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Abstract To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P

Dendritic cells, which are crucial for inducing T-cell responses, are pivotal in current immunotherapy strategies aiming to replenish depleted T cells within the tumor microenvironment to combat tumors. Consequently, dendritic cell vaccine-based cancer therapies have garnered significant attention. Through bibliometric analysis, we examined research trends in this field. We searched the Web of Science core database and identified 16,476 articles on dendritic cell-based vaccines published from January 1, 2009, to December 30, 2023. The United States leads in this research domain, with Emory University being a prominent collaborator. The Journal of Immunology is the primary publication outlet, and Banchereau, J emerges as the most influential author. Recent hot keywords include nanoparticle, delivery, cancer vaccine, and clinical trial, indicating that cancer immunotherapy research, especially dendritic cell-based vaccines, is poised to become a future trend and hotspot.

Abstract 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.

Two-dimensional semiconductors simultaneously having suitable electronic properties and high carrier motilities are highly required in next-generation photoelectronic devices. Herein, we propose a new single-layer semiconductor, CdIn2S4, and investigate its photoelectronic properties utilizing first-principles calculations. Interestingly, we find that single-layer CdIn2S4 holds a quasi-direct moderate bandgap of 1.73 eV. Its valence band maximum and conduction band minimum are located at different atomic regions, which hinders the recombination of generated electrons and holes. Hence, single-layer CdIn2S4 has a suitable electronic structure for optoelectronics. The suitable electronic property also exists under the biaxial strains of −4%, −2%, 2 %, and 4 %, while the electron mobility ranges from ∼3000 to ∼11,000 cm2·V−1·s−1, revealing its potential application in high-speed electronics. In addition, its strong visible absorption and much-reduced exciton binding energy render abundant photogenerated electrons and holes. Summarily, the suitable electronic property, ultrahigh carrier mobility, and abundant visible absorption demonstrate that single-layer CdIn2S4 is a hopeful candidate for high-speed optoelectronics.

Due to the poor stability and adverse effects of chemotherapy drugs, such as gemcitabine, the current effectiveness of traditional chemotherapy is minimal. Some patients also show a low response rate to immunotherapy. Therefore, a novel material PD‐L1‐GEMs is designed and synthesized with targeted specificity. PD‐L1‐GEMs specifically bind to bladder cancer cells. Free gemcitabine cleaved by a phosphatase enters bladder cancer cells through the macropinocytosis pathway and induces cytotoxicity. PD‐L1‐GEMs show good stability, binding specificity, and significant inhibitory effects in vitro. Two bladder tumor models (subcutaneous model and in situ model) show inhibition of growth and progression in PD‐L1‐GEMs treatment, as well as good biosafety in vivo. The PD‐L1 aptamer blocks the binding of PD‐L1 on the tumor cell surface to PD‐1 on T lymphocytes, restoring their immune function, inducing cytokine production and aggregation, and exerting an immune killing role on bladder cancer cells. PD‐L1‐GEMs represent a successful chemotherapy–immunotherapy strategy for bladder cancer.

To enhance the precision of predicting enterprise credit risk related to carbon emission reduction, this study focuses on publicly traded companies. It introduces a risk early warning model grounded in MLP deep learning. Primarily, this research employs the FA-TOPSIS fusion model to comprehensively assess the credit risk associated with carbon emission reduction in enterprises. Subsequently, it employs K-means clustering to compute enterprise similarities, which forms the basis for supervised learning in the MLP model to assign credit risk grade labels. Furthermore, the study tackles the challenge of imbalanced enterprise grade distribution using the ADASYN over-sampling algorithm. Ultimately, the effectiveness of the model proposed herein is confirmed through a series of multi-model comparison experiments. The results show that: First, carbon emission reduction indicators exhibit differing degrees of influence on enterprises at various credit risk levels. Notably, the most influential indicator is carbon emission intensity, while the development capacity indicator exerts the least influence. Second, the adoption of the XGBoost algorithm for screening carbon emission reduction indicators significantly enhances the prediction accuracy of the early warning model by 4.27%. Third, compared to other models, the MLP model achieves an impressive prediction accuracy of 99.48%, representing an average improvement of 15.24%. These results underscore the model’s feasibility and its potential to provide technical support for financial institutions and government entities in conducting credit ratings for enterprise carbon emission reduction.

