PurposeDepression is acknowledged to correlate with the occurrence and progression of multiple cancers. However, no study has yet systematically complied depression-related genes to construct a prognostic signature for lung adenocarcinoma (LUAD).MethodsOur study encompasses 1,276 LUAD patients from three cohorts. Consensus clustering was employed to classify patients into different depression subtypes. Then, a variety of machine-learning algorithms were utilized to construct a robust depression-related signature (DRS). Thereafter, a nomogram combining DRS with common clinical characteristics was established for prognosis. The IOBR package was used to quantify the immune landscape, whereas the oncoPredict and Connectivity Map algorithms were employed to evaluate therapeutic response. The Seurat package was applied to process single-cell data, and the Scissor algorithm was used to identify depression-associated cells. Ultimately, depression-like mouse models were constructed to detect alternations in depression-related genes. In vitro experiments were performed to explore the role of PSEN1 in the malignant behaviors of LUAD.ResultsUnsupervised clustering stratified patients into two subtypes with distinct features. DRS consisting of 14 hub depression-related genes was established using the LASSO + GBM algorithm and served as an independent prognostic indicator. The nomogram constructed with DRS demonstrated robust predictive efficacy, with a C-index of 0.778. LUAD patients in the high-risk group exhibited weaker “immune hot” features and reduced responsiveness to immunotherapy. Additionally, high-risk patients were less sensitive to conventional chemotherapy and targeted therapies. Single-cell analysis revealed that depression-associated high-risk cells displayed more malignant characteristics. Finally, qRT-PCR validated the alternations of depression-related genes in depression-like mouse models, and in vitro experiments confirmed that PSEN1 facilitated cell proliferation in LUAD.ConclusionsThe molecular profile defined by the DRS can serve as an independent overall survival predictor and improve individualized treatment and clinical decision for LUAD patients. Of which, PSEN1 may contribute to depression-induced LUAD progression.

Background: Allergic asthma is a prevalent respiratory disease in which the pro-inflammatory polarization of alveolar macrophages (AMs) driven by glycolysis plays a pivotal role. Icariin (ICA), a natural flavonoid glycoside, has mechanisms in house dust mite (HDM)-induced asthma that remain elusive. Objective: To investigate the protective effects of ICA on HDM-induced asthma and its effects on AM. Methods: An HDM-induced murine asthma model was established and treated with ICA. High-purity AMs were sorted for transcriptomic and untargeted metabolomic analysis. Surface plasmon resonance (SPR) and molecular docking were used to evaluate the binding affinity between ICA and hexokinase 2 (Hk2). The role of the Hk2/Hk3/Pgk1 pathway was validated in vitro using the Hk2 inhibitor 3-BrPA and lentiviral-mediated Hk2 overexpression. Results: ICA antagonized airway inflammation in asthmatic mice and inhibited pro-inflammatory polarization of AMs. Integrated multi-omics analysis revealed that ICA restored glycolytic homeostasis by downregulating the Hk2/Hk3/Pgk1 pathway. SPR and molecular docking confirmed that ICA directly binds to the Hk2 protein with high affinity (KD = 27.65 μM). In vitro, ICA inhibited glycolytic flux and pro-inflammatory polarization in AMs, effects that were mimicked by 3-BrPA. Crucially, the protective effects of ICA on AMs were weakened by Hk2 overexpression, confirming that ICA exerts its anti-inflammatory action via the Hk2-mediated glycolytic pathway. Conclusion: This study is the first to perform transcriptomic and metabolomic analysis on AMs from ICA-treated asthmatic mice. Findings suggest that ICA alleviates HDM-induced asthma, potentially by binding to Hk2 and modulating the Hk2/Hk3/Pgk1 pathway to regulate AMs glycolytic levels and inflammation.

Polyploidisation, creating redundant or diverged copies of the genome, is a major driving force in plant evolution, diversification and environmental adaptation, including for the kiwifruit genus (Actinidia Lindl.). We present a high-contiguity, haplotype-resolved genome assembly of the hexaploid Actinidia valvata rootstock cultivar 'Zhongmikangzhen No. 2' (ZK2), a novel rootstock and the first of its kind to receive Plant Variety Protection in China, exhibiting superior waterlogging tolerance. The assembly, ZK2, contains 174 chromosomes in 6 haplotypes (2n = 6x = 174), where > 82% of chromosomes per haplotype are telomere-capped at one or both ends, including three haplotypes achieved with 100% telomeric representation. In total, 212 055 protein-coding genes are predicted, or about 35 000 genes per haplotype on average. Our work on comparative genomics, including analyses of TE composition, collinearity, orthologs and phylogenies, strongly reveals an AABBBB subgenome structure derived from ancestral donors A. polygama (A1 and A2) and A. macrosperma (B1 to B4). Transcriptome analysis showed differential expressions between the homeologs under waterlogging stress, highlighting subgenome-specific regulatory dynamics. A key example involves an ethylene-response factor (ERF) gene: when the B1 copy of ERF was overexpressed in the kiwifruit transgenic lines, they illustrated an enhanced waterlogging resistance. In addition, this high-quality haplotype-resolved A. valvata genome assembly enables functional trait discovery, homeolog-aware genome-wide association studies, and targeted editing of beneficial alleles or homologous gene sets, supporting the breeding of resilient polyploid kiwifruit cultivars and rootstocks. This resource provides a foundation for future research in kiwifruit, particularly for rootstock-mediated crop improvement.

Background Chronic asthma features persistent airway inflammation, airway hyper-responsiveness, and structural remodeling. Macrophages, especially alternatively activated M2 cells, are key drivers of type-2 immunity and fibrosis. Icariside II (ICAII), a flavonoid from Epimedium, exhibits known anti-inflammatory properties, but its precise immunomodulatory effects on M2 macrophages in asthma remain elusive. Objective This work sought to evaluate the potential therapeutic role of ICAII using a mouse model that mimics chronic asthma and define the underlying mechanisms, with emphasis on macrophage polarization and immune-mediated tissue remodeling. Methods Chronic asthma was established in BALB/c mice through ovalbumin (OVA) sensitization and repeated exposure, followed by ICAII administration at various doses. Pulmonary function tests, histological analyses, ELISA, flow cytometry, and immunohistochemistry were employed to assess inflammation, airway remodeling, and macrophage polarization. In vitro experiments using RAW264.7 and MHS macrophage lines further investigated ICAII’s impact on M2 differentiation. Transcriptome sequencing, network pharmacology, molecular docking analyses, and validation were integrated to identify key regulatory pathways. Results ICAII improved airway resistance and compliance, alleviated inflammatory infiltration and collagen deposition, and lowered Th2 cytokines, serum IgE, and pro-fibrotic markers, with the most pronounced effects observed at 40 mg/kg. In vivo, ICAII suppressed M2 macrophage accumulation, and in vitro, it inhibited M2 differentiation, while with a divergent impact on M1 marker expression. Network pharmacology and molecular docking predicted a moderate affinity interaction between ICAII and SIRT1, which was experimentally confirmed by SPR and enzymatic activity assays. Combined with transcriptomic and pharmacological analyses, these results identified the SIRT1/NLRP3 and TGF-β/Smad3/VEGF axes as principal pathways mediating the protective effects of ICAII against chronic asthma. Specifically, the SIRT1/NLRP3 axis refers to Sirtuin1 (SIRT1)-mediated suppression of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, whereas the TGF-β/Smad3/VEGF axis represents a transforming growth factor beta-driven profibrotic signaling cascade associated with vascular endothelial growth factor. Mechanistically, ICAII enhanced SIRT1 activity, suppressed NLRP3 inflammasome-associated inflammation, and inhibited the profibrotic TGF-β/Smad3 signaling cascade and its remodeling-associated downstream effector VEGF, thereby restraining M2 macrophage polarization and tissue remodeling. Conclusion We provide the first integrated mechanistic evidence in chronic asthma that ICAII reprograms M2 macrophages via a dual-axis strategy, simultaneously activating SIRT1 to suppress the NLRP3 inflammasome and attenuating TGF-β/Smad3/VEGF-driven remodeling. Unlike previous reports that only described the broad anti-inflammatory effects of ICAII, our study uniquely links immune modulation with structural protection and further delivers direct target engagement validation. This drug-target-function continuum not only delineates a macrophage-centered paradigm for chronic asthma pathobiology but also introduces a translationally actionable mechanism to address the long-standing challenge of persistent airway remodeling and T2-high inflammation.

Small airway dysfunction (SAD) has emerged as a key but historically under-recognized component of chronic respiratory diseases, offering a potential explanation for the frequent mismatch between symptom burden and spirometric findings. Increasing evidence suggests that the distal airway compartment represents an early and clinically meaningful site of physiological disturbance across chronic obstructive pulmonary disease (COPD), asthma, and fibrotic interstitial lung disease (ILD). Characterized by elevated peripheral resistance, ventilation heterogeneity, and a tendency toward airway closure, SAD links distal pathology to gas trapping, dynamic hyperinflation, and activity-limiting dyspnea. In asthma, strong physiological and longitudinal data support SAD as a prevalent and clinically relevant phenotype associated with poor control and exacerbation risk, with partial reversibility through targeted therapy. In COPD, structural injury and loss of terminal bronchioles appear early and contribute to symptoms primarily through modifiable mechanical consequences such as hyperinflation. In fibrotic ILD, emerging structural and physiological studies indicate early distal involvement and distinct mechanical signatures, although evidence for therapeutic modification remains limited. Considered across diseases, SAD satisfies several key features of a treatable trait in that it is measurable, clinically meaningful, and closely connected to mechanisms that shape symptoms and functional limitation, even if its reversibility differs between conditions. Framing SAD within a “treatable trait” perspective may therefore provide a unifying approach to linking symptoms, physiology, and underlying pathology, and support more individualized strategies for assessment and management.

The C-repeat binding factors (CBFs) gene is essential for plants’ cold response, which could not only be induced by the inducer of CBF expression (ICE) genes but also activated the expression of the cold-regulated (COR) gene, thereby participating in the ICE-CBF-COR cold response pathway. However, this gene family and its functions in Actinidia arguta remain unclear. In this study, whole-genome identification and functional analysis of CBF family members in A. arguta were performed. Eighteen CBF genes, which were located on four chromosomes and had five tandem repeats, were identified. The proteins encoded by the genes were predicted to be located in the nucleus and cytoplasm. The results of the promoter cis-acting element analysis revealed light response elements, low-temperature response elements, and hormone (methyl jasmonate, gibberellin, salicylic acid, etc.) response elements. We analyzed collinearity with other kiwifruit genomes, and, interestingly, the number of CBF family members differed across geographic locations of A. arguta. RT-qPCR revealed that the expression of the CBF gene family differed under low-temperature treatment; specifically, we observed differences in the expression of all the genes. Based on phylogenetic relationships and RT-qPCR analysis, the expression of AaCBF4.1 (AaCBF4) was found to be highly upregulated, and the function of this gene in cold resistance was further verified via overexpression in transgenic Arabidopsis. AaCBF4-overexpressing plants showed higher tolerance to cold stress, showing a higher germination rate, higher chlorophyll content and lower relative electrolyte leakage. In addition, compared with the wild-type Arabidopsis, the overexpressing plants exhibited significantly reduced oxidative damage due to the reduction in reactive oxygen species production under cold stress. Therefore, AaCBF4 plays an important role in improving the cold resistance of Actinidia arguta and can be further used to develop kiwifruit germplasm resources with strong cold resistance.

Low temperatures severely threaten the growth and development of kiwifruit. Research has demonstrated that proteins belonging to the 14-3-3 family play a pivotal regulatory function in the ability of plants to resist stress. However, this specific roles of the genes in kiwifruit cold tolerance remain unclear. It had been identified that beta-amylase gene, AaBAM3.1, exhibits a positive regulatory effect on kiwifruit's tolerance to low temperature. In our research, we obtained the Actinidia arguta 14-3-3 gene general regulatory factor 1 (AaGRF1) from yeast one- hybrid (Y1H) screening library of the AaBAM3.1 promoter; the expression level of AaGRF1 was enhanced by low- temperature stress. Subcellular localization, Y1H and dual-LUC assay indicated that the AaGRF1 protein resides within the nucleus and possesses the ability to interact with the AaBAM3.1 promoter. Moreover, we also studied the role of AaGRF1 gene in cold resistance of kiwifruit. When AaGRF1 was overexpressed in kiwifruit, the transgenic plants exhibited enhanced cold tolerance. The level of antioxidants and soluble sugars in these plants were elevated compared to wild-type (WT) lines. RNA-seq of the transgenic and WT lines revealed that AaGRF1 might interact with genes in the 'ascorbate-glutathione' and 'starch and sucrose' pathways, thereby enhancing the cold resistance of kiwifruit. In summary, we hypothesize that the 14-3-3 gene AaGRF1 may positively modulate the cold resistance in kiwifruit by accumulating more antioxidants and soluble sugars.

Background:Few studies have investigated the relationship between baseline type 2 biomarker levels and clinical features in pediatric asthma, particularly in different asthma stages, which may inform prognosis and remission. Objective:To explore the association between baseline Th2 biomarker levels and clinical manifestations in pediatric asthma, identifying predictors of clinical remission. Methods:The study included 172 children with a mean age of 6.87 ± 3.04 years, comprising 119 asthma patients and 53 non-respiratory symptom controls. Clinical evaluations such as lung function tests, FeNO, total IgE, blood eosinophil counts, and skin tests were conducted. Serum biomarkers (TSLP, IL-4/5/13, TARC, Periostin), and IgE were measured by ELISA. Th2-high asthma (IgE >100 IU/mL and eosinophils≥140 cells/μL, n=110) was stratified into acute attack (n=48), persistent asthma (n=26), and clinical remission (n=36). Additionally, mouse models across asthma stages were established to measure TSLP levels in BALF, serum, and lung tissue, to validate its predictor value. Result:Serum TSLP was significantly elevated in acute exacerbation and persistent asthma(P<0.01). Multivariable regression confirmed its independent association with remission (OR=1.009, P=0.023). ROC analysis indicated moderate discriminative capacity of TSLP for remission (AUC=0.59, sensitivity=39.1%, specificity=59.4%). Murine models also showed TSLP levels normalization during remission. Conclusion:Serum TSLP is independently associated with clinical remission in Th2-high pediatric asthma, though its standalone predictive accuracy is moderate (AUC=0.59). Integration with lung function and IgE may form a composite biomarker panel for remission evaluation. This stratification tool may guide asthma risk stratification and personalized disease management. Longitudinal studies are warranted to validate its prognostic utility.

Kiwifruit (Actinidia Lindl.) is a valuable fruit tree species, with its cold resistance being influenced by leaf structure and various cell types. Despite significant progress in understanding the cold stress response during the last decade, the mechanisms underlying the formation of distinct cold-resistant cell types in kiwifruit, particularly at the single-cell level, remain poorly understood. In this study, single-cell RNA sequencing (scRNA-seq) of leaves from ‘Hongyang’ (HY, A. chinensis, cold sensitive) and its transgenic line with overexpressed AaBAM3.1 (designated as HT, cold resistant) was employed to construct a single-cell transcriptional atlas to investigate the cell heterogeneity of two kiwifruit genotypes exhibiting different cold resistance capacities. A total of 5,611 and 13,466 single cells were obtained from HY and HT, respectively. The cells were classified into eight clusters based on gene expression patterns, and key genes associated with specific cell types in both genotypes were identified. Notably, pseudotime trajectory analysis revealed distinct developmental paths for guard cells and mesophyll cells. Additionally, a transcription factor, AaTIFY, exhibited genotype-specific expression and negatively regulated cold resistance. In summary, these results demonstrate that scRNA-seq offers valuable insights into cell differentiation and development in kiwifruit with varying cold resistance at the single-cell level and highlights novel genes related to cold tolerance in kiwifruit.

Kiwifruit has extremely high nutritional value, but its rootstock strongly influences the physiology and metabolism of its scion fruit. Here, we evaluated the influence of a new kiwifruit rootstock, Actinidia valvata ′Zhongmikangzhen No. 2′, on the leaves and fruits of the scion A. deliciosa ′Zhongmi 2′. The leaf size, leaf mineral element contents, fruit size (single-fruit weight, longitudinal diameter and transverse diameter), and fruit quality traits (soluble sugar content, vitamin C content, total acidity and dry matter content) of ′Zhongmi 2′ grafted on ′Zhongmikangzhen No. 2′ (zk) and A. deliciosa seedling (zp) rootstock were measured at five fruit developmental stages (30, 60, 90, 120, and 150 days after flowering (DAF)). The zk fruits were significantly larger than those of zp and their leaves were also longer. The leaf length and width of the zk fruits was significantly greater than those of the zp fruits. The leaf contents of Cu, P and Mo significantly differed at 60, 120 and 120 DAF, respectively. The fruits of the two stock–scion combinations may presented different flavors. UPLC–MS/MS analysis of the fruit metabolome revealed 1697 differentially expressed metabolites. These metabolites, which were divided into multiple categories through KEGG analysis, indicated significant differences in fruit quality and resistance. Decanoic acid (decreased in zk-hard) and 9-oxononanoic acid (increased in zk-hard) may collectively affect fruit aroma. Moreover, α-linolenic acid and 12-oxo-phytodienoic acid (a precursor of jasmonic acid), both of which increase in zk-hard, contribute to increased nutritional value and are involved in the abiotic stress response, respectively. This study revealed the effects of different rootstock–scion combinations on fruit quality traits and leaf mineral elements and provides a basis for studying the mechanisms of rootstock–scion interactions.

The escalating prevalence of multidrug-resistant (MDR) gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and linezolid-resistant Enterococcus faecalis, highlights the critical demand for new antibacterial agents that target resistance pathways. BB-Cl-Amidine is originally considered as a peptidyl arginine deiminase inhibitor and till now, its potential antimicrobial activity has not been explored. This study sought to evaluate the antibacterial effectiveness and underlying mechanisms of BB-Cl-Amidine against MDR gram-positive pathogens. The results showed that BB-Cl-Amidine exhibited potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 25 μM to 50 μM against MRSA, E. faecalis and various of Gram-positive bacteria clinical isolates. At sub-MIC concentrations, BB-Cl-Amidine significantly reduced biofilm formation in both S. aureus and E. faecalis. Moreover, the increased permeability and depolarizing membrane potential of S. aureus was found by BB-Cl-Amidine. The antibacterial activity of BB-Cl-Amidine can be neutralized by cardiolipin (CL) and phosphatidylglycerol (PG). Furthermore, BB-Cl-Amidine exposure resulted in the abnormal expression of functional proteins correlated with the cell membranes and phospholipid metabolas. In summary, the potential antibacterial and anti-biofilm activities of BB-Cl-Amidine are demonstrated via membrane disruption, offering a promising scaffold for combating MDR Gram-positive infections.

Background Little study investigates the association between baseline type 2 biomarker levels and clinical features in children diagnosed with asthma. Characterizing clinical remission in Th2-high asthma could offer valuable insights into asthma prognosis. Objectives The study aims to investigate the association of baseline type 2 biomarker levels and clinical features in children with asthma, and to identify predictors of clinical remission of asthma in children. Methods A total of 172 children with baseline age of 6.87 ± 3.04 (mean ± SD) years were enrolled in the study including 119 with physician-diagnosed asthma who regularly attended a pediatric asthma center and 53 control subjects with no respiratory symptoms. Clinical tests included lung function examination, Fraction of exhaled NO (FeNO), total IgE, blood eosinophil, and skin test. Serum Th2 biomarkers were examined by ELISA. The enrolled patients have readjusted into Th2-high asthma according to clinical eosinophil count and total IgE, and Th2-high asthma subjects were further classified into acute attack asthma, persistent asthma, and clinical remission according to the recent GINA guidelines and clinical evaluation. To verify our results, the concentration of TSLP levels was measured in BALF, serum, and lung tissue by ELISA in mouse models. Results Compared with asthma and control groups, eosinophil counts and blood eosinophils (%) were significant, whereas, no correlation was observed between asthma subjects and controls including Th2 biomarkers, gender, or ages. Positive correlations were observed between Th2 inflammatory biomarkers (TSLP, TRAC IL-5, IL-13, and Periostin) at baseline. Th2-high asthma (n = 110) was defined based on clinical measurement of IgE > 100 IU/ml and a blood eosinophil count ≥ 140 cells/µl. Among those Th2-high asthma subjects, there were 48 in acute exacerbation (43.6%), and 36 in clinical remission (32.7%), 26 were clinical asthma persistence (23.6%). Lung function and serum TSLP had marked significance among the three categories. Compared with clinical remission asthmatic subjects and controls, serum TSLP levels were significantly higher in subjects experiencing acute exacerbation and subjects defined as asthma persistence. Spearman’s correlation outlined that serum TSLP levels were related to Total IgE (IU/mL), FEV1/FVC ratio, and FEF25-75, pred %. Multivariate logistic regression analysis demonstrated that serum TSLP levels were associated with clinical remission in Th2-high asthma children (OR = 1.009; 95% CI, 1.0087–1.0086 P = 0.023<0.05). It is also revealed that serum TSLP levels may help evaluate clinical remission in Th2-high asthma when using ROC curves analysis (AUC = 0.5887, 95% CI: 0.5052 to 0.7038, P < 0.05). A cutoff value of 373.363 pg/mL was found with the highest clinical sensitivity and specificity. PPV, and NPV were 100%, 39.1%, and 59.4%, 100% in two groups, respectively. However, there were no positive results in the analysis of multivariable logistic regression in determining the predictors of persistence in Th2-high asthma. In BALF mouse, TSLP concentration had no statistically significant change in the acute and remission stages when compared to the control, but it did increase noticeably in the chronic stage ( P < 0.001).

BACKGROUND:Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS:The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS:ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS:ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.

The Wnt/β-catenin signaling pathway is highly conservative. β-catenin is the key molecule in this pathway. The β-catenin target genes regulate cell proliferation and apoptosis. Since Wnt pathway proteins are distributed on the cell membrane, cytoplasm, and nucleus, inhibiting or activating these pathway proteins presents a novel target for cancer treatment via the Wnt signaling pathway. Studies have found that this pathway plays a significant role in the formation and progression of cancers, particularly colorectal cancer. We summarised the activation and inhibition of the Wnt signaling pathway in tumors, its relationship with the microenvironment and crosstalk with other pathways, and the effect of targeting abnormal Wnt signaling in the treatment of colorectal cancer. Here is to review future targeted therapeutics in colorectal cancer research and implementation.

Background: Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airflow limitation, airway inflammation and remodeling. Icariside II (IS), derived from herbal medicine Herba Epimedii, exerts an anti-inflammatory property. However, underlying mechanisms with specifically targeted molecular expression by IS in asthma have not been fully understood, and whether IS could inhibit remodeling and EMT still remains unclear. Purpose: The study aimed to clarify therapeutic efficacy of IS for attenuating airway inflammation and remodeling in asthma, and illustrate IS-regulated specific pathway and target proteins through TMT-based quantitative proteomics. Study design and methods: Murine model of chronic asthma was constructed with ovalbumin (OVA) sensitization and then challenge for 8 weeks. Pulmonary function, leukocyte count in bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory and fibrotic cytokines, and markers of epithelial-mesenchymal transition (EMT) were evaluated. TMT-based quantitative proteomics were performed on lung tissues to explore ISregulated proteins. Results: IS contributed to alleviative airway hyperresponsiveness (AHR) evidenced by declined R-L and increased Cdyn. After IS treatment, we observed a remarked down-regulation of leukocyte count, inflammatory cytokines in BALF, and peribronchial inflammation infiltration. Goblet cell hyperplasia, mucus secretion and peribronchial collagen deposition were attenuated, with the level of TGF-ss and MMP-9 in BALF declined. Furthermore, IS induced a rise of Occludin and E-cadherin and a decline of N-cadherin and alpha-SMA in lung tissues. These results proved the protective property of IS against airway inflammation, remodeling and EMT. To further investigate underlying mechanisms of IS in asthma treatment, TMT-based quantitative proteomics were performed and 102 overlapped DEPs regulated by IS were identified. KEGG enrichment exhibited these DEPs were enriched in lysosome, phagosome and autophagy, in which LAMP2, CTSD and CTSS were common DEPs. WB, q-PCR and IHC results proofed expressional alteration of these proteins. Besides, IS could decrease Beclin-1 and LC3B expression with increasing p62 expression thus inhibiting autophagy. Conclusions: The study demonstrated IS could ameliorate AHR, airway inflammation, remodeling and EMT in OVA-induced chronic asthma mice. Our research was the first to reveal that inhibition of LAMP2, CTSD and CTSS expression in autophagy contributed to the therapeutic efficacy of IS to asthma.

Colorectal cancer is one of the most malignant cancers worldwide, and efforts have been made to elucidate the mechanism of colorectal carcinogenesis. Cellular senescence is a physiological process in cell life, but it is also found in cancer initiation and progression. Lines of evidence show that senescence may influence the development and progression of colorectal carcinogenesis. Here, the authors review the characteristics of senescence and the recent findings of a relationship between senescence and colorectal cancer.

Background:Cycloastragenol (CAG) has been reported to alleviate airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. However, its specific mechanisms remain unclear.Objective:This study is aimed at investigating the effects of CAG on asthma, comparing its efficacy with dexamethasone (DEX), and elucidating the mechanism of CAG's regulation.Methods:The asthma mouse model was induced by OVA. CAG at the optimal dose of 125 mg/kg was given every day from day 0 for 20-day prevention or from day 14 for a 7-day treatment. We observed the preventive and therapeutic effects of CAG in asthmatic mice by evaluating the airway inflammation, AHR, and mucus secretion. Lung proteins were used for TMT-based quantitative proteomic analysis to enunciate its regulatory mechanisms.Results:The early administration of 125 mg/kg CAG before asthma happened prevented asthmatic mice from AHR, airway inflammation, and mucus hypersecretion, returning to nearly the original baseline. Alternatively, the administration of CAG during asthma also had the same therapeutic effects as DEX. The proteomic analysis revealed that the therapeutical effects of CAG were associated with 248 differentially expressed proteins and 3 enriched KEGG pathways. We then focused on 3 differentially expressed proteins (ITGAL, Syk, and Vav1) and demonstrated that CAG treatment downregulated ITGAL, Syk, and Vav1 by quantitative real-time PCR, western blot analysis, and immunohistochemical staining.Conclusion:These findings suggest that CAG exerts preventive and protective effects on asthma by inhibiting ITGAL, Syk, and the downstream target Vav1.

急性胆源性胰腺炎(ABP)是最常见的急性胰腺炎(AP)类型,占AP发病人数的50％ ～70％,近年来其发病率呈上升趋势,可能与肥胖和胆结石的发病率增加有关[1].约80％的ABP患者表现为轻度自限性疾病,约20％的ABP患者临床病程严重,可导致多器官系统衰竭,死亡率高达30％[2].目前非梗阻型轻症急性胆源性胰腺炎( MABP)的早期治疗方式以保守治疗为主[3] ,而关于梗阻型MABP的治疗选择仍存在争议.本研究旨在探讨经内镜逆行性胰胆管造影术( ERCP)对梗阻型MABP的治疗效果,并探索合理的治疗策略.

Objective The expression of Wnt7a in colorectal cancer tissues and cell lines was analyzed, and the effect of Wnt7a on the proliferation of colorectal cancer cells was studied, so as to confirm the relationship between Wnt7a and the occurrence and development of colorectal cancer. Methods (1) Immunohistochemical method was used to compare the expression of Wnt7a in different tissues and its relationship with the clinicopathology of colorectal adenocarcinoma. (2) The expression levels of Wnt7a in colorectal cancer cell lines HT-29 and HCT 116 were detected by qRT-PCR. (3) The down-regulated Wnt7A expression vector was constructed, and the down-regulated Wnt7A expression cell line was established. The regeneration ability of cancer cells was detected by stem cell ball formation assay, and the influence of plate cloning assay on the proliferation ability of colorectal cancer cells was detected. Results (1) The positive rates of Wnt7a in normal colorectal mucosa, colorectal adenoma and colorectal adenocarcinoma tissues gradually increased,Wnt7a are closely related to the degree of colorectal adenocarcinoma differentiation, lymph node metastasis and Duke stage. (2) The expression level of Wnt7a in colorectal cancer cells was higher than that in normal colorectal epithelial cells. (3) The down-regulation of Wnt7A reduced the proliferation ability of colorectal cancer cells. Conclusions Wnt7a promotes the occurrence and development of colorectal adenocarcinoma.