Unveiling Novel Double-Negative Prostate Cancer Subtypes Through Single-Cell RNA Sequencing Analysis.

Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into disease heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising both publicly available cohorts and data generated by our research team, and established the HuPSA (Human Prostate Single cell Atlas) and the MoPSA (Mouse Prostate Single cell Atlas) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression, and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features. Furthermore, HuPSA-based deconvolution allowed for the re-classification of human PCa specimens, validating the presence of these novel subtypes. Leveraging these findings, we developed a user-friendly web application, "HuPSA-MoPSA" (https://pcatools.shinyapps.io/HuPSA-MoPSA/), for visualizing gene expression across all newly-established datasets. Our study provides comprehensive tools for PCa research and uncovers novel cancer subtypes that can inform clinical diagnosis and treatment strategies.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Background: Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. The expression pattern of PKM1 and PKM2 in NEPCa remains unknown. Methods: In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatics analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues. Results: We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in murine NEPCa. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of prostate adenocarcinoma (AdPCa) specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. Discussion: Our study characterized the expression pattern of PKM1 and PKM2 in prostatic tissues including developing, benign, and cancerous prostate. These findings lay the groundwork for understanding the metabolic changes in different PCa subtypes.

Organic Cocrystal Alloys: From Three Primary Colors to Continuously Tunable Emission and Applications on Optical Waveguides and Displays.

Multicolor luminescence of organic fluorescent materials is an essential part of lighting and optical communication. However, the conventional construction of a multicolor luminescence system based on integrating multiple organic fluorescent materials of a single emission band remains complicated and to be improved. Herein, organic alloys (OAs) capable of full-color emission are synthesized based on charge transfer (CT) cocrystals. By adjusting the molar ratio of electron donors, the emission color of the OAs can be conveniently and continuously regulated in a wide visible range from blue (CIE: 0.187, 0.277), to green (CIE: 0.301, 0.550), and to red (CIE: 0.561, 0.435). The OAs show analogous 1D morphology with smooth surface, allowing for full-color waveguides with low optical-loss coefficient. Impressively, full-color optical displays are easily achieved through the OAs system with continuous emission, which shows promising applications in the field of optical display and promotes the development of organic photonics.

Visualizing the interfacial-layer-based epitaxial growth process toward organic core-shell architectures.

Organic heterostructures (OHTs) with the desired geometry organization on micro/nanoscale have undergone rapid progress in nanoscience and nanotechnology. However, it is a significant challenge to elucidate the epitaxial-growth process for various OHTs composed of organic units with a lattice mismatching ratio of > 3%, which is unimaginable for inorganic heterostructures. Herein, we have demonstrated a vivid visualization of the morphology evolution of epitaxial-growth based on a doped interfacial-layer, which facilitates the comprehensive understanding of the hierarchical self-assembly of core-shell OHT with precise spatial configuration. Significantly, the barcoded OHT with periodic shells obviously illustrate the shell epitaxial-growth from tips to center parts along the seeded rods for forming the core-shell OHT. Furthermore, the diameter, length, and number of periodic shells were modulated by finely tuning the stoichiometric ratio, crystalline time, and temperature, respectively. This epitaxial-growth process could be generalized to organic systems with facile chemical/structural compatibility for forming the desired OHTs.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer. However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. PKM2 is known to be upregulated in various cancers, including prostate adenocarcinoma (AdPCa). In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatic analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues, including developing, benign and cancerous prostate. We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in some NEPCa samples. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of PCa specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. These findings lay the groundwork for understanding PKMs' role in PCa carcinogenesis and NEPCa progression. The distinct expression pattern of PKM isoforms in different PCa subtypes may offer insights into potential therapeutic strategies for treating PCa.

Precise Synthesis of Organic Cocrystal Alloys with Full-Spectrum Emission Characteristics for the Stepless Color Changing Display.

Organic luminescent materials are indispensable in optoelectronic displays and solid-state luminescence applications. Compared with single-component, multi-component crystalline materials can improve optoelectronic characteristics. This work forms a series of full-spectrum tunable luminescent charge-transfer (CT) cocrystals ranging from 400 to 800 nm through intermolecular collaborative self-assembly. What is even more interesting is that o-TCP-Cor(x)-Pe(1-x), p-TCP-Cor(x)-Pe(1-x), and o-TCP-AN(x)-TP(1-x) alloys are prepared based on cocrystals by doping strategies, which correspondingly achieve the stepless color change from blue (CIE [0.22, 0.44]) to green (CIE [0.16, 0.14]), from green (CIE [0.27, 0.56]) to orange (CIE [0.58, 0.42]), from yellow (CIE [0.40, 0.57]) to red (CIE [0.65, 0.35]). The work provides an efficient method for precisely synthesizing new luminescent organic semiconductor materials and lays a solid foundation for developing advanced organic solid-state displays.

