Full-course NIR-II imaging-navigated fractionated photodynamic therapy of bladder tumours with X-ray-activated nanotransducers.

The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis.

Sapphire-Based Optrode for Low Noise Neural Recording and Optogenetic Manipulation.

Electrophysiological recordings of neurons in deep brain regions using optogenetic stimulation are essential to understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5x2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

Ginseng rusty root symptoms result from nitric oxide stress in soil.

Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.

Germplasm Resources and Genetic Breeding of Huang-Qi (Astragali Radix): A Systematic Review.

Huang-Qi (Astragali radix) is one of the most widely used herbs in traditional Chinese medicine, derived from the dried roots of Astragalus membranaceus or Astragalus membranaceus var. mongholicus. To date, more than 200 compounds have been reported to be isolated and identified in Huang-Qi. However, information pertaining to Huang-Qi breeding is considerably fragmented, with fundamental gaps in knowledge, creating a bottleneck in effective breeding strategies. This review systematically introduces Huang-Qi germplasm resources, genetic diversity, and genetic breeding, including wild species and cultivars, and summarizes the breeding strategy for cultivars and the results thereof as well as recent progress in the functional characterization of the structural and regulatory genes related to horticultural traits. Perspectives about the resource protection and utilization, breeding, and industrialization of Huang-Qi in the future are also briefly discussed.

Evaluating the impact of ecological factors on the quality and habitat distribution of Lonicera japonica Flos using HPLC and the MaxEnt model.

Introduction: The quality of traditional Chinese medicine is based on the content of their secondary metabolites, which vary with habitat adaptation and ecological factors. This study focuses on Lonicera japonica Flos (LJF), a key traditional herbal medicine, and aims to evaluate how ecological factors impact its quality. Methods: We developed a new evaluation method combining high-performance liquid chromatography (HPLC) fingerprinting technology and MaxEnt models to assess the effects of ecological factors on LJF quality. The MaxEnt model was used to predict suitable habitats for current and future scenarios, while HPLC was employed to analyze the contents of key compounds. We also used ArcGIS for spatial analysis to create a quality zoning map. Results: The analysis identified 21 common chromatographic peaks, with significant variations in the contents of Hyperoside, Rutin, Chlorogenic acid, Cynaroside, and Isochlorogenic acid A across different habitats. Key environmental variables influencing LJF distribution were identified, including temperature, precipitation, and elevation. The current suitable habitats primarily include regions south of the Yangtze River. Under future climate scenarios, suitable areas are expected to shift, with notable expansions in southern Gansu, southeastern Tibet, and southern Liaoning. The spatial distribution maps revealed that high-quality LJF is predominantly found in central and southern Hebei, northern Henan, central Shandong, central Sichuan, southern Guangdong, and Taiwan. Discussion: The study indicates that suitable growth areas can promote the accumulation of certain secondary metabolites in plants, as the accumulation of these metabolites varies. The results underscore the necessity of optimizing quality based on cultivation practices. The integration of HPLC fingerprinting technology and the MaxEnt model provides valuable insights for the conservation and cultivation of herbal resources, offering a new perspective on evaluating the impact of ecological factors on the quality of traditional Chinese medicines.

An Integrated Neural Optrode with Modification of Polymer-Carbon Composite Films for Suppression of the Photoelectric Artifacts.

Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 µLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience.

One stone two birds - Submucosal tunneling endoscopic resection for a large esophageal submucosal mass and esophageal diverticulum.

A-35-year-old woman presented our hospital with half a year's history of solid food dysphagia. An upper gastrointestinal endoscopy revealed a large submucosal mass in an esophageal diverticulum near the gastroesophageal junction. Endoscopic ultrasound (EUS) confirmed a hypoechoic lesion arising from the muscularis propria layer with the size of 25*14 mm. Therefore, submucosal tunneling endoscopic resection (STER) was proposed to remove the large submucosal lesion in addition to targeted septotomy of the esophageal diverticula. A 2-cm longitudinal mucosal access was made at 3 cm above the submucosal lesion, and a submucosal longitudinal tunnel was created until the submucosal lesion revealed using a DualKnife (Olympus, Japan). Meticulous resection was performed with the DualKnife, and the lateral border of the lesion was dissected from muscularis propria layer. It was completely removed the lesion with en bolc resection, and dissected the septum of the diverticulum using the DualKnife. The tunnel access was closed with several hemoclips. Finally, it has been demonstrated to achieve a perfect outcome for the patient. The patient was discharged three days later with symptom resolved on follow-up and to date.

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters.

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.

Predicting the Potential Distribution of Hypericum perforatum under Climate Change Scenarios Using a Maximum Entropy Model.

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.

Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients-Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats.

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

Mining Bovine Milk Proteins for DPP-4 Inhibitory Peptides Using Machine Learning and Virtual Proteolysis.

Dipeptidyl peptidase-IV (DPP-4) enzyme inhibitors are a promising category of diabetes medications. Bioactive peptides, particularly those derived from bovine milk proteins, play crucial roles in inhibiting the DPP-4 enzyme. This study describes a comprehensive strategy for DPP-4 inhibitory peptide discovery and validation that combines machine learning and virtual proteolysis techniques. Five machine learning models, including GBDT, XGBoost, LightGBM, CatBoost, and RF, were trained. Notably, LightGBM demonstrated superior performance with an AUC value of 0.92 ± 0.01. Subsequently, LightGBM was employed to forecast the DPP-4 inhibitory potential of peptides generated through virtual proteolysis of milk proteins. Through a series of in silico screening process and in vitro experiments, GPVRGPF and HPHPHL were found to exhibit good DPP-4 inhibitory activity. Molecular docking and molecular dynamics simulations further confirmed the inhibitory mechanisms of these peptides. Through retracing the virtual proteolysis steps, it was found that GPVRGPF can be obtained from ß-casein through enzymatic hydrolysis by chymotrypsin, while HPHPHL can be obtained from κ-casein through enzymatic hydrolysis by stem bromelain or papain. In summary, the integration of machine learning and virtual proteolysis techniques can aid in the preliminary determination of key hydrolysis parameters and facilitate the efficient screening of bioactive peptides.

Analysis of ginseng rusty root symptoms transcriptome and its pathogenesis directed by reactive oxygen species theory.

Ginseng rusty root symptoms (GRS) is a primary disease of ginseng, which seriously decreases the yield and quality of ginseng and causes enormous losses to ginseng production. GRS prevention and control is still challenging due to its unclear etiology. In this study, the phloem tissue of healthy Panax ginseng (AG), the nonred tissue of the phloem epidermis around the lesion (BG), and the red lesion site tissue of GRS (CG) were extracted for mRNA transcriptomic analysis; 35,958 differentially expressed genes (DEGs) were identified and were associated with multiple stress resistance pathways, reactive oxygen species (ROS), and iron ion binding. Further study showed that the contents of O2 •-, H2O2, and malondialdehyde (MDA) were significantly increased in BG and CG tissues. Under anaerobic conditions caused by excessive soil moisture, the overproduction of ROS destroys cell membranes, simultaneously converting Fe2+ to Fe3+ and depositing it in the cell wall, which results in GRS, as evidenced by the success of the GRS induction test.

Dual-Responsive and Aggregation-Induced-Emission Probe for Selective Imaging of Infectious Urolithiasis.

Identifying infected stones is crucial due to their rapid growth and high recurrence rate. Here, the calcium-magnesium dual-responsive aggregation-induced emission (AIE)-active probe TCM-5COOH (Tricyano-methlene-pyridine-5COOH), distinctively engineered to distinguish high-threat infection calculi from metabolic stones, is presented. Upon incorporation of flexible alkyl carboxyl group, TCM-5COOH featuring five carboxyl moieties demonstrates excellent water solubility and enhanced penetration into porous infectious stones. The robust chelation of TCM-5COOH with stone surface-abundant Ca2+ and Mg2+ inhibits vibrational relaxation, thus triggering intense AIE signals. Remarkably, the resulting complex exhibits high insolubility, effectively anchoring within the porous structure of the infection calculi and offering prolonged illumination. Jobs' plot method reveals similar response characteristics for Ca2+ and Mg2+, with a 1:2 coordination number for both ions. Isothermal titration calorimetry (ITC) results demonstrate higher enthalpy change (ΔH) and lower entropy change (ΔS) for the reaction, indicating enhanced selectivity compared to TCM-4COOH lacking the alkyl carboxyl group. Synchrotron X-ray absorption fine spectroscopy (XAFS) validates TCM-5COOH's interaction with Ca2+ and Mg2+ at the microlevel. This dual-responsive probe excels in identifying infectious and metabolic calculi, compatible with endoscopic modalities and laser excitation, thereby prompting clinical visualization and diagnostic assessment.

Diversity of Parasitoid Wasps and Comparison of Sampling Strategies in Rice Fields Using Metabarcoding.

A comprehensive and precise evaluation of Arthropoda diversity in agricultural landscapes can enhance biological pest control strategies. We used Malaise traps and sweep nets to collect insects from three double-cropping paddy fields. DNA was extracted from the ethanol preservative of the Malaise traps and from tissue samples of selected parasitoid wasps. This was followed by amplification using DNA barcoding primers to prepare high-throughput sequencing libraries. We annotated a total of 4956 operational taxonomic units (OTUs), encompassing 174 genera and 32 families of parasitoid wasps. The ethanol filter method efficiently captured a wide range of information. However, the method has low resolution and may result in a reduced estimate of species abundance. Additional insect species were also identified in the parasitoid samples. This suggests that high throughput sequencing from adult parasitoid wasps can also detect host species, enabling a better understanding of host species and providing insights into food webs.

Low-Cost Photoelectric Flow Rate Sensors Based on a Flexible Planar Curved Beam Structure for Clinical Treatments.

In clinical treatments, reliable flow rate measurements ensure accurate drug delivery during infusions, precise gas delivery during artificial ventilations, etc., thereby reducing patient morbidity and mortality. However, precise flow rate sensors are costly, so medical devices with limited budgets choose cheaper but unsatisfactory flow rate measurement approaches, leading to increased medical risks. Here, a photoelectric flow rate sensor based on a flexible planar curved beam structure (FPCBS) is proposed. The FPCBS ensures low out-of-plane stiffness of the sensitive sheet and allows large deformation in the elastic range, enabling the flow rate sensor to measure the flow rate with high sensitivity over a wide range. Meanwhile, the flow rate sensor can be mass-produced using mature materials and manufacturing technology at less than $5 each. The flow rate sensors are integrated into a commercial infusion pump to measure drug infusion and a home ventilator to monitor respiration. The results are comparable to those measured by a commercial flow rate sensor, demonstrating the applicability of the sensor. Considering its proven outstanding performance at low cost, the flow rate sensor shows great potential in clinical treatment, medical diagnosis, and other medical fields.

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.

A carboxy-terminal ubiquitylation site regulates androgen receptor activity.

Degradation of unliganded androgen receptor (AR) in prostate cancer cells can be prevented by proteasome inhibition, but this is associated with only modest increases in polyubiquitylated AR. An inhibitor (VLX1570) of the deubiquitylases associated with the proteasome did not increase ubiquitylation of unliganded AR, indicating that AR is not targeted by these deubiquitylases. We then identified a series of AR ubiquitylation sites, including a not previously identified site at K911, as well as methylation sites and previously identified phosphorylation sites. Mutagenesis of K911 increases AR stability, chromatin binding, and transcriptional activity. We further found that K313, a previously reported ubiquitylation site, could also be methylated and acetylated. Mutagenesis of K313, in combination with K318, increases AR transcriptional activity, indicating that distinct posttranslational modifications at K313 differentially regulate AR activity. Together these studies expand the spectrum of AR posttranslational modifications, and indicate that the K911 site may regulate AR turnover on chromatin.

Mutational signature and prognosis in adenocarcinoma of the bladder.

Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.