Extracellular vesicles (EVs) are nanoscale particles released by cells, carrying proteins, nucleic acids, lipids, and metabolites. These vesicles mediate intercellular communication and modulate disease progression across various conditions. Owing to their molecular heterogeneity and the stable bilayer protecting their cargo, EVs serve as valuable tools for early disease detection and personalized therapies. However, traditional bulk EV studies aggregate data, which can mask the distinct molecular profiles of individual EVs critical for targeted diagnostics and treatments, diminishing diagnostic precision. Recent advances in single-EV analysis, leveraging high-resolution sequencing and imaging technologies, have revealed unique molecular signatures. However, a comprehensive database integrating multi-omics data from single EVs remains lacking. To address this, we developed SVAtlas, the first database dedicated to integrating single-EV datasets (2015-2025). SVAtlas incorporates 8120 protein entries, 106 RNA entries (miRNA, mRNA, circRNA, and lncRNA), 2 DNA entries, and 8 lipid/metabolite entries across 276 EV projects, spanning 31 diseases, 32 tissues/organs, and 10 biofluids from five species. SVAtlas offers single-EV datasets with experimental parameters, heterogeneity analyses, disease-specific marker exploration, built-in analysis/clustering/visualization pipelines, and an LLM-based question-answering tool, empowering researchers to explore single-EV omics in detail. Free and accessible at https://www.svatlas.org/, SVAtlas accelerates the clinical translation of single-EV analysis and biomarker discovery.

Extracting nicotine from aqueous solution faces enormous challenges. Here, we designed a structurally stable nicotine imprinting membrane (ATP-MIM) with high adsorption efficiency and selectivity based on aminofunctionalized polyvinylidene fluoride (PVDF) for selectively recognizes nicotine. Polyacrylamide (PAM) binds with the surface and pores of (3-aminopropyl) triethoxysilane (APTES)-tetraethyl orthosilicate (TEOS)-modified PVDF membrane (A-T/PVDF) via covalent bonds, providing numerous specific sites for nicotine. The adsorption capacity of ATP-MIM for nicotine was 22.16 mg g- 1 (C0 = 600 mu g mL- 1, t = 30 min, T = 25 degrees C). After 10 cycles, the ATP-MIM has a high removal rate (78 %) of nicotine and chemical stability. The adsorption mechanism is that the interaction of hydrogen bond between nicotine and the amino groups of the ATP-MIM. Owing to its strong adsorption performance and simple preparation, ATP-MIM is a promising material for nicotine extraction from aqueous solution.

The MYC oncoprotein is a key driver of various cancers and is particularly relevant in triple-negative breast cancer (TNBC), where its dysregulated activation promotes aggressive tumor growth, metastasis, and resistance to treatment. Despite its central role in cancer development, directly targeting MYC proves challenging due to its disordered structure and lack of druggable pockets. Synthetic lethality, a strategy that exploits secondary vulnerabilities in MYC-driven cancer cells, offers a promising therapeutic approach. In this study, we establish a chemogenetic screening platform to identify compounds that selectively target MYC-driven cancer cells. We screen a library of approximately 600 kinase inhibitors and identify ALW-II-41-27, an EphA2 inhibitor, as a top hit. ALW-II-41-27 demonstrates strong MYC-selective cytotoxicity and induces apoptosis in MYC-activated cells through the intrinsic apoptotic pathway. Importantly, this apoptotic response is independent of p53 status, which is frequently inactivated by loss-of-function mutations in MYC-driven cancers. In vivo, ALW-II-41-27 effectively inhibits tumor growth in MDA-MB-231 and MDA-MB-468 TNBC xenografts without apparent toxicity. These findings highlight EPHA2 as a novel synthetic lethal partner of MYC and suggest that targeting EPHA2 could offer a promising therapeutic strategy for MYC-driven TNBC.

Programmed death-ligand 1 (PD-L1) and claudin 18.2 (CLDN18.2) are key biomarkers informing systemic therapy in advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma, yet diagnostic discordance and treatment-associated change may compromise patient selection. We characterized biopsy underestimation and biomarker evolution following neoadjuvant therapy to inform clinical testing practice. We retrospectively analyzed 554 gastrectomy patients. Diagnostic concordance was assessed in upfront surgery (n = 331), and treatment-associated biomarker change was evaluated in the neoadjuvant cohort (n = 165), using paired biopsy and resection specimens. PD-L1 (22C3) and CLDN18.2 (43-14A) were assessed by immunohistochemistry. CLDN18.2 positivity was defined as moderate-to-strong membranous staining in ≥75

Background Obesity-induced osteoporosis is a prevalent complication among obese individuals. Conventional anti-osteoporosis medications often lack therapeutic specificity and may exacerbate lipid metabolism disorders. Consequently, identifying suitable pharmacological interventions for obesity-induced osteoporosis, elucidating its underlying biological mechanisms, and developing nanodrug delivery systems with enhanced biocompatibility and targeted delivery remain significant challenges. Methods This study reveals that the pathogenesis of obesity-induced osteoporosis is primarily driven by excessive mitophagy. Notably, Exendin-4 (Ex-4) has been shown to ameliorate mitophagy and mitigate obesity-induced osteoporosis. The nanocomposite DSPE-PEG-ALN (DPA)@Neutrophil membrane (NM)@Cu-TCPP(Zn)/Ex-4 (CTZE), characterized by high biocompatibility and reactive oxygen species (ROS) responsiveness, effectively targets bone tissue, reduces ROS levels, and regulates the release of Cu2+, Zn2+, Ex-4, and Alendronate (ALN). This composite interferes with B-cell lymphoma-2 (BCL2)- Beclin-1 (BECN1) binding via the tet methylcytosine dioxygenase 2 (TET2)/PTEN-induced putative kinase protein 1 (PINK1)/Parkin (E3 ubiquitin-protein ligase parkin) pathway, thereby promoting osteoblast differentiation and mineralization. The safety and efficacy of this nano-delivery platform were validated in a mouse model of obesity-induced osteoporosis. Conclusions In summary, our study illustrates that excessive mitophagy plays a crucial role in obesity-induced osteoporosis. Furthermore, DPA@NM@CTZE exhibits significant potential for the precise treatment of obesity-induced osteoporosis, mitigating the side effects of Ex-4, and enhancing the bone microenvironment.

This study examines the impact of polyethylene terephthalate (PET) fibers on major mechanical properties of cement mortar including toughness and modulus of rupture (MOR). For this purpose, various mixes were designed and PET fibers were incorporated into mortar mixes at two dosage levels (0.5% and 1% by volume), along with two other varying parameters i.e. water-to-binder (w/b) ratios, and superplasticizer (SP) ratio to adjust the workability of the cement mixtures. The key mechanical characteristics of hardened cement composite including strength, toughness, and MOR were evaluated and a comprehensive parametric study was implemented. Besides, correlation analyses of each pair of the mechanical properties were performed and the coefficients of determination were determined. The experimental outcomes indicated that the optimum fiber volumes for compressive toughness and flexural toughness were 0.5% and 1%, respectively. While lower w/b ratios such as w/b = 0.35 resulted in higher strength properties, improved toughness was noted in higher rations. RSM analysis implemented showed that the optimum MOR can be achieved at the lowest level of w/b and middle levels of SP and Fiber%. Correlation analyses results demonstrated a strong correlation between compressive strength-toughness and compressive strength-MOR with R2 = 0.90 and R2 = 0.96, respectively. However, lower correlations were observed for flexural strength-toughness and flexural toughness-MOR with similar R2 = 0.75.