Synaptic transistor with multiple biological functions based on metal-organic frameworks combined with the LIF model of a spiking neural network to recognize temporal information.

Spiking neural networks (SNNs) have immense potential due to their utilization of synaptic plasticity and ability to take advantage of temporal correlation and low power consumption. The leaky integration and firing (LIF) model and spike-timing-dependent plasticity (STDP) are the fundamental components of SNNs. Here, a neural device is first demonstrated by zeolitic imidazolate frameworks (ZIFs) as an essential part of the synaptic transistor to simulate SNNs. Significantly, three kinds of typical functions between neurons, the memory function achieved through the hippocampus, synaptic weight regulation and membrane potential triggered by ion migration, are effectively described through short-term memory/long-term memory (STM/LTM), long-term depression/long-term potentiation (LTD/LTP) and LIF, respectively. Furthermore, the update rule of iteration weight in the backpropagation based on the time interval between presynaptic and postsynaptic pulses is extracted and fitted from the STDP. In addition, the postsynaptic currents of the channel directly connect to the very large scale integration (VLSI) implementation of the LIF mode that can convert high-frequency information into spare pulses based on the threshold of membrane potential. The leaky integrator block, firing/detector block and frequency adaptation block instantaneously release the accumulated voltage to form pulses. Finally, we recode the steady-state visual evoked potentials (SSVEPs) belonging to the electroencephalogram (EEG) with filter characteristics of LIF. SNNs deeply fused by synaptic transistors are designed to recognize the 40 different frequencies of EEG and improve accuracy to 95.1%. This work represents an advanced contribution to brain-like chips and promotes the systematization and diversification of artificial intelligence.

A novel non-contact heart rate measurement method based on EEMD combined with FastICA.

Objective. The imaging photoplethysmography (IPPG), which is applied to heart rate measurement, is susceptible to interference caused by illumination variations during photography. To improve the accuracy, robustness, and real-time performance of IPPG, a new method combined with modified ensemble empirical mode decomposition (EEMD) and fast independent component analysis (FastICA) was proposed.Approach. On the modified EEMD, to reduce the error caused by the residual white noise of the algorithm, it was characterized by recurrently updating zero-mean white noise for ensemble averaging based on the standard deviation of the input signal. On the modified FastICA, its constructed nonlinear function was superseded by Huber's approximation function to improve the robustness and running speed.Main results. Comparison experiments were conducted between the MAHNOB-HCI database and own collected data. In the hybrid natural light and computer screen light scenario, the mean absolute error (MAE) of heart rate amounted to 0.93 beats per minute and the correlation coefficientrreached 0.85. In the experiments of MAHNOB-HCI database, the MAE amounted to 6.03 beats per minute and the correlation coefficientrreached 0.75. Furthermore, the modified method decreased the running time by approximately ten times compared to the original algorithms.Significance. Various experimental results demonstrated that the proposed method significantly improves the accuracy, timeliness, and interference resistance.

The overexpression of neurokinin B-neurokinin 3 receptor system exerts direct effects on the ovary under PCOS-like conditions to interfere with mitochondrial function.

PROBLEM: The increased hypothalamic neurokinin B (NKB) level may contribute to the hyperactive LH pulse secretion in Polycystic ovary syndrome (PCOS). However, the expression and role of the neurokinin B-neurokinin 3 receptor (NKB-NK3R) system in the local ovarian tissue of PCOS have not been clarified. We constructed in vivo and in vitro models to elucidate the mechanism of the NKB-NK3R pathway in reproductive endocrine disorders of PCOS. METHOD OF STUDY: The granulosa cell line-KGN cells were set in palmitic acid (PA) and dihydrotestosterone (DHT) to simulate the PCOS-like conditions. And we used the high-fat/high-glucose diet to build a PCOS-like mice model and neurokinin 3 receptor antagonist (NK3Ra) was administered to half of the mice. The expression of the NKB-NK3R system, mitochondrial functions, hormone levels, and inflammatory state was evaluated. RESULTS: The PCOS-like stimulations induced the NKB-NK3R system and MAPK-ERK pathway overexpression in KGN cells, in an approximate dose and time-dependent manner. The NKB-NK3R system overactivated the MAPK-ERK pathway to increase NNT overexpression, disturb NADH/NADPH pools, aggravate the oxidation state, and decrease ATP production. With overexpression of the NKB-NK3R system in the local ovarian tissue, ovulatory dysfunction, progesterone deficiency, and pro-inflammatory states were apparent in PCOS-like mice. Antagonizing the receptor, NK3R, reversed the adverse reproductive endocrine phenotypes via improving mitochondrial dysfunction. CONCLUSIONS: In addition to the central regulation, local ovarian overexpression of the NKB-NK3R system participated in the adverse reproductive endocrine phenotypes, supporting the therapeutic implications of NK3Ra for PCOS.

