An acid-chromic luminescent lanthanide metallogel for time-dependent information encryption and anti-counterfeiting.

Luminescent materials with dynamic color transformation demonstrate significant potential in advanced information encryption and anti-counterfeiting. In this study, we designed multi-color luminescent lanthanide metallogels featuring time-dependent color transformation. These materials are based on Förster resonance energy transfer (FRET) platforms, facilitating cascade energy transfer from the ligand 4,4',4''-[1,3,5-benzenetriyltris (carbonylimino)]trisbenzoic acid (H3L) to Tb3+ ions and subsequently to Sulforhodamine 101. The emission color of the gels can be readily adjusted by the introduction of HCl, transitioning from initial green, yellow, light red, and red hues to blue, violet, pink, and deep red, respectively. Importantly, the color change in these gels is time-dependent, controlled by the hydrolysis time of glucono-δ-lactone, which modulates the luminescence intensity of H3L, Tb3+, and Sulforhodamine 101. Exploiting these characteristics, we developed methods for information encryption utilizing 3D color codes and anti-counterfeiting flower patterns. These patterns undergo time-dependent transformations, generating a series of 3D codes and flower patterns that can only be recognized in a predetermined manner. These findings highlight the promising application of lanthanide metallogels in advanced information protection strategies.

Temporal Relationship-Aware Treadmill Exercise Test Analysis Network for Coronary Artery Disease Diagnosis.

The treadmill exercise test (TET) serves as a non-invasive method for the diagnosis of coronary artery disease (CAD). Despite its widespread use, TET reports are susceptible to external influences, heightening the risk of misdiagnosis and underdiagnosis. In this paper, we propose a novel automatic CAD diagnosis approach. The proposed approach introduces a customized preprocessing method to obtain clear electrocardiograms (ECGs) from individual TET reports. Additionally, it presents TETDiaNet, a novel neural network designed to explore the temporal relationships within TET ECGs. Central to TETDiaNet is the TETDia block, which mimics clinicians' diagnostic processes to extract essential diagnostic information. This block encompasses an intra-state contextual learning module and an inter-state contextual learning module, modeling the temporal relationships within a single state and between states, respectively. These two modules help the TETDia block to capture effective diagnosis information by exploring the temporal relationships within TET ECGs. Furthermore, we establish a new TET dataset named TET4CAD for CAD diagnosis. It contains simplified TET reports for 192 CAD patients and 224 non-CAD patients, and each patient undergoes coronary angiography for labeling. Experimental results on TET4CAD underscore the superior performance of the proposed approach, highlighting the discriminative value of the temporal relationships within TET ECGs for CAD diagnosis.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Efficacy and safety of first-line chemotherapies for patients with advanced pancreatic ductal adenocarcinoma: A systematic review and network meta-analysis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons of different regimens are limited. This study conducted a systematic review and network meta-analysis (NMA) to compare the efficacy and safety of various chemotherapy regimens, with the unique advantage of only including Phase III randomized controlled trials (RCTs). Methods: NMA was conducted regarding the searched phase III RCTs by comparing overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of different chemotherapy protocols. Results: The analysis included 24 studies with 11470 patients across 25 treatment modalities. Among the chemotherapy regimens evaluated, FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) demonstrated the highest OS and PFS, with a risk ratio (logHR) of 4.5 (95 % confidence interval 4.32-4.68) compared to gemcitabine monotherapy. The PEFG regimen (cisplatin, epirubicin, 5-fluorouracil, and gemcitabine) exhibited the highest ORR, with an odds ratio (OR) of 6.67 (2.08-20) compared to gemcitabine monotherapy. Notably, gemcitabine plus sorafenib was associated with the lowest hematological toxicity, with an odds ratio (OR) of 0.1 (0.02-0.48). Conclusion: Combination therapies may offer greater benefits but also cause more toxic effects. However, combinations with targeted agents seem to have fewer adverse reactions.

Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK.

BACKGROUND: Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. METHODS: We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. RESULTS: Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. CONCLUSION: Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

Reducing brain Aß burden ameliorates high-fat diet-induced fatty liver disease in APP/PS1 mice.

High-fat diet (HFD)-induced fatty liver disease is a deteriorating risk factor for Alzheimer's disease (AD). Mitigating fatty liver disease has been shown to attenuate AD-like pathology in animal models. However, it remains unclear whether enhancing Aß clearance through immunotherapy would in turn attenuate HFD-induced fatty liver or whether its efficacy would be compromised by long-term exposure to HFD. Here, the therapeutic potentials of an anti-Aß antibody, NP106, was investigated in APP/PS1 mice by HFD feeding for 44 weeks. The data demonstrate that NP106 treatment effectively reduced Aß burden and pro-inflammatory cytokines in HFD-fed APP/PS1 mice and ameliorated HFD-aggravated cognitive impairments during the final 18 weeks of the study. The rejuvenating characteristics of microglia were evident in APP/PS1 mice with NP106 treatment, namely enhanced microglial Aß phagocytosis and attenuated microglial lipid accumulation, which may explain the benefits of NP106. Surprisingly, NP106 also reduced HFD-induced hyperglycemia, fatty liver, liver fibrosis, and hepatic lipids, concomitant with modifications in the expressions of genes involved in hepatic lipogenesis and fatty acid oxidation. The data further reveal that brain Aß burden and behavioral deficits were positively correlated with the severity of fatty liver disease and fasting serum glucose levels. In conclusion, our study shows for the first time that anti-Aß immunotherapy using NP106, which alleviates AD-like disorders in APP/PS1 mice, ameliorates fatty liver disease. Minimizing AD-related pathology and symptoms may reduce the vicious interplay between central AD and peripheral fatty liver disease, thereby highlighting the importance of developing AD therapies from a systemic disease perspective.

Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions. Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns. Approach: We design a structurally constrained, pathology-aware, transformer generative adversarial network, namely structurally constrained pathology-aware convolutional transformer generative adversarial network (SCPAT-GAN), to generate virtual stained H&E histology from OCT images. We quantitatively evaluate the quality of virtual stained histology images by measuring the Fréchet inception distance (FID) and perceptual hash value (PHV). Moreover, we invite experienced pathologists to evaluate the virtual stained images. Furthermore, we visually inspect the virtual stained image generated by SCPAT-GAN. Also, we perform an ablation study to validate the design of the proposed SCPAT-GAN. Finally, we demonstrate 3D virtual stained histology images. Results: Compared to previous research, the proposed SCPAT-GAN achieves better FID and PHV scores. The visual inspection suggests that the virtual histology images generated by SCPAT-GAN resemble both normal and pathological features without artifacts. As confirmed by the pathologists, the virtual stained images have good quality compared to real histology images. The ablation study confirms the effectiveness of the combination of proposed pathological awareness and structural constraining modules. Conclusions: The proposed SCPAT-GAN is the first to demonstrate the feasibility of generating both normal and pathological patterns without pixel-wisely supervised training. We expect the SCPAT-GAN to assist in the clinical evaluation of treating the CAD by providing 2D and 3D histopathological visualizations.

[Differences of Three Methods in Determining Ozone Sensitivity in Nanjing].

