Development of Sinomenine Hydrochloride Sustained-release Pellet With Multiple Release Characteristics.

Due to the gastrointestinal side effects, the clinical application of sinomenine hydrochloride (SH) in rheumatoid arthritis is limited. The elderly population constitutes the primary group affected by this disease, and within this demographic, there are significant variations in gastric emptying time. To reduce the influence of individual differences on drug efficacy and concurrently alleviate gastrointestinal side effects, the SH sustained-release pellets with multiple release characteristics were developed, which comprised both regular sustained-release pellets and enteric-coated sustained-release pellets. The drug-loaded layer formulation was optimized by full factorial design. With the optimal formulation, the drug-loaded pellets achieved a yield of 96.05%, an encapsulation efficiency of 83.36% for SH, a relative standard deviation of 3.26% in SH content distribution, an average roundness of 0.971 for the pellets, and the particle size span of 0.808. The pellets with a 4 h SH release profile in an acidic environment and pellets displaying 4 h acid resistance followed by an 8 h SH release behavior in the intestinal environment were individually prepared through in vitro dissolution tests. The results demonstrated stable and compliant dissolution behavior of the formulation, along with excellent stability and physical appearance. This research offers novel insights and references for the innovative formulation of SH.

Developing diagnostic biomarkers for Alzheimer's disease based on histone lactylation-related gene.

Background: Research underscores the significant influence of histone lactylation pathways in the progression of Alzheimer's disease (AD), though the molecular mechanisms associated with histone lactylation-related genes (HLRGs) in AD are still insufficiently investigated. Methods: This study employed datasets GSE85426 and GSE97760 to identify candidate genes by intersecting weighted gene co-expression network analysis (WGCNA) module genes with AD-control differentially expressed genes (DEGs). Subsequently, machine learning refined key genes, validated by receiver operating characteristic (ROC) curve performance. Gene-set enrichment analysis (GSEA) explored the molecular mechanisms of these diagnostic markers. Concurrently, the association between the diagnostic genes and both differential immune cells and immune responses was examined. Furthermore, a ceRNA and gene-drug network was developed. Finally, the expression of the selected genes was validated using brain tissues from AD model mice. Results: This study identified five genes (ARID5B, NSMCE4A, SESN1, THADA, and XPA) with significant diagnostic utility, primarily enriched in olfactory transduction and N-glycan biosynthesis pathways. Correlation analysis demonstrated a strong positive association between all diagnostic genes and naive B cells. The ceRNA regulatory network comprised 7 miRNAs, 2 mRNAs, and 25 lncRNAs. Additionally, 33 drugs targeting the diagnostic genes were predicted. Following expression validation through training and validation sets, three genes (ARID5B, SESN1, XPA) were ultimately confirmed as biomarkers for this study. RT-qPCR and Western blot analyses revealed upregulated expression of ARID5B, SESN1, and XPA in the cerebral tissue of AD model mice. Conclusion: Three histone lactylation-linked genes (ARID5B, SESN1, XPA) were identified as potential AD biomarkers, indicating a strong association with disease progression.

Effect of Bias Arc on Microstructure and Corrosion Resistance of Q235/304 Dissimilar-Steel-Welded Joints.

To fully exploit the advantages of steel, the welding connection of dissimilar steels has been developed. In this work, the metallographic microstructures, elemental distributions, and electrochemical corrosion properties of the Q235 and 304 welds under different bias arcs were investigated. The arc bias caused the Q235-side heat-affected zone to widen, the microstructure consisted of ferrite and pearlite, and the ratio varied with decreasing distance from the fusion line. Elemental scans show that Cr and Ni concentration gradients exist near the fusion line. The 304-stainless-steel-side heat-affected zone was mainly composed of austenite grains, and the fusion zone was narrower but prone to cracking. Electrochemical tests revealed that 304 stainless steel had the best corrosion resistance, while Q235 had the worst corrosion resistance, and that the welded joints with an arc bias toward the 304 side had the best corrosion resistance. The samples' the passivation film which formed via electrochemical polarization had limited stability, but the over-passivation potential could be used as a reference for corrosion resistance. Overall, the arc bias and weld material properties significantly affected the microstructure and corrosion resistance of the joints.

In vitro digestion and fermentation of polysaccharides from nine common Polygonatum spp. and their impact on human gut microbiota.

This study aimed to investigate the dynamic changes in the physicochemical properties of polysaccharides from nine common Polygonatum spp. during in vitro simulated saliva-gastrointestinal digestion, in vitro fermentation, and their subsequent effects on human gut microbiota. Results revealed that the total sugar contents of Polygonatum spp. polysaccharides almost had little changes during the vitro digestion, and the molecular weight presented a downward trend. The in vitro digestion process produced almost no free monosaccharide, with small variations on FT-IR spectroscopy analysis. However, during the in vitro fermentation process, the polysaccharides generated remarkable changes, the total sugar showed a downward trend, and the molecular weight was degraded. There were significant changes in the monosaccharide composition, and possibly the sugar occurred isomerism. Regarding the concentrations of short-chain fatty acids, both acetic acid and propionic acid were found to be significantly elevated in the treatment group compared to the control group, and the pH value dramatically decreased. Simultaneously, Polygonatum spp. polysaccharides could remarkably modulate the richness of microbial communities and improved their diversity, especially Narrowly Defined Clostridium, and Bacteroidetes. In general, this study can be helpful to better understand the potential digestion and fermentation mechanism of the genus Polygonatum polysaccharides.

High-quality genome of a modern soybean cultivar and resequencing of 547 accessions provide insights into the role of structural variation.

Soybean provides protein, oil and multiple health-related compounds. Understanding the effects of structural variations (SVs) on economic traits in modern breeding is important for soybean improvement. Here we assembled the high-quality genome of modern cultivar Nongdadou2 (NDD2) and identified 25,814 SV-gene pairs compared to 29 reported genomes, with 13 NDD2-private SVs validated in 547 deep-resequencing (average = 18.05-fold) accessions, which advances our understanding of genomic variation biology. We found some insertions/deletions involved in seed protein and weight formation, an inversion related to adaptation to drought and a large intertranslocation implicated in a key divergence event in soybean. Of 749,714 SVs from 547 accessions, 6,013 were significantly associated with 22 yield-related and seed-quality-related traits determined in ten location × year environments. We uncovered 1,761 associated SVs that hit genes or regulatory regions, with 12 in GmMQT influencing oil and isoflavone contents. Our work provides resources and insights into SV roles in soybean improvement.

Decade-long historical shifts in legacy and emerging per- and polyfluoroalkyl substances (PFAS) in surface sediments of China's marginal seas: Ongoing production and ecological risks.

Since the addition of perfluorooctane sulfonate (PFOS) to the Stockholm Convention in 2009, it became imperative to reassess the distribution and ecological risk of per- and polyfluoroalkyl substances (PFAS) in coastal sediments over the past decade as sediment records the history of pollutants from human activities. To achieve this, sediments were collected in 2009 and 2021 from China's coastal regions. Despite the consistent geographical pattern where the highest concentrations of ∑PFAS were found in the Yellow Sea, temporal changes have emerged. During the studied period, ∑PFAS levels experienced an increase in the East China Sea while concurrently witnessing a decrease in the South China Sea. Of significance, emerging PFAS compounds displayed not only rising concentrations but also a broader array, pointing towards their intensified production and utilization within China. Alarmingly, PFOS levels in sediments taken from the East China Sea maintained a consistently high ecological risk status over the last ten years. Significant correlations were found between long-chain PFAS and organic carbon content. Comparisons between datasets from 2009 to 2021 uncovered a shifting ecological risk landscape, with heightened concerns for PFOA in the East China Sea, while PFOS-associated risks appeared to diminish in the South China Sea-potentially reflecting the transition to alternative PFAS chemicals. The research reinforces the importance of continuous monitoring and emphasizes the urgent necessity for deeper exploration into the environmental implications and hazards posed by emerging PFAS.

Fish freshness monitoring based on bilayer cellulose acetate/polyvinylidene fluoride membranes containing ZIF-8 loaded curcumin.

This study presented a dual-layer freshness indicator film produced through electrospinning, combining cellulose acetate and polyvinylidene fluoride with zeolitic imidazolate framework-8 (ZIF-8) loaded with curcumin as the indicator. Our findings demonstrated that ZIF-8 effectively preserved its metal-organic framework structure during curcumin loading, ensuring the inherent color-changing ability of curcumin. The resulting colorimetric film exhibited altered tensile properties and increased water vapor permeability. Improved light stability and storage performance were observed. Compared to single-layer films, the dual-layer structure improved the hydrophilicity and stability of the indicator film. Importantly, the introduced indicator label efficiently captured the dynamic changes of TVB-N during freshness monitoring, providing comprehensive visual information for assessing fish freshness. The synergistic properties of ZIF-8, curcumin, and the dual-layer film structure contributed to an advanced freshness indicator system, providing a multifunctional and effective approach for real-time freshness assessment of fish freshness.

Highly-stable, injectable, conductive hydrogel for chronic neuromodulation.

Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Cancer-Associated Fibroblasts: From Spectators to Protagonists in Pancreatic Cancer Progression.

Our knowledge of the origins, heterogeneity, and functions of cancer-associated fibroblasts (CAF) in pancreatic ductal adenocarcinoma (PDAC) has exponentially increased over the last two decades. This has been facilitated by the implementation of new models and single-cell technologies. However, a few key studies preceded the current exciting times in CAF research and were fundamental in initiating the investigation of CAFs and of their roles in PDAC. With their study published in Cancer Research in 2008, Hwang and colleagues have been first to successfully isolate and immortalize human pancreatic stellate cells (HPSC) from PDAC tissues. This new tool allowed them to probe the roles of CAFs in PDAC as never done before. By performing complementary in vitro and in vivo analyses, the authors demonstrated the involvement of HPSCs in PDAC malignant cell proliferation, invasion, and therapy resistance. Here, we leverage that seminal study as a framework to discuss the advances made over the last 16 years in understanding the complexity and central roles of CAFs in PDAC progression. See related article by Hwang and colleagues, Cancer Res 2008;68:918-26.

Rapid discriminant analysis for the origin of specialty yam based on multispectral data fusion strategies.

In order to achieve rapid and effective identification of Hebei yam, a qualitative discrimination model was constructed based on near infrared (NIR), mid infrared (MIR), and microscopic Raman spectra in combination with individual spectra and multispectral data fusion strategies. The results showed that the gray wolf optimizer-support vector machine (GWO-SVM) model constructed by mid-level fusion using the three feature spectra performed the best in distinguishing the geographic origin of the yam, with a prediction accuracy of 100.00% in both the training set and the test set, and an F1 score of 1.00. The results indicated that due to spectral complementarity, NIR, MIR and Raman combined with feature-level fusion can be used as a powerful, non-destructive, fast and feasible tool for geographic origin classification and brand protection of Hebei yam. This work is expected to be a potential method for origin identification analysis and quality monitoring in the food and pharmaceutical industries.

Developing multifunctional cellulose derivatives for environmental and biomedical applications: Insights into modification processes and advanced material properties.

The growing bioeconomic demand for lightweight, eco-friendly materials with functional versatility and competitive mechanical properties drives the resurgence of cellulose as a sustainable scaffold for various applications. This review comprehensively scrutinizes current progressions in cellulose functional materials (CFMs), concentrating on their structure-property connections. Significant modification methods, including cross-linking, grafting, and oxidation, are discussed together with preparation techniques categorized by cellulose sources. This review article highlights the extensive usage of modified cellulose in various industries, particularly its potential in optical and toughening applications, membrane production, and intelligent bio-based systems. Prominence is located on low-cost procedures for developing biodegradable polymers and the physical-chemical characteristics essential for biomedical applications. Furthermore, the review explores the role of cellulose derivatives in smart packaging films for food quality monitoring and deep probes into cellulose's mechanical, thermal, and structural characteristics. The multifunctional features of cellulose derivatives highlight their worth in evolving environmental and biomedical engineering applications.

Muscle-Inspired Formable Wood-Based Phase Change Materials.

Phase change materials (PCMs) are crucial for sustainable thermal management in energy-efficient construction and cold chain logistics, as they can store and release renewable thermal energy. However, traditional PCMs suffer from leakage and a loss of formability above their phase change temperatures, limiting their shape stability and versatility. Inspired by the muscle structure, formable PCMs with a hierarchical structure and solvent-responsive supramolecular networks based on polyvinyl alcohol (PVA)/wood composites are developed. The material, in its hydrated state, demonstrates low stiffness and pliability due to the weak hydrogen bonding between aligned wood fibers and PVA molecules. Through treatment of poly(ethylene glycol) (PEG) into the PVA/wood PEG gel (PEG/PVA/W) with strengthened hydrogen bonds, the resulting wood-based PCMs in the hard and melting states elevate the tensile stress from 10.14 to 80.86 MPa and the stiffness from 420 MPa to 4.8 GPa, making it 530 times stiffer than the PEG/PVA counterpart. Capable of morphing in response to solvent changes, these formable PCMs enable intricate designs for thermal management. Furthermore, supported by a comprehensive life cycle assessment, these shape-adaptable, recyclable, and biodegradable PCMs with lower environmental footprint present a sustainable alternative to conventional plastics and thermal management materials.

Effect of Continuous Infusion Therapy With Low-dose Terlipressin Combined With Norepinephrine on Hemodynamics, Inflammatory Markers, and Prognosis in Patients With Severe Septic Shock.

OBJECTIVE: The present study investigated the impact of continuous infusion therapy with low-dose terlipressin (TP) combined with norepinephrine on hemodynamics, inflammatory markers, and prognosis in patients with severe septic shock. MATERIALS AND METHODS: Seventy-four patients with severe septic shock were randomly assigned to either a control group (n = 37) or an observation group (n = 37). Patients in the control group received norepinephrine alone, while those in the observation group received a continuous infusion of low-dose TP in addition to norepinephrine. To assess the effect of treatment, a set of clinical parameters was evaluated in both groups before and after treatment. These parameters included hemodynamic indicators (heart rate [HR], mean arterial pressure [MAP], central venous pressure [CVP], cardiac index [CI], and systemic vascular resistance index [SVRI]), levels of serum inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitivity C-reactive protein [hs-CRP]), renal function indicators (blood urea nitrogen [BUN], serum creatinine [SCr], and cystatin C [Cys-C]), serum procalcitonin (PCT), and lactate, as well as lactate clearance rate (LCR). Additionally, the acute physiology and chronic health evaluation II (APACHE II) score, 28-day mortality rate, multiple organ dysfunction syndrome (MODS) incidence rate, and adverse reaction incidence were also determined. RESULTS: Compared to baseline values, MAP, CVP, CI, SVRI, and LCR increased in both groups after treatment, while HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate all decreased. Additionally, APACHE II scores also decreased. Furthermore, the observation group exhibited higher MAP, CVP, CI, SVRI, and LCR, along with lower HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate than the control group after treatment. The observation group also had lower APACHE II score, 28-day mortality rate, MODS incidence rate, and adverse reaction incidence than the control group after treatment (P < .05). CONCLUSION: Continuous infusion therapy with low-dose TP combined with norepinephrine was effective in treating patients with severe septic shock, improving hemodynamic parameters, reducing the levels of inflammatory markers, promoting renal function recovery, and reducing the mortality rate.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases.

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Rapid and non-destructive identification of Panax ginseng origins using hyperspectral imaging, visible light imaging, and X-ray imaging combined with multi-source data fusion strategies.

The geographical origin of Panax ginseng significantly influences its nutritional value and chemical composition, which in turn affects its market price. Traditional methods for analyzing these differences are often time-consuming and require substantial quantities of reagents, rendering them inefficient. Therefore, hyperspectral imaging (HSI) in conjunction with X-ray technology were used for the swift and non-destructive traceability of Panax ginseng origin. Initially, outlier samples were effectively rejected by employing a combined isolated forest algorithm and density peak clustering (DPC) algorithm. Subsequently, random forest (RF) and support vector machine (SVM) classification models were constructed using hyperspectral spectral data. These models were further optimized through the application of 72 preprocessing methods and their combinations. Additionally, to enhance the model's performance, four variable screening algorithms were employed: SelectKBest, genetic algorithm (GA), least absolute shrinkage and selection operator (LASSO), and permutation feature importance (PFI). The optimized model, utilizing second derivative, auto scaling, permutation feature importance, and support vector machine (2nd Der-AS-PFI-SVM), achieved a prediction accuracy of 93.4 %, a Kappa value of 0.876, a Brier score of 0.030, an F1 score of 0.932, and an AUC of 0.994 on an independent prediction set. Moreover, the image data (including color information and texture information) extracted from color and X-ray images were used to construct classification models and evaluate their performance. Among them, the SVM model constructed using texture information from X -ray images performed the best, and it achieved a prediction accuracy of 63.0 % on the validation set, with a Brier score of 0.181, an F1 score of 0.518, and an AUC of 0.553. By implementing mid-level fusion and high-level data fusion based on the Stacking strategy, it was found that the model employing a high-level fusion of hyperspectral spectral information and X-ray images texture information significantly outperformed the model using only hyperspectral spectral information. This advanced model attained a prediction accuracy of 95.2 %, a Kappa value of 0.912, a Brier score of 0.027, an F1 score of 0.952, and an AUC of 0.997 on the independent prediction set. In summary, this study not only provides a novel technical path for fast and non-destructive traceability of Panax ginseng origin, but also demonstrates the great potential of the combined application of HSI and X-ray technology in the field of traceability of both medicinal and food products.

Initial trajectory design of low-thrust spacecraft considering attitude constraints.

The fuel carried by deep space exploration spacecraft is crucial for the completion of their exploration missions, and the fuel for attitude control engines is even more precious. In order to reduce the control requirements for attitude control systems, this paper proposes a shape-based trajectory optimization algorithm that considers attitude constraints for low-thrust spacecraft. This method obtains a more accurate transfer trajectory by considering the change rate and change range constraints of the propulsion acceleration direction of spacecraft. By comparing the simulation results without considering spacecraft attitude constraints, it is confirmed that the proposed algorithm considering attitude constraints is very important for the initial design of transfer trajectories. This is of great significance for high-precision initial trajectory optimization of deep space exploration missions.

Baduanjin Exercise Improves Cognitive Function in Older Adults With Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

ABSTRACT: As a nonpharmacological method for cognitive rehabilitation, older adults with mild cognitive impairment (MCI) may benefit from Baduanjin exercise (BE), a moderate-intensity aerobic exercise. This meta-analysis was conducted to determine if BE is effective in enhancing cognitive performance in older adults with MCI. Using a combination of topic phrases and free words, systematic searches were executed in nine databases. Review Manager 5.4 was used to retrieve and statistically evaluate the data. Fourteen randomized controlled studies comprising 994 individuals aged ≥60 years were included in the meta-analysis. BE enhanced the general cognitive performance in individuals with MCI as measured by the Montreal Cognitive Assessment (standardized mean difference [SMD] = 2.56; 95% confidence interval [CI], 2.17, 2.96; p < 0.001). The level of memory decline (Wechsler Memory Scale; SMD = 12.46; 95% CI, 8.36, 16.57; p < 0.001), executive function (Trail Making Test; SMD = -7.08; 95% CI, -11.21, -2.94; p < 0.001), and frailty (Edmonton Frailty Scale; SMD = -0.97; 95% CI, -1.30, -0.64; p < 0.001) were all improved with BE for older adults with MCI. This study presented a therapeutic practice guide for using BE for cognitive rehabilitation in older adults. BE notably improves cognitive function in older adults with MCI and can be an excellent nonpharmaceutical therapy option.

Genome-Wide Identification and Functional Analysis of the Genes of the ATL Family in Maize during High-Temperature Stress in Maize.

Maize is a significant food and feed product, and abiotic stress significantly impacts its growth and development. Arabidopsis Toxicosa en Levadura (ATL), a member of the RING-H2 E3 subfamily, modulates various physiological processes and stress responses in Arabidopsis. However, the role of ATL in maize remains unexplored. In this study, we systematically identified the genes encoding ATL in the maize genome. The results showed that the maize ATL family consists of 77 members, all predicted to be located in the cell membrane and cytoplasm, with a highly conserved RING domain. Tissue-specific expression analysis revealed that the expression levels of ATL family genes were significantly different in different tissues. Examination of the abiotic stress data revealed that the expression levels of ATL genes fluctuated significantly under different stress conditions. To further understand the biological functions of maize ATL family genes under high-temperature stress, we studied the high-temperature phenotypes of the maize ZmATL family gene ZmATL10 and its homologous gene AtATL27 in Arabidopsis. The results showed that overexpression of the ZmATL10 and AtATL27 genes enhanced resistance to high-temperature stress.

Protocol for the characterization of the pancreatic tumor microenvironment using organoid-derived mouse models and single-nuclei RNA sequencing.

Single-nuclei RNA sequencing (snRNA-seq) allows for obtaining gene expression profiles from frozen or hard-to-dissociate tissues at the single-nuclei level. Here, we describe a protocol to obtain snRNA-seq data of pancreatic tumors from orthotopically grafted organoid-derived mouse models. We provide details on the establishment of these mouse models, the isolation of single nuclei from pancreatic tumors, and the analysis of the snRNA-seq datasets. For complete details on the use and execution of this protocol, please refer to Mucciolo et al.1.