ObjectivesThe increasing prevalence of obesity underscores the need to explore its impact on assisted reproductive technology (ART) outcomes. This study aims to evaluate the association between visceral fat area (VFA), measured by bioelectrical impedance analysis (BIA), and pregnancy outcomes following frozen embryo transfer (FET).MethodsIn this retrospective clinical study, the data of 1,510 patients who underwent FET between April 2022 and April 2023 were analyzed. The VFA was measured by BIA, and patients were categorized into low and high VFA groups based on a threshold of 65 cm². Pregnancy outcomes were compared between the two groups. Univariable and multivariate logistic regression analyses, along with restricted cubic spline (RCS) modeling, were used to adjust for age, body mass index (BMI), and basal estradiol (E2) levels to determine the relationship between VFA and FET outcomes.ResultsThere were significant differences in baseline characteristics and outcomes between the two groups. The high VFA group was characterized by older age and a lower basal estradiol (E2) level. The biochemical pregnancy rate, implantation rate, clinical pregnancy rate (CPR), and live birth rate (LBR) were significantly lower in the high VFA group. Logistic regression revealed a significant negative correlation between the high VFA group and both CPR and LBR. The RCS model demonstrated that the VFA was nonlinearly correlated with CPR and LBR. Subgroup analysis showed that among individuals under 35 years of age or with a BMI < 24, high VFA was significantly associated with poorer CPR and LBR.ConclusionsHigh VFA is associated with poorer pregnancy outcomes after FET in female patients with infertility, with both CPR and LBR decreasing as VFA increases. Clinicians should consider VFA as an important reference for targeted fat management interventions to optimize reproductive success, especially when VFA exceeds 65 cm².

Small cell lung cancer (SCLC) is associated with high mortality and limited therapeutic options. There is increasing recognition that SCLC harbors molecular heterogeneity. Using a new liquid biopsy assay, it is demonstrated that SCLC subtypes, as determined by patient tumor tissue staining and cell lines, can be accurately identified by measuring the mRNA expression of subtype transcription factors (ASCL1, POU2F3, and NEUROD1) in circulating exosome-rich extracellular vesicles (Exo). Additionally, upregulation of Delta-like ligand 3 (DLL3) mRNA in Exo and its membrane protein (mProtein) in extracellular vesicles associated with tumor (tEV) may distinguish both limited- and extensive-stage SCLC patients from high-risk smokers, with AUC/ROC values of 0.836 and 0.839, respectively. By incorporating Exo-ASCL1 and Exo-POU2F3 mRNA expression with DLL3 Exo-mRNA/tEV-mProtein expression, the classifier enhances the AUC/ROC to 0.912 and 0.963 for limited- and extensive-stage SCLC patients, respectively.

Extracellular vesicles (EVs) hold promise as a new generation of noninvasive cancer diagnostic biomarkers, but the complexity and heterogeneity of clinical samples limit the detection accuracy and clinical applicability. Herein, we propose a retention-monitoring, label-free plasmonic sensing method based on a dual protein logic profiling framework nucleic acid (DP-FNA) molecular device for the specific and sensitive detection of tumor-derived EVs. The DP-FNA comprises two aptamers to determine the relative expression levels of two target proteins on single EVs through a retention-based logical profiling process. This strategy is minimally affected by the concentrations of EVs, providing significantly improved detection accuracy compared with traditional single aptamer-based assays. Using CD63/EpCAM and EpCAM/CD63 aptamer combinations, we achieved 100% accuracy in distinguishing between cancer and noncancer clinical serum samples, as well as between breast cancer and liver cancer clinical serum samples. We envision that this DP-FNA-based retention-monitoring assay will advance the potential of EVs in early cancer diagnosis.

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, it is developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of the coronavirus disease of 2019 (COVID-19). BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks.