Two-dimensional (2D) semiconductors with intrinsic dipole show glorious prospects in the fields of nanoelectronics. Herein, the possible applications of single-layer GaInO3 in the realms of optoelectronics and piezoelectricity are investigated via the first-principles study. We find that single-layer GaInO3 exhibits a large vertical dipole moment and a direct bandgap (1.53 eV). Its transport mobility for electrons and holes both surpasses 2000 cm2·V−1·s−1. The effective separation of charge carriers for single-layer GaInO3 is confirmed by the strong inside electric field and the spatially isolated conduction band minimum (CBM) and valence band maximum (VBM). The allowed optical transition makes single-layer GaInO3 a hopeful candidate for optical absorbers and detectors. Finally, we also find that single-layer GaInO3 holds a prominently stronger out-of-plane piezoelectric effect than that of previous 2D materials and will play a big role in modern top-bottom gate technologies. In summary, this work proves that single-layer GaInO3 is a promising candidate for atomic-thick optoelectronic and piezoelectric devices.

This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression (P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.

Abstract Background Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC. Methods Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays. Results PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models. Conclusion These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Objective: To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy. Materials and methods: A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and who underwent penectomy were included in the study. The optimal cut-off value of the PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan–Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between the PNI, AGR, and OS in patients with PC. Results: A total of 16 of the 123 patients died during the follow-up period, and the median follow-up time was 58.0 months. The best cut-off values of the PNI and AGR were set to 49.03 (95% confidence interval 0.705–0.888, Youden index = 0.517, sensitivity = 57.9%, specificity = 93.7%, p < 0.001) and 1.28 (95% confidence interval 0.610–0.860, Youden index = 0.404, sensitivity = 84.1%, specificity = 56.2%, p = 0.003). The Kaplan–Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (p < 0.001). The univariable analysis showed that the aCCI, the clinical N stage, the pathological stage, and the PNI, AGR, SII, and PLR are all predictors of OS in patients with PC (p < 0.05). The multivariable analysis showed that the PNI (risk rate [HR] = 0.091; 95% CI: 0.010–0.853; p = 0.036) and the AGR (risk rate [HR] = 0.171; 95% CI: 0.043–0.680; p = 0.012) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy. Conclusions: Both the PNI score and the serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.

Two-dimensional optoelectronic materials with desirable bandgaps and high carrier separation efficiency are in urgent need. Herein, single-layer ZnGaInS4 is designed and thoroughly studied by first-principles calculations. Our calculations reveal the excellent stability of single-layer ZnGaInS4, and the small cleavage energy demonstrates the feasibility to exfoliate single-layer ZnGaInS4 from bulk counterparts. At the HSE06 level, single-layer ZnGaInS4 has a moderate bandgap of 2.05 eV, and its valence band maximum and conduction band minimum are spatially separated, thus impeding the electron-hole pair formation and enhancing the photoelectronic performance. In the visible region, single-layer ZnGaInS4 exhibits an optical absorption coefficient of ∼ 105 cm−1. Notably, single-layer ZnGaInS4 possesses high electron carrier mobility and low hole carrier mobility, further affirming the effective carrier separation. Another attractive characteristic is that single-layer ZnGaInS4 has anisotropic hole mobility. The desirable bandgap and high separation efficiency of generated carriers, together with abundant optical absorption, promise single-layer ZnGaInS4 is a hopeful candidate in atomic-thick optoelectronic devices.

ObjectiveTo explore whether type III prostatitis is related to bacterial infection by detecting the composition and function of microorganisms in expressed prostatic secretion (EPS) of patients with chronic prostatitis (CP) and healthy people.MethodsAccording to the inclusion and exclusion criteria, 57 subjects were included in our study, divided into the healthy group, type II prostatitis group, and type III prostatitis group. 16s rRNA sequencing technique was used to detect and analyze the microbial composition of EPS in each group. Additionally, the metagenomics sequencing technique was used to further explore the function of different bacteria in the type III prostatitis group. Data analysis was performed by bioinformatics software, and the results were statistically significant when P

