <27 years (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in females than in males (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in underweight occupational groups than in normal-weight groups (P<0.001), and FVC and FEV1 were significantly lower in dust-exposed occupational groups than in groups without dust exposure(P<0.05). Restricted cubic spline plots showed a nonlinear relationship between age and lung function indexes FVC and FEV1 (P_nonlinear< 0.05). Age and BMI were the risk factors for pulmonary ventilation disorders. Conclusion Age, gender, BMI, and dust exposure are risk factors for decreased FVC and FEV1. Age is the risk factor for decreased FEV1/FVC. Age and BMI are the risk factors for pulmonary ventilation disorders.

Chemical communication in plant-microbiome and intra-microbiome interactions weaves a complex network, critically shaping ecosystem stability and agricultural productivity. This non-contact interaction is driven by small-molecule signals that orchestrate crosstalk dynamics and beneficial association. Plants leverage these signals to distinguish between pathogens and beneficial microbes, dynamically modulate immune responses, and secrete exudates to recruit a beneficial microbiome, while microbes in turn influence plant nutrient acquisition and stress resilience. Such bidirectional chemical dialogues underpin nutrient cycling, co-evolution, microbiome assembly, and plant resistance. However, knowledge gaps persist regarding validating the key molecules involved in plant-microbe interactions. Interpreting chemical communication requires multi-omics integration to predict key information, genome editing and click chemistry to verify the function of biomolecules, and artificial intelligence (AI) models to improve resolution and accuracy. This review helps advance the understanding of chemical communication and provides theoretical support for agriculture to cope with food insecurity and climate challenges.
Microbiota/physiology* ; Plants/microbiology* ; Artificial Intelligence ; Ecosystem

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.