Neurokinin 3 receptor antagonist-induced adipocyte activation improves obesity and metabolism in PCOS-like mice.

AIMS: Neurokinin-B (NKB)-Neurokinin-3-receptor (NK3R) pathway is remarkably sensitive to energy equilibrium; however, its role in metabolic regulation remains unexplored in polycystic ovary syndrome (PCOS). Therefore, this work aimed to investigate the role of NK3R antagonists (NK3Ra) on metabolic dysfunction and obesity in in vitro and in vivo PCOS models. MAIN METHODS: First, an observational study using serum samples collected from 19 PCOS patients was performed. Second, prospective case-control experimental studies where NK3Ra (SB222200) was used to treat PCOS-like mice (BALB/c mice), ovariectomized+estrogen implanted obese mice (C57BL/6J mice) and 3T3-L1 murine preadipocytes were carried out to investigate its effect on metabolism in vivo and in vitro. The fat volumes, serum biochemical indexes, adipokines and inflammatory cytokines, metabolism-related gene expression and the concentrations of ATP, NAD+, NADPH…etc. were studied. KEY FINDINGS: We found a positive correlation between serum NKB and lipid metabolism indicators in PCOS women. Using the mouse models, we demonstrated that administration of NK3Ra regulates serum adipokines, inhibits weight gain with a marked decrease in fat volume, adipocyte size, and inflammatory cytokines, and promotes oxidative metabolism and energy consumption. NK3Ra reduces lipid accumulation in mature murine adipocytes by inhibiting the expression of peroxisome proliferator- activated receptor gamma (PPAR-γ) and fatty acid binding protein 4 (FABP4) genes. NK3Ras also enhances oxidative metabolism and energy consumption by maintaining intracellular redox homeostasis. SIGNIFICANCE: This study backs the use of NK3Ras as a potential therapeutic for PCOS since it ameliorates both reproductive and metabolic aberrations.

High Dielectric Transparent Film Tailored by Acceptor and Donor Codoping.

High dielectric constant materials are of particular current interests as indispensable components in transistors, capacitors, etc. In this context, there are emerging trends to exploit defect engineering in dielectric ceramics for enhancing the performance. However, demonstrations of similar high dielectric performance in integration-compatible crystalline films are rare. Herein, such a breakthrough via the functionalization of donor-acceptor dipoles by compositional tuning in GaCu codoped ZnO films is reported. The dielectric constant reaches ~200 at 1 kHz and the optical transmittance in visible light reaches ~80%. Importantly, by analyzing the impedance spectroscopy data, prominent relaxation mechanisms in correlation with the dipole properties, enabling consistent explanations of the dielectric constant as a function of frequency are discriminated. The atomistic nature of the dipoles is revealed by the systematic X-ray spectroscopy analysis. Spectacularly, similar trends for the dielectric properties are observed, while synthesizing samples by pulsed laser deposition and ion implantation, indicating the general character of the phenomena.

Mathematical Model for Skin Pain Sensation under Local Distributed Mechanical Compression for Electronic Skin Applications.

Skin pain resulting from mechanical compression is one of the most common pains in daily life and the indispensable information for electronic skin to perceive external signals. The external mechanical stimuli are transduced into impulses and transmitted via nerve fiber, and finally, the sensation is perceived via the procession of the nerve system. However, the mathematical mechanism for pain sensation due to mechanical stimuli remains unclear. In this paper, a mathematical model for skin pain sensation under compression is established, in which the Flament solution, the revised Hodgkin-Huxley model, and the mathematical model gate control theory are considered simultaneously. The proposed model includes three parts: a mechanical model of skin compression, a model of transduction, and a model of modulation and perception. It is demonstrated that the pain sensation degree increases with the compression amplitude and decreases with deeper nociceptor location in the skin. With the help of the proposed model, the quantitative relationship between compression pain sensation and external mechanical stimuli is revealed, which has a significant benefit in promoting the design and mechanism research of electronic skin with pain perception function.