Abstract Uncontrolled epithelial cell proliferation in the prostate transition zone and the hyper-accumulation of mesenchymal-like cells derived from the epithelial-mesenchymal transition (EMT) of prostatic epithelium are two key processes in benign prostatic hyperplasia (BPH). m6A RNA modification affects multiple cellular processes, including cell proliferation, apoptosis, and differentiation. In this study, the aberrant up-regulation of methylase METTL3 in BPH samples suggests its potential role in BPH development. Elevated m6A modification in the prostate of the BPH rat was partially reduced by METTL3 knockdown. METTL3 knockdown also partially reduced the prostatic epithelial thickness and prostate weight, significantly improved the histological features of the prostate, inhibited epithelial proliferation and EMT, and promoted apoptosis. In vitro, METTL3 knockdown decreased TGF-β-stimulated BPH-1 cell proliferation, m6A modification, and EMT, whereas promoted cell apoptosis. METTL3 increased the m6A modification of PTEN and inhibited its expression through the reading protein YTHDF2. PTEN knockdown aggravated the molecular, cellular, and pathological alterations in the prostate of BPH rats and amplified TGF-β-induced changes in BPH-1 cells. More importantly, PTEN knockdown partially abolished the improving effects of METTL3 knockdown both in vivo and in vitro. In conclusion, the level of m6A modification is elevated in BPH; the METTL3/YTHDF2/PTEN axis disturbs the balance between epithelial proliferation and apoptosis, promotes EMT, and accelerates BPH development in an m6A modification-related manner.

Summary: Oxygen redox electrocatalysis is the crucial electrode reaction among new-era energy sources. The prerequisite to rationally design an ideal electrocatalyst is accurately identifying the structure-activity relationship based on the so-called descriptors which link the catalytic performance with structural properties. However, the quick discovery of those descriptors remains challenging. In recent, the high-throughput computing and machine learning methods were identified to present great prospects for accelerating the screening of descriptors. That new research paradigm improves cognition in the way of oxygen evolution reaction/oxygen reduction reaction activity descriptor and reinforces the understanding of intrinsic physical and chemical features in the electrocatalytic process from a multiscale perspective. This review summarizes those new research paradigms for screening multiscale descriptors, especially from atomic scale to cluster mesoscale and bulk macroscale. The development of descriptors from traditional intermediate to eigen feature parameters has been addressed which provides guidance for the intelligent design of new energy materials.

Cancer stem cells (CSCs) are believed to be the main cause of chemotherapy resistance and tumor relapse. Various therapeutic strategies to eliminate CSCs have been developed recently. Aptamers, also called “chemical antibodies”, can specifically bind with their molecular targets through special tertiary structures. The advantages of aptamers, such as lower immunogenicity and smaller size, make them superior to conventional antibodies. Therefore, aptamers have been used widely as targeting ligands for CSC-targeted therapeutic strategies in different tumor types. To date, various therapeutic cargoes have been conjugated to aptamers to kill CSCs, such as chemotherapy drugs, small interfering RNAs, and microRNAs. Aptamer-based targeted therapies for CSCs have made great progress in recent years, especially the development of multifunctional aptamer-based therapeutic strategies. Besides, cell-systematic evolution of ligands by exponential enrichment has been applied to screen new aptamers that might have a higher binding ability for CSCs. In this review, we focus on recent advances and introduce some new modalities of aptamer-drug conjugates against CSCs. Some considerations of the advantages and limitations of different aptamer-based targeted therapies for CSCs are also discussed.

BackgroundThis study used bibliometrics to define and analyze the characteristics of the first 100 most cited papers on the topic of neuroendocrine prostate cancer (NEPC).MethodsWe explored the Web of Science Core Collection database, and screened the top 100 most frequently cited articles and reviews with the title NEPC or small cell prostate cancer (SCPC). We conducted bibliometrics research on the screening results to identify the most influential journals and authors in the field of NEPC.ResultsThe first 100 most cited papers have been cited a total of 14,795 times, from 73 to 833 times (mean ± standard deviation, 147.95 ± 101.68). All top 100 most cited papers were published from 1984 to 2019, and the total number of citations for papers published in 2016 was significantly higher than that for papers published in other years. The journal with the largest number of published papers is “Prostate” (n=8). “Neuroendocrine differentiation” has become the most frequently used author keyword. “Oncology” is the most popular topic in the field of NEPC.ConclusionWe analyzed the first 100 most cited papers in the NEPC field by collecting detailed information, which provide guiding opinions for finding the most influential journals and authors in NEPC-related fields. We hope to help researchers and readers in this field improve their understanding of NEPC research trends and provide ideas for future research from a unique perspective.

Abstract Background Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/si-circPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression. Conclusion The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64–2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74–2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80–2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

With rapid urbanization and population growth, achieving equitable distribution of urban facilities in the city center has become a critical research focus due to limited land space and high population density. In this study, we propose a technical method to measure the spatial matching between urban service facilities and population at the grid resolution scale, using Baidu heat map and POI data. The method includes spatial heterogeneity analysis and spatial matching analysis between population density and service facilities. We apply the method to the main urban area of Lanzhou, a valley-type city in the upper reaches of the Yellow River, and measure the spatial matching between service facilities and population aggregation. Our results reveal the distribution characteristics of various service facilities and population aggregation in different time slots, and demonstrate that transportation facilities have the highest spatial matching with population aggregation, followed by real estate and education services, with rental business services exhibiting the lowest. The proposed method offers a new perspective for urban planners and decision-makers to understand the matching state between residents’ activity patterns and service facilities. Our findings can provide theoretical support for urban planning and optimize the layout of service facilities and regional function allocation.

Abstract Antisense long non-coding RNAs (antisense lncRNAs), transcribed from the opposite strand of genes with either protein coding or non-coding function, were reported recently to play a crucial role in the process of tumor onset and development. Functionally, antisense lncRNAs either promote or suppress cancer cell proliferation, migration, invasion, and chemoradiosensitivity. Mechanistically, they exert their regulatory functions through epigenetic, transcriptional, post-transcriptional, and translational modulations. Simultaneously, because of nucleotide sequence complementarity, antisense lncRNAs have a special role on its corresponding sense gene. We highlight the functions and molecular mechanisms of antisense lncRNAs in cancer tumorigenesis and progression. We also discuss the potential of antisense lncRNAs to become cancer diagnostic biomarkers and targets for tumor treatment.

Abstract Background For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. Results The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. Conclusions The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. Graphic abstract

The tumor microenvironment (TME) is a microecology consisting of tumor and mesenchymal cells and extracellular matrices. The TME plays important regulatory roles in tumor proliferation, invasion, metastasis, and differentiation. Neuroendocrine differentiation (NED) is a mechanism by which castration resistance develops in advanced prostate cancer (PCa). NED is induced after androgen deprivation therapy and neuroendocrine prostate cancer (NEPC) is established finally. NEPC has poor prognosis and short overall survival and is a major cause of death in patients with PCa. Both the cellular and non-cellular components of the TME regulate and induce NEPC formation through various pathways. Insights into the roles of the TME in NEPC evolution, growth, and progression have increased over the past few years. These novel insights will help refine the NEPC formation model and lay the foundation for the discovery of new NEPC therapies targeting the TME.

Abstract The rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC tumors, patient-derived xenografts, transgenic mice, and cell models. Results from cell lines uncovered that ADT represses EHF expression, which is required for the ADT-induced NED. Mechanism dissection revealed that ADT decreases the EHF transcription via relieving the AR binding to different androgen-responsive elements, which then promotes the expression and enzymatic activity of enhancer of zeste homolog 2 (EZH2), consequently catalyzing tri-methylation lysine 27 of histone H3 for transcriptional repression of its downstream genes to promote the NED. Furthermore, preclinical studies from cell and mice models proved that recovery of EHF expression or using EZH2 inhibitor can attenuate aggressive properties of CRPC cells, hinder the progression of t-NEPC, and promote the response of CPRC cells to enzalutamide. Together, we elucidate that the ADT/AR/EHF/EZH2 signaling is required for the ADT-enhanced NED and plays a critical role in the progression of t-NEPC.

Abstract Similar to sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE), T2-weighted fast field echo (FFE) also has a black blood effect and a high imaging efficiency. The purpose of this study was to optimize 3D_T2_FFE and compare it with 3D_T2_SPACE for carotid imaging. The scanning parameter of 3D_T2_FFE was optimized for the imaging of the carotid wall. Twenty healthy volunteers and 10 patients with carotid plaque underwent cervical 3D_T2_FFE and 3D_T2_SPACE examinations. The signal-to-noise ratios of the carotid wall (SNRwall) and lumen (SNRlumen), and the contrast-to-noise ratios between the wall and lumen (CNRwall_lumen) were compared. The incidence of the residual flow signal at the carotid bifurcation and the grades of flow voids in the cerebellopontine angle region in the two sequences were also compared. The reproducibility of the two sequences was tested. No significant difference was observed between the two sequences in terms of the SNRwall of healthy individuals and patients (P = 0.132 and 0.102, respectively). The SNRlumen in the 3D_T2_FFE images was lower than that in the 3D_T2_SPACE images. No significant difference was observed between the two sequences in terms of the CNRwall-lumen. The incidence of the residual flow signal at the carotid bifurcation in 3D_T2_FFE was significantly lower than that in 3D_T2_SPACE. The grades of flow suppression in the cerebellopontine angle region in 3D_T2_SPACE was lower than that in 3D_T2_FFE. Both sequences showed excellent inter-and intra-observer reproducibility. Compared to 3D_T2_SPACE, 3D_T2_FFE showed stronger flow suppression while maintaining good imaging quality, which can be used as an alternative tool for carotid imaging.

Summary: Sulfonated polyphenylenes (SPPs) are one of the most promising polymers as proton exchange membranes for fuel cells (PEMFCs) because of their high proton conductivity, gas impermeability, and chemical and thermal stability. Mechanical stability needs further improvement for practical applications. Here we describe a protocol for the preparation and characterization of tetrafluorophenylene-containing SPP (SPP-TP-f) membranes reinforced with double porous ePTFE (expanded polytetrafluoroethylene) thin layers. The protocol also includes performance and durability evaluation of fuel cells using the reinforced membranes.For complete details on the use and execution of this protocol, please refer to Long and Miyatake (2021a).

Purpose: Benign prostatic hyperplasia-associated massive hemorrhage is a urological emergency. We evaluated the outcome from immediate transurethral plasma kinetic enucleation of the prostate gland (i-TUPKEP) for BHM treatment.Methods: We retrospectively analyzed the records of 49 patients with acute BMH who underwent i-TUPKEP between January 2014 and November 2018 at our institution. The hemostatic effect, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were evaluated preoperatively as well as 3, 6, and 12 months postoperatively. Postoperative follow-up also included measurement of the peak flow rate (Qmax) and post-void residual urine volume (PVR). Clinical characteristics, weight of resected tissue, duration of bladder irrigation, duration of hospital stay, complications, as well as the time required for enucleation and resection, were recorded.Results: BMH causes were attributed to transurethral surgery (17/49, 34.7%), violent catheterization (13/49, 26.5%), cystoscopy (10/49, 20.4%), and urethral dilatation (9/49, 18.4%). Bleeding was from different sites of prostate-gland tissues during i-TURKEP. i-TUPKEP-controlled BMH effectively induced immediate, notable, and lasting improvements in the IPSS and QoL score. Qmax was close to normal, and the PVR was within the physiological range, postoperatively. Long-term complications were not observed.Conclusion: Our preliminary data suggest that i-TUPKEP is a feasible method for controlling BHM and relieving BPH symptoms.

Eco-efficiency is a key indicator to measure the level of regional sustainable development. The county is the basic spatial unit of socio-economic activities and sustainable policy implementation in China. Hence, this paper conducts eco-efficiency analysis at the county scale in order to provide reference for the central and local governments to formulate differentiated eco-efficiency enhancement policies, further promote Chinese ecological sustainable development, and advance the construction of ecological civilization with high quality. Based on the Super-Slacks-Based Measure (SBM) model and the Malmquist index, the paper constructed an eco-efficiency measurement method and analyzed the variation characteristics, influencing factors, spatial pattern of eco-efficiency in Chinese counties from 2000 to 2020. The results showed that: (1) The eco-efficiency of the county unit was generally low in China and was roughly distributed in a pyramid. The county-level eco-efficiency had a spatial distribution pattern of being high in the west and low in the east, and high in the south and low in the north, with significant non-equilibrium. There was a positive correlation between eco-efficiency of neighboring counties in China. (2) The per-capita GDP has a significant positive correlation with eco-efficiency, while energy consumption, arable land area and eco-efficiency have a negative correlation. The redundancy rate of input indicators was high in Chinese counties. (3) During the study period, the eco-efficiency of most counties displayed a fluctuating growth trend. The growth was mainly driven by technological progress.

The linear mRNAs transcribed under alternative RNA splicing and overexpression/amplification of the androgen receptor (AR) gene are poor prognostic biomarkers of castrate-resistant prostate cancer (PCa). Whether the AR gene also transcribes non-coding circular RNAs that are associated with PCa development and tumor progression remains unclear. Here, we identified and characterized an AR circular RNA, called circAR3, that is widely expressed in PCa cell models and prostate tumors. circAR3 can be secreted into culture media of PCa cell lines and is detectable in the serum from mice bearing PCa xenografts. In PCa patient tissues, circAR3 is highly expressed in benign prostate and hormone naive PCa but downregulated when tumors were treated with neoadjuvant hormone therapy and further reduced when tumors progressed to the castrate-resistant stage. However, circAR3 levels in plasma are extremely low in patients with benign prostate, are upregulated in PCa patients with high Gleason scores and lymph node metastasis, and become undetectable in men after radical prostatectomy. circAR3 does not affect AR signaling, PCa cell proliferation, and invasion rates. Our results demonstrated that the origin of the detectable plasma circAR3 is from the prostate/PCa. Plasma circAR3 may be developed to be a PCa biomarker to monitor PCa development and tumor progression. Keywords: prostate cancer, androgen receptor, circular RNA, circAR3, alternative RNA splicing, cell-free circular RNA, AR splice variant

Background Primary congenital hypothyroidism (CH) is a common endocrine and metabolic disease. Various genetic factors, including the thyroid hormone receptor (TSHR), play an important role in CH. Aim To explore the occurrence of pathogenic TSHR variants in CH. Methods We searched published articles in PubMed, Web of Science, and Cochrane Library databases, from the establishment of the database to September 26, 2021. Studies with sequencing partial or full exons of TSHR in CH patients were included. Gene polymorphism was excluded. Results A total of 66 articles (44 case-control studies and 22 case reports) were selected from the database. Though case-control studies, we found the incidence of pathogenic TSHR variants were not rare (range from 0% to 30.6%) and varied greatly in different countries and race. The pathogenic genotypes varied in different regions. All the variants were “loss-of-function” mutations, in which the p.(Arg450His) variant was the most common variant. In addition, we analyzed the case reports and found that CH patients with a family genetic background expressed homozygous genotypes. Homozygotes had more obvious symptoms of hypothyroidism and higher risk of comorbidities than heterozygotes. Conclusion Pathogenic TSHR variants are not uncommon cause of the CH, especially in the Arabs. The role of TSHR gene detection in the treatment of children with CH needs to be further studied.

Summary: Sulfonated polyphenylene (SPP)-based ionomers have been developed for electrochemical applications in recent years due to their inherent thermal and chemical stability. However, the difficult synthesis, limited solubility, and rigid backbone obstructs their progress. Herein, a new monomer, 3,3″-dichloro-2′,3′,5′,6′-tetrafluoro-1,1':4′,1″-terphenyl (TP-f) with high polymerization reactivity was designed and polymerized with sulfonated phenylene monomer to prepare SPP-based ionomers (SPP-TP-f) with high ion exchange capacity up to 4.5 mequiv g−1. The resulting flexible membranes were more proton conductive than Nafion (state-of-the-art proton exchange membrane) even at 120°C and 20% RH. Unlike typical SPP ionomers, SPP-TP-f 5.1 was soluble in ethanol and thus, could be reinforced with double expanded polytetrafluorethylene thin layers to obtain SPP-TP-f 5.1/DPTFE membrane. SPP-TP-f 5.1/DPTFE showed superior fuel cell performance to that of Nafion, in particular, at low humidity (30% RH, > 100°C) and reasonable durability under the severe accelerated conditions combining OCV hold and humidity cycling tests.

Abstract The state-dependent impulsive dynamical system with boundary constraints is a kind of special but common system in nature. But because of the complexity of the geometry or topological structures of the impulsive surface, it is hard to determine when an event or an impulsive surface is reached. Therefore, a general state-dependent impulsive nonlinear dynamical system is rarely studied. This paper presents a class of state-dependent impulsive dynamical systems with boundary constraints. We obtain the existence and continuation of their viable solutions and provide sufficient conditions for the existence and uniqueness of the viable solutions to the system. Finally, two examples are given to illustrate the effectiveness of the results.

The pretreatment serum albumin/globulin ratio (AGR) has been used as a prognostic biomarker for various cancer types. However, the prognostic value of the AGR for prostate cancer, especially for metastatic prostate cancer (mPCa) after maximal androgen blockade (MAB), remains unclear. The aim of this study was to evaluate the prognostic value of the pretreatment serum AGR for mPCa treated with MAB. This retrospective study included 214 mPCa patients receiving MAB from October 2007 to March 2017. The correlation of the AGR with survival was estimated using Kaplan–Meier analysis and Cox proportional hazards models. The cutoff value of the AGR was 1.45 according to the receiver operating characteristic curve. Kaplan–Meier analysis demonstrated that patients with a low AGR (

To achieve low-carbon and sustainable development it is imperative to explore water treatment technologies in a carbon-neutral model. Because of its advantages of high efficiency, low consumption, and no secondary pollution, electrocatalytic oxidation technology has attracted increasing attention in tackling the challenges of organic wastewater treatment. The performance of an electrocatalytic oxidation system depends mainly on the properties of electrodes materials. Compared with the instability of graphite electrodes, the high expenditure of noble metal electrodes and boron-doped diamond electrodes, and the hidden dangers of titanium-based metal oxide electrodes, a titanium sub-oxide material has been characterized as an ideal choice of anode material due to its unique crystal and electronic structure, including high conductivity, decent catalytic activity, intense physical and chemical stability, corrosion resistance, low cost, and long service life, etc. This paper systematically reviews the electrode preparation technology of Magnéli phase titanium sub-oxide and its research progress in the electrochemical advanced oxidation treatment of organic wastewater in recent years, with technical difficulties highlighted. Future research directions are further proposed in process optimization, material modification, and application expansion. It is worth noting that Magnéli phase titanium sub-oxides have played very important roles in organic degradation. There is no doubt that titanium sub-oxides will become indispensable materials in the future.

Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that becomes more prevalent when hormonal therapy, chemotherapy, or radiation therapy is applied to patients with metastatic prostate adenocarcinoma (AdPC). How AdPC cells survive these anti-cancer therapies and progress into t-NEPC remains unclear. By comparing the whole transcriptomes between AdPC and t-NEPC, we identified Bif-1, an apoptosis-associated gene, which undergoes alternative RNA splicing in t-NEPC. We found that while Bif-1a is the predominant variant of the Bif-1 gene in AdPC, two neural-specific variants, Bif-1b and Bif-1c, are highly expressed in t-NEPC patients, patient derived xenografts, and cell models. The neural-specific RNA splicing factor, SRRM4, promotes Bif-1b and Bif-1c splicing, and the expression of SRRM4 in tumors is strongly associated with Bif-1b/-1c levels. Furthermore, we showed that Bif-1a is pro-apoptotic, while Bif-1b and Bif-1c are anti-apoptotic in PCa cells under camptothecin and UV light irritation treatments. Taken together, our data indicate that SRRM4 regulates alternative RNA splicing of the Bif-1 gene that enables PCa cells resistant to apoptotic stimuli under anti-cancer therapies, and may contribute to AdPC progression into t-NEPC. Keywords: Bif-1, SRRM4, Alternative RNA splicing, Neuroendocrine prostate cancer, Apoptosis

Abstract In present work, in order to avoid the spread of disease, the impulse control strategy is implemented to keep the density of infections at a low level. The SIR epidemic model with resource limitation including a nonlinear impulsive function and a state-dependent feedback control scheme is proposed and analyzed. Based on the qualitative properties of the corresponding continuous system, the existence and stability of positive order-k ( k ∈ Z + $k\in\mathbf{Z}^{+}$ ) periodic solution are investigated. By using the Poincaré map and the geometric method, some sufficient conditions for the existence and stability of positive order-1 or order-2 periodic solution are obtained. Moreover, the sufficient conditions which guarantee the nonexistence of order-k ( k ≥ 3 $k\geq3$ ) periodic solution are given. Some numerical simulations are carried out to illustrate the feasibility of our main results.