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.

Tunable Surface Charge of Layered Double Hydroxide Membranes Enabling Osmotic Energy Harvesting from Anion Transport.

Membrane-based osmotic energy harvesting is a promising technology with zero carbon footprint. High-performance ion-selective membranes (ISMs) are the core components in such applications. Recent advancement in 2D nanomaterials opens new avenues for building highly efficient ISMs. However, the majority of the explored 2D nanomaterials have a negative surface charge, which selectively enhances cation transport, resulting in the underutilization of half of the available ions. In this study, ISMs based on layered double hydroxide (LDH) with tunable positive surface charge are studied. The membranes preferentially facilitate anion transport with high selectivity. Osmotic energy harvesting device based on these membranes reached a power density of 2.31 W m-2 under simulated river/sea water, about eight times versus that of a commercial membrane tested under the same conditions, and up to 7.05 W m-2 under elevated temperature and simulated brine/sea water, and long-term stability with consistent performance over a 40-day period. A prototype reverse electrodialysis energy harvesting device, comprising a pair of LDH membranes and commercial cation-selective membranes, is able to simultaneously harvest energy from both cations and anions achieving a power density of 6.38 W m-2 in simulated river/sea water, demonstrating its potential as building blocks for future energy harvesting systems.

Accurate Temperature Reconstruction in Radiofrequency Ablation for Atherosclerotic Plaques Based on Inverse Heat Transfer Analysis.

Radio frequency ablation has emerged as a widely accepted treatment for atherosclerotic plaques. However, monitoring the temperature field distribution in the blood vessel wall during this procedure presents challenges. This limitation increases the risk of endothelial cell damage and inflammatory responses, potentially leading to lumen restenosis. The aim of this study is to accurately reconstruct the transient temperature distribution by solving a stochastic heat transfer model with uncertain parameters using an inverse heat transfer algorithm and temperature measurement data. The nonlinear least squares optimization method, Levenberg-Marquardt (LM), was employed to solve the inverse heat transfer problem for parameter estimation. Then, to improve the convergence of the algorithm and reduce the computational resources, a method of parameter sensitivity analysis was proposed to select parameters mainly affecting the temperature field. Furthermore, the robustness and accuracy of the algorithm were verified by introducing random noise to the temperature measurements. Despite the high level of temperature measurement noise (ξ = 5%) and larger initial guess deviation, the parameter estimation results remained closely aligned with the actual values, with an overall ERMS consistently below 0.05. The absolute errors between the reconstruction temperature at the measurement points TC1, TC2, and TC3, and the actual temperature, remained within 0.33 °C, 2.4 °C, and 1.17 °C, respectively. The Levenberg-Marquardt algorithm employed in this study proficiently tackled the ill-posed issue of inversion process and obtained a strong consistency between the reconstructed temperature the actual temperature.

Improved Photo-Excited Carriers Transportation of WS2 -O-Doped-Graphene Heterostructures for Solar Steam Generation.

Two-dimensional (2D) transition metal dichalcogenides and graphene have revealed promising applications in optoelectronic and energy storage and conversion. However, there are rare reports of modifying the light-to-heat transformation via preparing their heterostructures for solar steam generation. In this work, commercial WS2 and sucrose are utilized as precursors to produce 2D WS2 -O-doped-graphene heterostructures (WS2 -O-graphene) for solar water evaporation. The WS2 -O-graphene evaporators demonstrate excellent average water evaporation rate (2.11 kg m-2  h-1 ) and energy efficiency (82.2%), which are 1.3- and 1.2-fold higher than WS2 and O-doped graphene-based evaporators, respectively. Furthermore, for the real seawater with different pH values (pH 1 and 12) and rhodamine B pollutants, the WS2 -O-graphene evaporators show great average evaporation rates (≈2.08 and 2.09 kg m-2  h-1 , respectively) for producing freshwater with an extremely low-grade of dye residual and nearly neutral pH values. More interestingly, due to the self-storage water ability of WS2 -O-graphene evaporators, water evaporation can be implemented without the presence of bulk water. As a result, the evaporation rate reaches 3.23 kg m-2  h-1 , which is ≈1.5 times higher than the regular solar water evaporation system. This work provides a new approach for preparing 2D transition metal dichalcogenides and graphene heterostructures for efficient solar water evaporation.

Investigation of Rapid Rewarming Chips for Cryopreservation by Joule Heating.

Rapid and uniform rewarming is critical to cryopreservation. Current rapid rewarming methods require complex physical field application devices (such as lasers or radio frequencies) and the addition of nanoparticles as heating media. These complex devices and nanoparticles limit the promotion of the rapid rewarming method and pose potential biosafety concerns. In this work, a joule heating-based rapid electric heating chip (EHC) was designed for cryopreservation. Uniform and rapid rewarming of biological samples in different volumes can be achieved through simple operations. EHC loaded with 0.28 mL of CPA solution can achieve a rewarming rate of 3.2 × 105 °C/min (2.8 mL with 2.3 × 103 °C/min), approximately 2 orders of magnitude greater than the rewarming rates observed with an equal capacity straw when combined with laser nanowarming or magnetic induction heating. In addition, the degree of supercooling can be significantly reduced without manual nucleation during the cooling of the EHC. Subsequently, the results of cryopreservation validation of cells and spheroids showed that the cell viability and spheroid structural integrity were significantly improved after cryopreservation. The viability of human lung adenocarcinoma (A549) cells postcryopreservation was 97.2%, which was significantly higher than 93% in the cryogenic vials (CV) group. Similar results were seen in human mesenchymal stem cells (MSCs), with 93.18% cell survival in the EHC group, significantly higher than 86.83% in the CV group, and cells in the EHC group were also significantly better than those in the CV group for further apoptosis and necrosis assays. This work provides an efficient rewarming protocol for the cryopreservation of biological samples, significantly improving the quantity and quality of cells and spheroids postcryopreservation.

Histopathological observation and comparative transcriptome analysis reveal immune response mechanisms to Aeromonas dhakensis infection in Macrobrachium rosenbergii.

The Macrobrachium rosenbergii industry is threatened by various Aeromonas, resulting in high mortality of adult prawns. However, there are few studies on the immune response of M. rosenbergii infected with Aeromonas dhakensis. In this study, we observed the hepatopancreas and gills histopathologically, performed a comparative transcriptome analysis of the hepatopancreas, and analyzed the candidate gene expression of immune-related genes in the hemolymph, hepatopancreas, and gills of M. rosenbergii that had been infected with A. dhakensis. Histopathology revealed the hepatopancreas was successively inflamed, followed by cellular vacuolation, lumen deformation, and finally tissue erosion; partial and severe inflammation of the gills occurred successively, and eventually the gill tissue atrophy and the gill filaments detached from the gill arch. Transcriptome analysis showed that a total of 77,742 unigenes and 8664 differentially expressed genes (DEGs), and the immune-related DEGs were mainly enriched in lysosome and phagosome pathways. In addition, 4 immune-related candidate genes (RhoA, CASP9, PKC, and DSCIGN) based on KEGG and PPI analysis were monitored at 6, 12, and 24h post injection (hpi) in hepatopancreas, hemolymph and gills. Their spatio-temporal expression results indicated that A. dhakensis have activated the immune system of M. rosenbergii. The present study may provide new information on the complex immune mechanism of M. rosenbergii.

Structural design optimization and lipolytic effect prediction of vacuum suction cryolipolysis applicator: Simulation study.

BACKGROUND AND OBJECTIVES: Cryolipolysis is a popular noninvasive lipolytic method that uses low temperature to induce apoptosis or necrosis of adipocytes to reduce local fat in the human body. Vacuum suction applicator is a commonly used cryolipolysis equipment, which suction human skin and fat into a chamber for cooling. The structure of vacuum suction applicator is usually irregular, its cooling characteristic is also complex, and unreasonable suction structure will cause human discomfort. Biological experiments and clinical studies are often used to study the structural design of applicators, whereas these methods are impossible to obtain the three-dimensional cooling characteristic of applicator comprehensively and require a lot of costs. This study aims to optimize the structure of applicator for lowering discomfort, evaluate the cooling characteristic and lipolytic effect of applicators, which could provide guidance for clinical application of applicators and reduce costs. MATERIALS AND METHODS: Cryolipolysis applicators models with four vacuum suction angles were established, and COMSOL was used to compare the cooling performance parameters, cooling kinetics, and lipolytic effects of the applicators. Specific evaluation indicators also include: cooling capacity analysis, temperature field analysis, lipolytic percentage, lipolytic volume, lipolytic weight, lipolytic thickness, lipolytic waistline, and lipolysis temperature threshold analysis. RESULTS: The applicator with a small suction angle has a greater cooling capacity to cool deeper level of fat. When the cooling temperature is -10°C, the temperature of skin layer is about -10°C at 60 minutes, the temperature of fat layer is -7.36 to 3.01°C at 10 mm, -3.67 to 5.91°C at 20 mm and 2.01-10.81°C at 30 mm. The percentage of lipolytic declined with the increase of suction angle, the final lipolytic percentage (35.81%) of the 90° applicator is the highest, the percentage (28.72%) of 150° applicator (28.72%) is the lowest. The lipolytic volume, weight, and average thickness of applicator constantly increased with the increase of the suction angle, the final lipolytic volume range of the four suction angle applicators is 171.88-310.18 cm3 , the lipolytic weight range is 160.11-288.93 g, and the lipolytic average thickness range is 1.21-1.36 cm. Lower lipolysis temperature threshold will reduce the lipolysis effect, but it may also lead to another lipolysis mechanism-cell necrosis. CONCLUSION: Different suction angles significantly affect the cooling characteristics and lipolytic effects of cryolipolysis applicator. A reasonable suction angle is one of the critical factors to improve the efficiency and comfort of cryolipolysis.

An Experimental Study: Treatment of Subcutaneous C6 Glioma in Rats Using Acoustic Droplet Vaporization.

OBJECTIVE: The objective of this study was to investigate the treatment effects of acoustic droplet vaporization (ADV) on tumors. METHODS: Experiments were conducted on subcutaneous C6 glioma implanted in 37 rats. Twenty-five rats were divided into five groups treated by ultrasound (US) + dodecafluoropentane (DDFP), US + microbubble (MB), US, DDFP, or saline, respectively. ADV was performed using DDFP droplets (2-5 µm) triggered by non-focused pulsed ultrasound. Macroscopic and histological changes of the tumor were compared with investigation of the tumor ablation effect of ADV. Tumor temperature was measured before and immediately after treatment to explore temperature changes. Furthermore, another 12 rats with bilateral tumors were divided into two groups. Six animals received ADV treatment on unilateral tumor, while another six received saline injection on unilateral tumor. The tumor blood perfusion, tumor volume and related immune response were measured. RESULTS: The tumors treated by ADV were partially damaged without significant temperature rise. For the animals with bilateral tumors, the tumor blood perfusion around the damaged area on the side receiving ADV still existed. Additionally, the bilateral tumors of animals treated with ADV were smaller than those of animals treated with saline, along with stronger immune response and more tumor cell apoptosis in tumors on both sides. CONCLUSION: The study demonstrated that ADV treatment could damage subcutaneous glioma in rats by mechanical effect and enhance systemic immune response to furtherly inhibit the tumor growth.

A Multi-Scale Dehazing Network with Dark Channel Priors.

Image dehazing based on convolutional neural networks has achieved significant success; however, there are still some problems, such as incomplete dehazing, color deviation, and loss of detailed information. To address these issues, in this study, we propose a multi-scale dehazing network with dark channel priors (MSDN-DCP). First, we introduce a feature extraction module (FEM), which effectively enhances the ability of feature extraction and correlation through a two-branch residual structure. Second, a feature fusion module (FFM) is devised to combine multi-scale features adaptively at different stages. Finally, we propose a dark channel refinement module (DCRM) that implements the dark channel prior theory to guide the network in learning the features of the hazy region, ultimately refining the feature map that the network extracted. We conduct experiments using the Haze4K dataset, and the achieved results include a peak signal-to-noise ratio of 29.57 dB and a structural similarity of 98.1%. The experimental results show that the MSDN-DCP can achieve superior dehazing compared to other algorithms in terms of objective metrics and visual perception.

Boosting Osmotic Energy Conversion of Graphene Oxide Membranes via Self-Exfoliation Behavior in Nano-Confinement Spaces.

Introducing alien intercalations to sub-nanometer scale nanochannels is one desirable strategy to optimize the ion transportation of two-dimensional nanomaterial membranes for improving osmotic energy harvest (OEH). Diverse intercalating agents have been previously utilized to realize this goal in OEH, but with modest performance, complex operations, and physicochemical uncertainty gain. Here, we employ the self-exfoliation behavior of oxidative fragments (OFs) from graphene oxide basal plane under an alkaline environment to encapsulate detached OFs in nanochannels for breaking a trade-off between permeability and selectivity, boosting power density from 1.8 to 4.9 W m-2 with a cation selectivity of 0.9 and revealing a negligible decline in power density and trade-off during a long-term operation test (∼168 h). The strategy of membrane design, employing the intrinsically self-exfoliated OFs to decorate the nanochannels, provides an alternative and facile approach for ion separation, OEH, and other nano-fluidic applications.

2D Higher-Metal Nitride Nanosheets for Solar Steam Generation.

Higher-metal (HM) nitrides are a fascinating family of materials being increasingly researched due to their unique physical and chemical properties. However, few focus on investigating their application in a solar steam generation because the controllable and large-scale synthesis of these materials remains a significant challenge. Herein, it is reported that higher-metal molybdenum nitride nanosheets (HM-Mo5 N6 ) can be produced at the gram-scale using amine-functionalized MoS2 as precursor. The first-principles calculation confirms amine-functionalized MoS2 nanosheet effectively lengthens the bonds of MoS leading to a lower bond binding energy, promoting the formation of MoN bonds and production of HM-Mo5 N6 . Using this strategy, other HM nitride nanosheets, such as W2 N3 , Ta3 N5 , and Nb4 N5 , can also be synthesized. Specifically, under one simulated sunlight irradiation (1 kW m-2 ), the HM-Mo5 N6 nanosheets are heated to 80 °C within only ≈24 s (0.4 min), which is around 78 s faster than the MoS2 samples (102 s/1.7 min). More importantly, HM-Mo5 N6 nanosheets exhibit excellent solar evaporation rate (2.48 kg m-2  h-1 ) and efficiency (114.6%), which are 1.5 times higher than the solar devices of MoS2 /MF.

New Cryoprotectant Loading Method for Cell Droplet Vitrification with Continuous Evaporation.

Droplet-based vitrification is considered to be a promising cryopreservation method, which achieves high cell viability through high cooling rates and low concentrations of cryoprotective agents (CPAs). However, the droplet vitrification cryopreservation process needs in-depth research, such as the balance of the CPA concentration and the cooling rate, the CPA loading process, and the droplet encapsulation method. Here, we developed a chip with a high cooling rate for vitrification droplet encapsulation and provided a new method for continuous loading of low-concentration CPA droplets by evaporation. The results showed that the CPA droplet volume decreased exponentially with the evaporation time, and the larger the initial droplet size, the longer the evaporation time to achieve the critical vitrification concentration. There was no significant difference in the viability of MSCs, NHEK, and A549 cells between the evaporation loading vitrification method and the traditional slow freezing method, but the former was easier to operate and can balance the cooling rate and concentration by controlling the evaporation time. Moreover, a theoretical model was proposed to predict the CPA concentration inside the microdroplets dependent on the evaporation time. The current work provides a potential method to load low-concentration CPAs for cell vitrification preservation, which is more beneficial for cell therapy and other regenerative medicine applications.

Enhanced Ion Sieving of Graphene Oxide Membranes via Surface Amine Functionalization.

Membranes based on two-dimensional (2D) nanomaterials have shown great potential to alleviate the worldwide freshwater crisis due to their outstanding performance of freshwater extraction from saline water via ion rejection. However, it is still very challenging to achieve high selectivity and high permeance of water desalination through precise d-spacing control of 2D nanomaterial membranes within subnanometer. Here, we developed functionalized graphene oxide membranes (FGOMs) with nitrogen groups such as amine groups and polarized nitrogen atoms to enhance metal ion sieving by one-step controlled plasma processing. The nitrogen functionalities can produce strong electrostatic interactions with metal ions and result in a mono/divalent cation selectivity of FGOMs up to 90 and 28.3 in single and binary solution, which is over 10-fold than that of graphene oxide membranes (GOMs). First-principles calculation confirms that the ionic selectivity of FGOMs is induced by the difference of binding energies between metal ions and polarized nitrogen atoms. Besides, the ultrathin FGOMs with a thickness of 50 nm can possess a high water flux of up to 120 mol m-2 h-1 without sacrificing rejection rates of nearly 99.0% on NaCl solution, showing an ultrahigh water/salt selectivity of around 4.31 × 103. Such facile and efficient plasma processing not only endows the GOMs with a promising future sustainable water purification, including ion separation and water desalination, but also provides a new strategy to functionalize 2D nanomaterial membranes for specific purposes.

Single-cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer.

Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.

Mutational and transcriptomic landscapes of a rare human prostate basal cell carcinoma.

BACKGROUND: As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. METHODS: Here, we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34ßE12+ /P63+ /PAP- /PSA- ). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained. RESULTS: The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells. CONCLUSIONS: This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.

Investigating industrial water-use efficiency in mainland China: An improved SBM-DEA model.

Improving water-use efficiency (WUE) is a crucial way of achieving green industrial production and sustainable development. Applying an improved Super-slacks-based measure model with undesirable outputs, this paper investigates industrial WUE in mainland China. The results show that: (1) Industrial WUE in China is improving with the efficiency value increasing from 0.9874 to 0.9962 in 2012-2015. (2) The regions of water absolute scarcity and the vulnerability show the highest industry-related WUE, whereas the water stressed region, water scarce region, and water abundant region failed to achieve efficiency during the observation period. (3) The overall index value using the conventional model was higher than that of the improved model, indicating the need for a more reasonable water-use structure and environmentally friendly discharge structure. This study provides a new perspective for measuring industrial WUE and advances related studies by (1) incorporating the actual structure of water used and wastewater discharged with weights assigned to input and output slacks according to marginal use cost of water and marginal treatment cost of wastewater; and (2) adding realistic constraints on the amount of water used and wastewater discharged to the model. The estimated provinces in mainland China can adjust their industrial water-use structures and wastewater-discharge structures based on the results of this study, and thus improve the industrial WUE.