In recent years， ozone （O3） has become an increasingly important air pollutant in China. Identifying the sensitivity of O3 to the precursors volatile organic compounds （VOCs） and nitrogen oxides （NOx） can help make effective abatement strategies. This study compared three methods for determining O3-VOCs-NOx sensitivity： simulated photochemical indicator values and sensitivity coefficients derived from a three-dimensional air quality model and an observation-based model （OBM）， with a case study involving an O3 pollution event that occurred in Nanjing in late July 2017. The results showed that O3 sensitivity based on the photochemical indicator and sensitivity coefficients demonstrated similar spatial variations （over 50% of the grid cells of Nanjing exhibiting identical O3 sensitivity）. However， sensitivity coefficients identified a larger number of areas within a transitional O3 sensitivity regime， as opposed to the VOCs- or NOx-limited regime identified by the photochemical indicator. The determination of the latter was affected by the adopted threshold values. The OBM relied on the quality of the observational data. For example， positive biases in observed NO2 could lead to an underestimation of O3 sensitivity to NOx with the OBM. During the high pollution period， the three methods exhibited significant disparities. The photochemical indicator tended to suggest the VOCs-limited condition， whereas the OBM and sensitivity coefficients indicated the NOx-limited or transitional regimes.

Discovery of a novel series of pyridone amides as NaV1.8 inhibitors.

The NaV1.8 channel, mainly found in the peripheral nervous system, is recognized as one of the key factors in chronic pain. The molecule VX-150 was initially promising in targeting this channel, but the phase II trials of VX-150 did not show expected pain relief results. By analyzing the interaction mode of VX-150 and NaV1.8, we developed two series with a total of 19 molecules and examined their binding affinity to NaV1.8 in vitro and analgesic effect in vivo. One compound, named 2j, stood out with notable activity against the NaV1.8 channel and showed effective pain relief in models of chronic inflammatory pain and neuropathic pain. Our research points to 2j as a strong contender for developing safer pain-relief treatments.

Identification of (4-chlorophenyl)(5-hydroxynaphtho[1,2-b]furan-3-yl)methanone as novel COX-2 inhibitor with analgesic profile.

Chronic pain is a serious problem that affects billions of people worldwide, but current analgesic drugs limit their use in chronic pain management due to their respective side effects. As a first-line clinical drug for chronic pain, COX-2 selective inhibitors can relieve mild to moderate pain, but they also have some problems. The most prominent one is that their analgesic intensity is not enough, and they cannot well meet the treatment needs of chronic pain. Therefore, there is an urgent need to develop COX-2 inhibitors with stronger analgesic intensity. In this article, we used virtual screening method to screen out the structurally novel COX-2 inhibitor for chronic pain management, and conducted a preliminary study on its mechanism of action using molecular dynamics simulation.

Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of Survivin.

Human malignancies exhibit elevated levels of survivin, and have been linked to poor prognosis. Targeting survivin expression is a promising therapeutic strategy against cancer cells. Natural compounds have become a hot topic in research due to their non-toxic, non-invasive, and efficient treatment of multiple diseases. In this current investigation, it was discovered that Dioscin, as a natural compound, exerted profound antitumor activity against NSCLC cell lines, inhibiting NSCLC cell viability and promoting apoptosis. Further mechanistic studies showed that Dioscin promoted ubiquitination-mediated survivin degradation via strengthening the interaction between survivin and the E3 ubiquitin ligase Fbxl7. Furthermore, Dioscin exhibited a strong tumor suppressive effect in xenograft tumor models, and Dioscin treatment led to a notable decrease in tumor volume and weight. Based on our findings, Dioscin is expected to be a potential antitumor agent for non-small cell lung cancer treatment.

Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image.

Denoising is a necessary step in image analysis to extract weak signals, especially those hardly identified by the naked eye. Unlike the data-driven deep-learning denoising algorithms relying on a clean image as the reference, Noise2Noise (N2N) was able to denoise the noise image, providing sufficiently noise images with the same subject but randomly distributed noise. Further, by introducing data augmentation to create a big data set and regularization to prevent model overfitting, zero-shot N2N-based denoising was proposed in which only a single noisy image was needed. Although various N2N-based denoising algorithms have been developed with high performance, their complicated black box operation prevented the lightweight. Therefore, to reveal the working function of the zero-shot N2N-based algorithm, we proposed a lightweight Peak2Peak algorithm (P2P) and qualitatively and quantitatively analyzed its denoising behavior on the 1D spectrum and 2D image. We found that the high-performance denoising originates from the trade-off balance between the loss function and regularization in the denoising module, where regularization is the switch of denoising. Meanwhile, the signal extraction is mainly from the self-supervised characteristic learning in the data augmentation module. Further, the lightweight P2P improved the denoising speed by at least ten times but with little performance loss, compared with that of the current N2N-based algorithms. In general, the visualization of P2P provides a reference for revealing the working function of zero-shot N2N-based algorithms, which would pave the way for the application of these algorithms toward real-time (in situ, in vivo, and operando) research improving both temporal and spatial resolutions. The P2P is open-source at https://github.com/3331822w/Peak2Peakand will be accessible online access at https://ramancloud.xmu.edu.cn/tutorial.