Transient Heat Conduction in the Orthotropic Model with Rectangular Heat Source.

Epidermal electronic systems (EESs) are a representative achievement for utilizing the full advantages of ultra-thin, stretchable and conformal attachment of flexible electronics, and are extremely suitable for integration with human physiological systems, especially in medical hyperthermia. The stretchable heater with stable electrical characteristics and a uniform temperature field is an irreplaceable core component. The inorganic stretchable heater has the advantage of maintaining stable electrical characteristics under tensile deformation. However, the space between the patterned electrodes that provides tensile properties causes uneven distribution of the temperature field. Aiming at improving the temperature distribution uniformity of stretchable thermotherapy electrodes, an orthotropic heat transfer substrate for stretchable heaters is proposed in this paper. An analytical model for transient heat conduction of stretchable rectangular heaters based on orthotropic transfer characteristics is established, which is validated by finite element analysis (FEA). The homogenization effect of orthotropic heat transfer characteristics on temperature distribution and its evolutionary relationship with time are investigated based on this model. This study will provide beneficial help for the temperature distribution homogenization design of stretchable heaters and the exploration of its transient heat transfer mechanism.

Recent Advances in Flexible RF MEMS.

Microelectromechanical systems (MEMS) that are based on flexible substrates are widely used in flexible, reconfigurable radio frequency (RF) systems, such as RF MEMS switches, phase shifters, reconfigurable antennas, phased array antennas and resonators, etc. When attempting to accommodate flexible deformation with the movable structures of MEMS, flexible RF MEMS are far more difficult to structurally design and fabricate than rigid MEMS devices or other types of flexible electronics. In this review, we survey flexible RF MEMS with different functions, their flexible film materials and their fabrication process technologies. In addition, a fabrication process for reconfigurable three-dimensional (3D) RF devices based on mechanically guided assembly is introduced. The review is very helpful to understand the overall advances in flexible RF MEMS, and serves the purpose of providing a reference source for innovative researchers working in this field.

An Analytic Orthotropic Heat Conduction Model for the Stretchable Network Heaters.

Compared with other physiotherapy devices, epidermal electronic systems (EES) used in medical applications such as hyperthermia have obvious advantages of conformal attachment, lightness and high efficiency. The stretchable flexible electrode is an indispensable component. The structurally designed flexible inorganic stretchable electrode has the advantage of stable electrical properties under tensile deformation and has received enough attention. However, the space between the patterned electrodes introduced to ensure the tensile properties will inevitably lead to the uneven temperature distribution of the thermotherapy electrodes and degrade the effect of thermotherapy. It is of great practical value to study the temperature uniformity of the stretchable patterned electrode. In order to improve the uniformity of temperature distribution in the heat transfer system with stretchable electrodes, a temperature distribution manipulation strategy for orthotropic substrates is proposed in this paper. A theoretical model of the orthotropic heat transfer system based on the horseshoe-shaped mesh electrode is established. Combined with finite element analysis, the effect of the orthotropic substrate on the uniformity of temperature distribution in three types of heat source heat transfer systems is studied based on this model. The influence of the thermal conductivity ratio in different directions on the temperature distribution is studied parametrically, which will help to guide the design and fabrication of the stretchable electrode that can produce a uniform temperature distribution.

Design and Growth of Branched Organic Crystals: Recent Advances and Future Applications.

The rapid development of information technology has resulted in a growing demand for low-dimensional photonic materials. Organic semiconductor materials play an important role in various photonic devices due to their adjustable physicochemical properties, while individual organic crystals do not exhibit the desired performance due to the limitations of their simple structure. Branched organic crystals with inherent multichannel characteristics based on π-conjugated molecules are favorable components in optoelectronics. However, the preparation of branched organic crystals still faces great challenges before they can be applied in integrated optoelectronic devices. In this Review, the development and representative examples of branched organic crystals in terms of molecular design, synthesis, and advanced applications are discussed. We also provide a summary and outlook for the direction of future research on branched organic crystals as excellent candidates in photonic integrated circuits.

The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population.

Purpose: To exhibit the lipid profiles in PCOS women with different characteristics and to access correlations between alternation of key lipid parameters and characteristics of PCOS. Design: A retrospective study. Participants: A total of 700 PCOS women were included. Methods: Retrospective study on 700 women (age 24.6 ± 4.7 years), diagnosed with PCOS in the outpatient department of Obstetrics and Gynecology Hospital of Fudan University according to Rotterdam criteria. Anthropometric features, hormone levels, lipid levels, and metabolic parameters were measured and compared between PCOS patients with different characteristics. Results: There was a high prevalence of dyslipidemia among Chinese PCOS patients (41.3%), and the most common pattern was low HDL. Patients with clinical hyperandrogenism presented with significantly decreased HDL and Apo-A levels. The levels of TG, LDL, Apo-B, TG/HDL, and Apo-B/Apo-A were significantly increased in the insulin resistance subgroup. The levels of TC and TG were significantly increased in the dysglycemia and T2DM women. And in general, the levels of TG, and Apo-B had an increasing trend with BMI. Moreover, AI, TG/HDL, and Apo-B/Apo-A ratios were associated with some characteristics of PCOS, such as insulin resistance, and obesity. Conclusion: The PCOS women with different characteristics presented with different lipid profiles, and there is a complex correlation between lipid metabolism and PCOS characteristics, which may explain the increased risk of long-term cardiovascular disease. Regular screening of blood lipids is essential for PCOS women. Identification of optimal subgroups in PCOS patients that need lipid-lowering treatment and therapeutic effectiveness is worth exploring.

Altered Molecular Pathways and Biomarkers of Endometrial Receptivity in Infertile Women with Polycystic Ovary Syndrome.

Anovulation is the most prominent cause of infertility in polycystic ovary syndrome (PCOS) patients. Although ovulation can be corrected pharmacologically, the number of pregnancies remains low. Even if excellent embryos are transferred by IVF, it does not change the high miscarriage rate of PCOS patients. These facts collectively indicate that there is a disorder of endometrial development and receptivity to the embryo in PCOS patients, including the decrease of receptive ability, inhibition of embryo adhesion, undersupply of energy, poor blood perfusion, and pro-inflammatory status in the endometrium. However, it has never received the same attention as ovulatory dysfunction. Here we list some alternations of endometrial receptivity in women with PCOS, discuss the underlying intricate mechanisms, and try to find out the possible therapeutic targets, which may bring new perspectives to those who are able to provide high-quality embryos.

Effect of a high-calorie diet and constant light exposure on female reproduction, metabolism and immune inflammation: A comparative study of different mouse models.

PROBLEM: Excess caloric intake and irregular circadian rhythm could severely impair female reproductive, metabolic, and immune function. However, the similarities and differences between their individual and combined effects and mechanisms have not been fully elucidated. Due to limitations and confounding factors in clinical research, we used these two kinds of unhealthy factors to intervene the mice singly or in combination to explore their effects on individuals. METHOD OF STUDY: We used a high-calorie diet (HCD), constant light exposure (CLE), and a high-calorie diet combined with constant light exposure (HCD + CLE) to build three different mouse models. During the 9 weeks modeling period, the estrous cycles were monitored, and after modeling, the indicators of glycolipid metabolism, inflammation, and reproductive endocrine function were tested. RESULTS: We found that both HCD and CLE alone could induce ovulatory disorders, obesity, and chronic low-grade inflammation and inhibit melatonin secretion. The difference was that HCD significantly reduced the serum luteinizing hormone (LH) and testosterone (T) levels, inhibited the expression of FSH ß and LH ß in pituitary, increased cytochrome P450 enzymes and LH receptor expression in ovary, as well causing impaired glucose tolerance and hyperlipidemia, and significantly promoted the secretion of leptin and inhibited the secretion of adiponectin. However, CLE significantly increased blood LH and T, prompted the expression of kisspeptin in hypothalamus and LH ß in pituitary, and had no effect on glycolipid metabolic indexes or the secretion of leptin or adiponectin. The phenotype of HCD + CLE model was basically the same as that of HCD model, associated with more severe visceral obesity and chronic inflammation. CONCLUSIONS: In conclusion, we found that unhealthy lifestyle determines the phenotype of reproductive endocrine, immune, and metabolic disorders. These findings can provide theoretical support for the subsequent study of PCOS-like features.

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression.

HOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.