In this paper the silver ions in a silver nitrate solution were reduced to the Ag element by silk sericin (SS); then, N-isopropylacrylamide (NIPAAm) was added into the mixed solution of SS and silver nitrate to form the bifunctional SS/NIPAAm-Ag3 hydrogel with interpenetrating network structure with N,N-methylenebisacrylamide (BIS) as a cross-linking agent, ammonium persulfate (APS) as a initiator and N, N, N', N-tetramethylethylenediamine (TEMED) as a co-initiator. SEM showed that the SS/NIPAAm-Ag3 hydrogel had a regular honeycomb structure and high porosity. It was confirmed by DSC that the SS/NIPAAm-Ag3 hydrogel exhibited temperature sensitivity, and its Lower Critical Solution Temperature (LCST) was about 35 degrees C. The swelling degree of the SS/NIPAAm-Ag3 hydrogel was obviously higher than that of SS/NIPAAm hydrogel at 25 degrees C and 37 degrees C. The time required for deswelling equilibrium was shortened by 2 h compared with SS/NIPAAm hydrogel, showing that the introduction of a certain amount of nano-Ag could give hydrogel excellent swelling and deswelling properties. The bacteriostatic rates against Esherichia coli (E.coli) and Staphylococcus aureus (S. aureus) reached 99.8% and 93.38%, respectively. A cytotoxicity test proved that SS/NIPAAm-Ag3 hydrogel had no adverse effects on the human cell health. The development of this temperature-sensitive and antibacterial hydrogel provides a new possibility for the preparation of hydrogel medical dressing.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

A gel (SNA-Ag) loaded with nanoscale silver particles and a pH-responsive agent was prepared using N-isopropyl acrylamide (NIPAAm) as the first network structure, silk sericin (SS) as the second network structure and reducing agent, alizarin as the pH indicator and co-reducing agent, N, N-methylene bisacrylamide (BIS) as the crosslinking agent, ammonium persulfate (APS) as the initiator and N, N, N, N-tetramethylethylenediamine (TEMED) as co-initiator. To improve the breaking strength of the gel, the temperature and pH-responsive antibacterial (V/SNA-Ag) composite dressing was prepared by crosslinking the SNA-Ag gel with viscose non-woven fabric using glutaraldehyde as the crosslinking agent. Fourier transform infrared spectrometer (FTIR) and scanning electron microscopy (SEM) showed that the SNA-Ag hydrogel was successfully crosslinked with the viscose non-woven fabric. Meanwhile, a gel coating was formed on the fabric, and the coating thickness increased when the crosslinking time was extended. Differential Scanning Calorimetry (DSC) and pH response tests confirmed that the dressing was temperature sensitive, and the Lower Critical Solution Temperature (LCST) of the dressing was about 35 degrees C. When the pH of the dressing was changed from acidic to alkaline, its color was changed from yellow to purple, indicating that its color presented pH response characteristics. The dressing not only had excellent swelling performance but also had outstanding antibacterial activity; the antibacterial degree for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was up to 99%. A cytotoxicity test suggested that the survival degree of mouse cells after incubation for 96 h was more than 75%, proving that it was safe and nontoxic. In addition, compared with viscose non-woven fabric, the breaking strength of composite dressing was increased, and the air permeability was decreased. In conclusion, we suggest that V/SNA-Ag composite dressings have great potential for monitoring and treating wounds.

The conceptual design stage is an indispensable and important stage in the development of the modern body. However, due to the lack of sufficient body structure parameter support, the design defects generated at this time are difficult to make up for in the subsequent design stage. Therefore, it is of great significance to develop a conceptual design software for body structure that integrates design, analysis, and optimization. This paper proposes an intelligent body frame structure modeling and optimization system based on conceptual design, S-iVCD (Intelligent System for Conceptual Design of Vehicle Body Structure). Based on deep learning methods and body design sketches, a conceptual model of body structure is quickly established. Based on the data parameters stored in the Excel table, the system is seamlessly connected to the domestic independent finite element software SIPESC to calculate the simulated working conditions. The body structure optimization module is driven by the MMA (method of moving asymptotes), and takes the body structure performance and total mass as the optimization goals or constraints of the mathematical model to achieve body structure performance improvement and lightweight design.

ObjectiveThe causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role.MethodsWe conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship.ResultsThere is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger’s test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship.ConclusionThis study’s findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.

Joule heating and electrokinetic phenomena in micro/nano-electroporation (MEP/NEP) is investigated. An ‘electroporation zone’ is defined for NEP/MEP to avoid the negative impact of Joule heating and electro-osmosis on cargo transport.

Background Cancer-associated fibroblasts (CAFs) play a pivotal role in promoting tumour progression by secreting a variety of growth factors. Among these secreted proteins, thrombospondin-2 (THBS2) is recognized as a significant prognostic indicator in various cancers. However, to date, few studies on the role of THBS2 in gastric cancer (GC) progression have been reported. Methods THBS2 expression was shown to be abnormally elevated in GC by combined transcriptomic and proteomic sequencing of GC tissues. The association between THBS2 expression and clinical outcomes of GC patients was evaluated. Primary CAFs and normal fibroblasts (NFs) were extracted from tumour tissues and paracarcinoma nontumor tissues of patients with GC. These primary cells were used to investigate the effect of CAF on the biological behavior of GC cells, which promotes GC cell metastasis. RNA sequencing was subsequently conducted to preliminarily elucidate the downstream molecular regulatory mechanism by which THBS2 promotes the metastasis of GC cells. Results THBS2 was aberrantly expressed in the stromal components of primary GC tumour tissues with lymph node metastases (IDDF2024-ABS-0370 Figure 1). The expression level of THBS2 was significantly proportional to the depth of invasion, the number of lymph node metastases, and the disease stage of gastric cancer, and predicted poor survival rate of patients after surgery (IDDF2024-ABS-0370 Figure 1). THBS2 secreted by CAF could promote the proliferation and metastasis of GC cells in vivo and in vitro (IDDF2024-ABS-0370 Figure 2). THBS2 could bind to CD36 protein on the membrane of GC cells, then activate its downstream Akt/Erk signalling pathway, which enhanced the invasion and metastasis abilities of GC cells (IDDF2024-ABS-0370 Figure 3). Conclusions The mechanism by which THBS2 secreted by CAF cells promoted the metastasis of GC cells provided a new idea for molecular targeted therapy of GC.

Biodegradable microneedles with a drug delivery channel have enormous potential for consumers, including use in chronic disease, vaccines, and beauty applications, due to being painless and scarless. This study designed a microinjection mold to fabricate a biodegradable polylactic acid (PLA) in-plane microneedle array product. In order to ensure that the microcavities could be well filled before production, the influences of the processing parameters on the filling fraction were investigated. The results indicated that the PLA microneedle can be filled under fast filling, higher melt temperature, higher mold temperature, and higher packing pressure, although the dimensions of the microcavities were much smaller than the base portion. We also observed that the side microcavities filled better than the central ones under certain processing parameters. However, this does not mean that the side microcavities filled better than the central ones. The central microcavity was filled when the side microcavities were not, under certain conditions in this study. The final filling fraction was determined by the combination of all parameters, according to the analysis of a 16 orthogonal latin hypercube sampling analysis. This analysis also showed the distribution in any two-parameter space as to whether the product was filled entirely or not. Finally, the microneedle array product was fabricated according to the investigation in this study.

Abstract The molecular heterogeneity of extracellular vesicles (EVs) and the co‐isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single‐EV and particle (siEVP) protein and RNA assay (siEVPPRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVPPRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single‐particle resolution, the siEVPPRA outperformed the sensitivities of bulk‐analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross‐validation. Despite the presence of single‐EV‐LP co‐isolates in serum, the siEVPPRA detected GBM‐associated vesicular RNA profiles in GBM patient siEVPs. The siEVPPRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise.