This study aims to compare multi-disciplinary team-based learning (MDTBL), problem-based learning (PBL) and lecture-based learning (LBL) on the learning outcomes and experiences of medical students. A randomized controlled study was designed to recruit 30 medical students with a minimum of one year of clinical experience and 45 with less than one year of clinical experience to take a course on clinical diagnosis and evaluation of pulmonary nodules from September 15, 2022, to December 31, 2023. The participants were randomly assigned to the MDTBL group, PBL group, and LBL group to complete a full-course curriculum. Before, during, and after the learning phases, all participants underwent identical theoretical assessments and received a score on their learning progress. In the MDTBL and PBL groups, group discussions were permitted. After the completion of the learning phase, self-evaluation and course satisfaction were assessed through a questionnaire. The authors collected basic information on participants to ensure comparability between groups. All groups showed significant improvement in their competence in the clinical diagnosis and evaluation of pulmonary nodules, with the MDTBL group demonstrating notably higher gains in theoretical knowledge and case analysis skills (P < 0.05). The learning participation scale indicated that student engagement in the MDTBL group was higher than in the other two groups (P < 0.05). Additionally, the MDTBL group perceived the course as more engaging and enjoyable. This study demonstrates that the MDTBL teaching model, as an innovative approach, excels in enhancing knowledge acquisition, collaborative skills, and clinical practice application skills in medical students. It positions itself as a valuable teaching model for future medical education, providing educators with a new toolkit for training specialists. This study was retrospectively registered in 2023 as No.JG2023-0203.

CD26 (DPP4) is shown in literature to be implicated in multiple tumors and antitumor immunity, yet its pan-cancer and context-dependent roles remain imprecisely defined. This study comprehensively characterizes the clinical relevance of CD26 and its association with invasion-related features and immunotherapy-relevant immune infiltration and response-associated biomarkers, and to validate key findings in breast cancer cells. The integrated pan-cancer analysis of CD26 was performed using public databases, assessing its expression patterns, associations with cancer staging and prognostic value. Co-expression and protein-interaction data were used for GO/KEGG enrichment to infer potential biological pathways. Correlations between CD26 and immune cell infiltration, cancer-associated fibroblasts (CAFs), immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigen load were systematically evaluated. R software and online bioinformatics tools were employed. Additionally, qPCR, western blot and other in-vitro experiments compared CD26 expression in MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells, and examined the effects of pharmacologic CD26 inhibition (alogliptin) on proliferation, invasion, and MMP9 expression in vitro. CD26 exhibited broad but low tissue specificity and was significantly upregulated in multiple malignancies compared with normal tissues, particularly in highly aggressive tumors (P < 0.01). Higher CD26 expression was associated with advanced pathological stage and adverse prognosis in several tumor types (p < 0.01), including breast cancer, while exhibiting a favorable prognostic association in a subset of tumors, indicating context-dependent relationships. Functional enrichment suggested involvement of CD26-related networks in chemokine signaling and EMT-related processes. CD26 expression correlated with estimated immune infiltration in 34 of 38 tumor types, including CD4+ and CD8+ T cells and CAFs, and was associated with multiple immune checkpoints, as well as TMB, MSI and neoantigens in selected cancers. In vitro, CD26 was elevated in MCF-7 versus MCF-10A cells (p < 0.05), and alogliptin treatment reduced MCF-7 cell proliferation and invasion (p < 0.05), accompanied by decreased MMP9 expression (p < 0.05). This study presents an integrative pan-cancer framework linking CD26 expression to immune infiltration, together with in vitro observations in breast cancer cells, offering a comprehensive pan-cancer and experimental characterization of CD26. CD26 might be a novel prognostic biomarker candidate and therapeutic target to counteract tumor development in highly aggressive cancer.

Antimicrobial peptides (AMPs) are promising alternatives to overcome antimicrobial resistance (AMR). However, precise construction of an AMP targeting bacterial cell membranes derived from natural peptides remains a great challenges. Although the artificial intelligence (AI) algorithm-assisted screening method has achieved unprecedented successes, it's difficult to predict the targets of AMPs obtained from this method. To address this, an AMP (P 3-3R-8I) based on several natural peptides derived from insect cuticle was constructed precisely via amino acid mutation. The mutated amino acids Arginine (R) and Isoleucine (I) are expected to target the bacterial cell membranes. Surprisingly, P 3-3R-8I exhibits super antibacterial capability against two representative bacteria: methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), which could be attributed to the ability to quickly penetrate bacterial cell membranes and then to bind to bacterial DNA of P 3-3R-8I, resulting in the suppression of DNA replication. In rats' model, the MRSA-infected wound could be alleviated by P 3-3R-8I obviously, as well as lung and spleen infections in MRSA-induced systemic sepsis. Our findings provide a prospect for the precise construction of AMPs targeting bacterial cell membranes as well as a means of overcoming AMR, offering a strategy for drug-resistant bacteria-induced tissue repair.

Neoadjuvant chemoimmunotherapy (NCIT) has shown promising activity in locally advanced esophageal squamous cell carcinoma (ESCC), but comparative evidence against neoadjuvant chemotherapy (NCT) alone remains limited. This study aimed to compare the pathological response and perioperative safety of NCIT versus NCT in patients with locally advanced ESCC. This single-center retrospective cohort study included 199 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy between 2017 and 2023. Among them, 131 patients received NCIT and 68 received NCT alone. Pathological response was assessed using major pathological response (MPR), pathological complete response (pCR), and tumor regression grade (TRG). Treatment-related adverse events (TRAEs) and postoperative outcomes, including 30-day and 90-day mortality, were evaluated. To reduce confounding from baseline imbalance, 1:1 propensity score matching (PSM) was performed as the primary adjusted analysis. In the overall cohort, MPR was achieved in 51 of 131 patients in the NCIT group and 17 of 68 patients in the NCT group (38.93

BACKGROUND:Lung ischemia-reperfusion injury (LIRI) is a complex pathophysiological process with few existing therapeutic options. New drugs are needed to target both oxidative stress and enhanced sterile inflammation during ischemia-reperfusion. RESULTS:In this study, we developed a metal-phenolic nanozyme (CurFe) that possesses significant enzyme-like activities, including superoxide dismutase (SOD)-like activity and hydroxyl radical (•OH) scavenging ability, and can effectively modulate inflammatory cytokines and maintain cellular homeostasis in vitro. In the mouse LIRI model, nebulized inhalation of Cur-Fe nanozyme significantly reduced lung inflammation and oxidative stress, improved lung tissue function, and restored alveolar structure. It is important to note that transcriptomics and metabolomics analyses demonstrated that Cur-Fe nanozyme modulated key metabolic pathways, including the cGMP-PKG signaling pathway and amino acid metabolism, thereby promoting its protective effects on lung tissue. CONCLUSION:In this study, we present a Cur-Fe nanozyme that shows great potential in mitigating LIRI-associated lung injury by targeting oxidative stress and inflammation as well as regulating key transcriptional and metabolic pathways. This innovative approach provides a new avenue for the development of nanomedicines for the treatment of ischemia-reperfusion-related diseases with promising clinical applications.

BACKGROUND:Previous targeted therapies for non-small cell lung cancer (NSCLC) have focused on targeting driver mutations (e.g., EGFR/ALK), leading to approximately 30-40% of patients with negative mutations lacking effective treatments. Therefore, there is an urgent need for innovative therapeutic strategies for these patients. METHODS:CD26-targeted proteolysis-targeting chimeras (PROTACs: P4-1 to P4-4) were designed and synthesised. The binding strengths between degraders and CD26 were evaluated through surface plasmon resonance (SPR). The ternary complex formations were confirmed by NanoBRET™ live-cell ternary complex profiling assay. Driver-negative NSCLC (NCI-H460 and NCI-H1299) and BEAS-2B cells were used to study the degradation performances of degraders. The therapeutic efficacies of the optimal degrader (P4-3) were assessed via cell line-derived xenografts (CDX), in situ lung cancer and patient-derived organoids (PDOs) models. Mechanistic studies incorporated co-immunoprecipitation, immunofluorescence, reactive oxygen species (ROS)/DNA damage detection, apoptosis assays and transcriptomics. FINDINGS:CD26 underwent clathrin-dependent endocytosis induced by P4-3 and ternary complex were formed before protein degradation. Degradation of CD26 by P4-3 resulted in the cytoplasmic translocation of membrane-bound adenosine deaminase (ADA), leading to adenosine depletion, mitochondrial ROS accumulation, metabolic stress, DNA damage, and intrinsic apoptosis in vitro, in vivo and in PDOs (negative mutations) models. Mechanistically, degradation of CD26 uniquely eliminates both its enzymatic activity and non-enzymatic functions, achieving a dual effect unattainable with conventional inhibitors. INTERPRETATION:Targeted CD26 degradation represents a valuable therapeutic strategy for driver-negative NSCLC. And this approach also addresses the limitations of driver mutation-targeted based therapies, providing a promising method for NSCLC patients with negative mutations. FUNDING:This study was funded by the Key Research and Development Project of Shaanxi Province (2023-YBSF-292), the opening foundation (M2022-3) from Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, Ministry of Education, Qingdao University of Science and Technology, the National Natural Science Foundation of China (82102976, 52203337), the Youth Top Talent Program (11301223010722) from Xi'an Jiaotong University, the Key Research and Development Project of Shaanxi Province (2024SF-ZDCYL-02-09) and Capacity Improvement Plan of Shaanxi Health Committee (2024PT-09).

Background:Advances in breast cancer treatment have prolonged survival, leading to an increased incidence of secondary primary lung cancer (SPLC) in survivors. This study aims to investigate the prognosis and treatment strategies for patients with recurrent early-stage lung cancer histories and establish predictive models to guide clinical practice. Methods:This study analyzed clinical data from 2,775 patients (2008-2024) extracted from the SEER database and 15 patients (2008-2024) from the cancer registry of the First Affiliated Hospital of Xi'an Jiaotong University. The analysis focused on comparing clinical characteristics, prognosis, and chemotherapy benefits between early-stage second primary lung cancer (SPLC) patients with a history of breast cancer and those with primary lung cancer. The average age of patients in the SEER cohort was 69.64 ± 8.89 years(31-90), while the 15 hospital-registered patients had an average age of 67.15 ± 9.12 years(43-77). We employed neural network-based machine learning methods to develop models for predicting treatment decisions. Specifically, the COX-lung and MLP-lung models were developed, with a LOG-lung model used for comparison. Results:LC patients with a prior breast cancer history had significantly poorer prognosis survival time of 93 months vs 129 months. Postoperative chemotherapy improved the prognosis for some patients; however, the population benefiting from chemotherapy exhibited specific clinical characteristics. The COX-lung and MLP-lung models accurately predicted chemotherapy beneficiaries, with the MLP-lung model achieving an AUC of 0.813 and high positive predictive value. Conclusion:SPLC with prior breast cancer do have a poorer prognosis than lung cancer patients, although postoperative chemotherapy can benefit some individuals, careful selection of patients to receive chemotherapy is still warranted. We developed COX-lung and MLP-lung models which can predict beneficiaries of chemotherapy, providing crucial insights for clinicians in formulating personalized treatment plans. The findings indicate that this patient population is heterogeneous, necessitating more individualized treatment strategies.

The catalytic activity of carbon dots (CDs) has generated significant interest regarding their potential applications within the biomedical field. However, the structure-activity relationship of CDs and their pharmacological mechanisms in disease treatment have yet to be comprehensively elucidated. In this study, two distinct types of CDs exhibiting superoxide dismutase (SOD)-like enzymatic activities are synthesized through hydrothermal (Hy-CDs) and carbonization (Ca-CDs) methods, utilizing Honeysuckle as the common carbon material precursor. Through comparative analysis, surface group modifications, and theoretical calculations, it is determined that the SOD-like enzymatic activity of CDs primarily originated from the stabilizing influence of the amino group on the superoxide (center dot O2-) intermediate and its conjugation to the pi-system, facilitating electron transfer. In vitro experiments demonstrated that Hy-CDs effectively alleviated cellular oxidative stress and inhibited the secretion of pro-inflammatory cytokines. Furthermore, the significant bioactivity and catalytic properties of Hy-CDs contribute to their pronounced therapeutic efficacy in the treatment of acute lung injury (ALI) and lung ischemia/reperfusion injury (LIRI). Guided by transcriptomic analysis and Western blotting, it is demonstrated that Hy-CDs effectively inhibit Caspase11/GSDMD-dependent non-classical pyroptosis by down-regulating GBP2 protein expression, thereby contributing to lung inflammation. This study elucidates the structure-activity relationship and underlying biological mechanisms of Hy-CDs in therapeutic applications.

Molecular targeted therapy (MTT) for non-small cell lung cancer (NSCLC) has been a central issue for a long time. However, drug resistance and extra toxicity have limited its further clinical applications. Herein, taking advantages of the proteolysis-targeting chimeras (PROTACs), a series of PROTAC degraders (P4-1 to 4) targeting cell-surface CD26 (a potential target for NSCLC) have been developed for MTT of NSCLC. To achieve the efficient degradation of cell surface proteins, which is a huge challenge, the molecular structures of degraders were rational designed and optimized. Remarkably, CD26 can be degraded by P4-3 evidently at low dose (~ 500 nM) without degrading CD26 isoenzymes, which was independent of autophagy pathway. Surprisingly, the proliferation of representative NSCLC cells (NCl-H460 and NCl-H1299 cells) and tumors were significantly inhibited by P4-3, and no toxicity of P4-3 for BEAS-2B cells (human lung normal epithelial cells) were obtained. More interestingly, the powerful proliferation inhibition capabilities of P4-3 for organoids were observed. Moreover, a mechanism of P4-3 for treatment of NSCLC was proposed, which is the degradation of CD26 that induce the mitochondria-mediated apoptosis of NSCLC cells, tumors and organoids. Our exciting findings put forward instructive thoughts for the development of promising treatment strategies for NSCLC.

The emergence and proliferation of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia poses a significant global public health threat. Herein, the significant remission effect against acute MRSA pneumonia was realized through the insect cuticle protein (OfCPH-2) nanoassemblies without nonspecific immune response. The lung repair results could be attributed to the transforming of M1-type to M2-type macrophage polarization and the repression of Th17 cell differentiation in mice spleens through the intervention of OfCPH-2 nanoassemblies. These findings offer a valuable insight into the application of insect protein-based materials as effective antidrug resistant strain agents as well as a powerful strategy for acute MRSA pneumonia.

The overuse of antibiotics has led to lethal multi-antibiotic-resistant microorganisms around the globe, with restricted availability of novel antibiotics. Compared to conventional antibiotics, evolutionarily originated antimicrobial peptides (AMPs) are promising alternatives to address these issues. The gut microbiome of Blattella germanica represents a previously untapped resource of naturally evolving AMPs for developing antimicrobial agents. Using the in-house designed tool “AMPidentifier,” AMP candidates were mined from the gut microbiome of B. germanica, and their activities were validated both in vitro and in vivo. Among filtered candidates, AMP1, derived from the symbiotic microorganism Blattabacterium cuenoti, demonstrated broad-spectrum antibacterial activity, low cytotoxicity towards mammalian cells, and a lack of hemolytic effects. Mechanistic studies revealed that AMP1 rapidly permeates the bacterial cell and accumulates intracellularly, resulting in a gradual and mild depolarization of the cell membrane during the initial incubation period, suggesting minimal direct impact on membrane integrity. Furthermore, observations from fluorescence microscopy and scanning electron microscopy indicated abnormalities in bacterial binary fission and compromised cell structure. These findings led to the hypothesis that AMP1 may inhibit bacterial cell wall synthesis. Furthermore, AMP1 showed potent antibacterial and wound healing effects in mice, with comparable performances of vancomycin. This study exemplifies an interdisciplinary approach to screening safe and effective AMPs from natural biological tissues, and our identified AMP 1 holds promising potential for clinical application.

Antimicrobial peptides (AMPs) are candidates for use against antibiotic-resistant microorganisms. However, due to high cytotoxicity and poor performance in biological contexts, most AMPs are unable to satisfy the requirements. The gut microbiomes of pathogenic species like Blattella germanica represent unexploited reservoirs of naturally evolved biocompatible AMPs. Here we developed a lightweight AI pipeline called AMPidentifer with two nine-layers Dense-Net blocks and one embedded new self-attention module to enable the discovery of biocompatible AMPs from microbiome. The core structure of AMPidentifer is simple, not requiring complexing code basis. On the independent test dataset, it showed robust performance and avoided high false-positive results. From the gut microbiome of B. germanica , new AMP candidates with potential low toxicities and antimicrobial activities were identified by AMPidentifer. The selected two AMPs demonstrated good antimicrobial effects in vitro and in vivo . The Cys residue was demonstrated to perform different action mechanisms in the antimicrobial activity of two AMPs, providing insights for future rational design. New efficient AMPs with low cytotoxicity identified by the new high-throughput AI pipeline from the gut microbiome of B. germanica successfully showed an important interdisciplinary strategy for discovering bio-safe AMPs from nature. ![The Graphic Abstract][1] The Graphic Abstract ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

Background: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF.Objective: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF.Methods: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking.Results: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6.Conclusion: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

呼吸系统感染在全球所有年龄组都有较高的发病率和病死率,据统计每年全球死于下呼吸道感染的人数超过280万,是造成5岁以下儿童和65岁以上成人死亡的主要原因,带来了巨大的医疗负担[1].临床对于呼吸系统感染的治疗通常根据患者的临床表现和常规实验室检查结果作出诊断,针对呼吸系统危重症通常在留取呼吸道分泌物标本后先行经验性抗菌药物治疗,待病原学结果回报后再进行调整.但病原学诊断往往需要结合微生物培养、病理学检查、分子生物学测序等方法,耗时较长且成本较高.早期、快速、精准、无创的检查方法更有利于确定病原体,从而针对性地选择抗菌药物,控制耐药同时避免因等待检查结果而延误治疗时机.随着代谢组学的发展,呼气分析技术在临床研究中的内容逐渐丰富.本文总结了近年来呼气分析技术在呼吸系统感染领域的相关研究,表明呼气分析技术有望成为一种快速、便捷、无创的病原学诊断方式.

呼气分析技术是一种通过检测呼出气体中特征性成分的变化,从而为临床诊断提供辅助信息的检查方法.与传统方法相比,该技术具有无创伤、简捷、易实现等优点,在疾病的早期诊断与筛查过程中具有巨大潜力,但在临床医学实际应用中尚存在一些问题亟待解决.阐述呼气分析技术中呼气采集、检测方法以及在疾病诊断中的应用等三方面内容,对国内外呼吸诊断技术的发展和应用进行讨论,并对该技术目前存在的局限性和应用前景进行评述.