NIR-Triggered Multifunctional and Degradable Nanoplatform Based on an ROS-Sensitive Block Copolymer for Imaging-Guided Chemo-Phototherapy.

Imaging-guided chemo-phototherapy based on multifunctional nanocarriers has emerged as a promising and high-efficient cancer treatment because of the inevitable limitations of single therapy. Herein, a near-infrared (NIR) light-activated degradable polymeric nanoplatform was fabricated for chemo-phototherapy. An NIR photosensitizer, IR780, and a chemotherapeutic drug, doxorubicin (DOX), were efficiently coloaded within a reactive oxygen species (ROS)-sensitive polymeric micelle based on an amphiphilic copolymer with degradable thioketal (TK) linkages. The obtained spherical nanoparticles (denoted as (IR780/DOX)@PTK) exhibited a notable photodynamic and photothermal effect upon NIR light exposure. Furthermore, due to the rapid cleavage of TK linkers induced by ROS generated from NIR-activated IR780, (IR780/DOX)@PTK also showed an NIR light-induced degradable feature, which can be used for light-triggered tumor-specific drug release and lead to ignorable systematic toxicity after biodegradation and drug delivery. Under the guidance of NIR fluorescence and photothermal dual modal imaging, (IR780/DOX)@PTK exhibited excellent tumor accumulation after intravenously injection into 4T1-tumor-bearing mice. As verified in both in vitro and in vivo study, (IR780/DOX)@PTK presented a significant tumor suppression effect by synergistic chemo-phototherapy.

Sensitization of Hypoxic Tumor to Photodynamic Therapy via Oxygen Self-Supply of Fluorinated Photosensitizers.

Photodynamic therapy (PDT) utilizes photosensitizers to convert innoxious oxygen to cytotoxic reactive oxygen species under an appropriate light, thus inducing cancer cells necrosis. However, PDT performs in an oxygen-dependent method to destroy cells while hypoxia is a feature for most solid tumors. To effectively improve the PDT effect against solid tumors, an oxygen self-supplying and pH-sensitive therapeutic nanoparticle (PTFC) has been developed by the self-assembly of a tetrakis(pentafluorophenyl) chlorin (TFPC)-conjugated block copolymer (POEGMA-b-P(DEAEMA-co-GMA)). PTFC nanoparticles can transport oxygen to a tumor site with their accumulation in the tumor on account of the good oxygen solubility, therefore relieving the oxygen deficiency of a solid tumor and enhancing the PDT efficacy. It is worth noting that the oxygen loading was realized by the fluorinated photosensitizer itself. In addition, the phototoxicity of PTFC nanoparticles is greatly improved in an acidic aqueous environment due to the DEAEMA unit protonation, which not only enhanced the cellular uptake of nanoparticles but also weakened the aggregation of photosensitizers. Taking the hypoxia and acidic microenvironment of solid tumors, PTFC nanoparticles could be efficiently taken up and disassembled to release oxygen upon accumulation at tumor sites, thus significantly improving the PDT efficacy against solid tumors.

CD163+ macrophages predict a poor prognosis in patients with primary T1 high-grade urothelial carcinoma of the bladder.

PURPOSE: Macrophages are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study investigates the prognostic value of tumor-infiltrated CD163+ macrophages in patients with T1 high-grade (T1HG) bladder cancer. METHODS: CD163+ macrophages were assessed by immunohistochemistry in 94 T1HG bladder cancer samples. Kaplan-Meier analyses and Cox proportional hazards' regression models were applied to evaluate recurrence-free survival, progression-free survival and disease-specific survival. RESULTS: With a median follow-up of 60 months, 37 (39.4%) patients experienced disease recurrence, 14 (14.9%) progression, 11 (11.7%) disease-specific mortality. High CD163+ macrophages were associated with higher risk of disease recurrence and progression (P < 0.05, for both). In multivariate Cox proportional hazards regression analysis, high CD163+ macrophages were a significant negative predictor of recurrence-free survival, progression-free survival and disease-specific survival (P < 0.05 for all). CONCLUSION: CD163+ macrophages are a poor prognostic factor in T1HG bladder cancer. This finding provide the ground for further testing it in predicting the outcome of this challenging disease.