APOB is a potential prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is significantly associated with adverse prognostic outcomes. The development and progression of different types of human tumors are significantly influenced by APOB. Nevertheless, the significance and pathomechanisms of APOB in HCC have not been conclusively determined. We assessed APOB expression levels in HCC using three publicly available databases of TIMER2.0, UALCAN and Human Protein Atlas. To identify the biological function of APOB, we conducted enrichment analysis via LinkedOmics. Moreover, UALCAN was employed to assess the relationship between APOB expression and clinicopathological features among HCC patients. Additionally, the Kaplan-Meier plotter was utilized to investigate the prognostic relevance of APOB in HCC. To explore potential regulatory ncRNAs that could bind to APOB, we utilized StarBase and GEPIA. Furthermore, the correlation between APOB expression and immune cell infiltration, as well as immune checkpoint genes, was investigated using Spearman's correlation analysis in TISIDB, GEPIA, and TIMER2.0. The findings of our investigation showed a notable decrease in the expression levels of APOB among individuals diagnosed with HCC. Moreover, a noteworthy correlation was observed between the expression of APOB and immune checkpoint genes, alongside the occurrence of immune cell infiltration. The levels of APOB expression in HCC tissues also showed correlations with various clinicopathological features. According to Cox regression analysis, decreased APOB expression emerged as a potential autonomous predictor for OS, RFS, DSS, and PFS among HCC patients. Furthermore, we identified six potential pathways associated with non-coding RNA (ncRNA) as the most promising pathway for APOB in HCC. Our results illuminate the possible involvement of APOB in HCC and offer understanding into its governing mechanisms and medical importance.

Androgen-repressed lncRNA LINC01126 drives castration-resistant prostate cancer by regulating the switch between O-GlcNAcylation and phosphorylation of androgen receptor.

BACKGROUND: Prostate cancer (PCa) initially shows satisfactory response to therapies targeting the androgen receptor (AR). However, progression to a castration-resistant stage indicates poor prognosis in PCa patients. AR signalling still plays a central role in most castration-resistant prostate cancers (CRPC). Therefore, unveiling the mechanisms of AR reactivation under androgen-deprived conditions is imperative to discover novel therapeutic targets for CRPC. METHODS: Using an integrative analysis of the transcriptomics of three independent PCa cohorts and a published landscape of AR-regulated long non-coding RNA (lncRNA), lncRNA LINC01126 was selected as a candidate gene that could drive CRPC progression for further study. Quantitative reverse transcription polymerase chain reaction, in situ hybridisation (ISH) and fluorescent ISH were performed to detect LINC01126 in PCa tissues and cells. The functional role and mechanism of LINC01126 were further investigated using in vitro and in vivo gain and loss of function assays. RESULTS: LINC01126, identified as an AR-repressed lncRNA, was significantly upregulated after AR-targeted therapies. In addition, we found that LINC01126 was upregulated in CRPC and was associated with poor prognosis. We also proved that LINC01126 stabilised AR protein and enhanced AR nuclear translocation and transactivation by promoting the transition from O-GlcNAcylation at threonine 80 to phosphorylation at serine 81 (S81) within the AR protein. Mechanism analysis revealed that LINC01126 facilitates the interaction of CDK9 with AR and impedes the binding of O-linked N-acetylglucosamine (O-GlcNAc) transferase to AR. Consequently, LINC01126 expression was sufficient to activate AR signalling without androgen. LINC01126 overexpression increased, whereas LINC01126 knockdown decreased castration resistance traits in PCa cells in vitro and in vivo. Furthermore, our data showed that LINC01126-targeting antisense oligonucleotides (ASO) substantially inhibited CRPC cells in vitro. CONCLUSIONS: Our research expands the functions of AR-regulated lncRNA in sustaining androgen-independent AR activity and promoting CRPC progression and reveals that LINC01126 may be a new therapeutic target for PCa.

TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.

Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. Despite continuous improvement in treatment strategies, recurrence or persistence of cancer after radiotherapy is still inevitable, highlighting the need to identify therapeutic resistance factors and develop effective methods for NPC treatment. Herein, we found that TRAF4 is overexpressed in NPC cells and tissues. Knockdown TRAF4 significantly increased the radiosensitivity of NPC cells, possibly by inhibiting the Akt/Wee1/CDK1 axis, thereby suppressing survivin phosphorylation and promoting its degradation by FBXL7. TRAF4 is positively correlated with p-Akt and survivin in NPC tissues. High protein levels of TRAF4 were observed in acquired radioresistant NPC cells, and knockdown of TRAF4 overcomes radioresistant in vitro and the xenograft mouse model. Altogether, our study highlights the TRAF4-survivin axis as a potential therapeutic target for radiosensitization in NPC.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

TurboID-mediated proximity labeling for screening interacting proteins of FIP37 in Arabidopsis.

Proximity labeling was recently developed to detect protein-protein interactions and members of subcellular multiprotein structures in living cells. Proximity labeling is conducted by fusing an engineered enzyme with catalytic activity, such as biotin ligase, to a protein of interest (bait protein) to biotinylate adjacent proteins. The biotinylated protein can be purified by streptavidin beads, and identified by mass spectrometry (MS). TurboID is an engineered biotin ligase with high catalytic efficiency, which is used for proximity labeling. Although TurboID-based proximity labeling technology has been successfully established in mammals, its application in plant systems is limited. Here, we report the usage of TurboID for proximity labeling of FIP37, a core member of m6A methyltransferase complex, to identify FIP37 interacting proteins in Arabidopsis thaliana. By analyzing the MS data, we found 214 proteins biotinylated by GFP-TurboID-FIP37 fusion, including five components of m6A methyltransferase complex that have been previously confirmed. Therefore, the identified proteins may include potential proteins directly involved in the m6A pathway or functionally related to m6A-coupled mRNA processing due to spatial proximity. Moreover, we demonstrated the feasibility of proximity labeling technology in plant epitranscriptomics study, thereby expanding the application of this technology to more subjects of plant research.

Indocyanine Green Fluorescence Imaging in the Surgical Management of Skin Squamous Cell Carcinoma.

Introduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC). Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision. Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified. Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.

High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

BACKGROUND: Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis, which were linked with discordant FDG positivity and low Prostate-Specific Membrane Antigen (PSMA) expression. A recent study only cited a DAC patient with low 68Ga-PSMA-11 PET/CT uptake but high 18F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients. METHODS: The study was conducted on 87 DAC or/and IDC-P patients without any treatment and 97 PAC patients with a Gleason score ≥8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1. RESULTS: PSMA expression in PAC was significantly higher than in DAC/IDC-P (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA expression between DAC/IDC-P and adjacent PAC (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P than in adjacent PAC (68.6 vs 51.3, p = 0.007), but was still lower than that in pure PAC (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in pure PAC (13.0 vs 6.6, p = 0.025), and in PAC adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001). CONCLUSIONS: In DAC/IDC-P tissues, PSMA expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC/IDC-P may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism.