Modulating the Distribution of Formamidinium Iodide by Ultrahigh Humidity Treatment Strategy for High-Quality Sequential Vapor Deposited Perovskite.

The quality of two-step processed perovskites is significantly influenced by the distribution of organic amine salts. Especially, modulating the distribution of organic amine salts remains a grand challenge for sequential vapor-deposited perovskites due to the blocking effect of bottom compact PbI2. Herein, an ultrahigh humidity treatment strategy is developed to facilitate the diffusion of formamidinium iodide (FAI) from the top surface to the buried bottom interface on the sequential vapor-deposited bilayer structure. Both experimental and theoretical investigations elucidate the mechanism that moisture helps to i) create FAI diffusion channels by inducing a phase transition from α- to δ-phase in the perovskite, and ii) enhance the diffusivity of FAI by forming hydrogen bonds. This ultrahigh humidity treatment strategy enables the formation of a desired homogeneous and high-quality α-phase after annealing. As a result, a champion efficiency of 22.0% is achieved and 97.5% of its initial performance is maintained after aging for 1050 h under ambient air with a relative humidity of up to 80%. This FAI diffusion strategy provides new insights into the reproducible, scalable, and high-performance sequential vapor-deposited perovskite solar cells.

Lead Iodide Redistribution Enables In Situ Passivation for Blading Inverted Perovskite Solar Cells with 24.5% Efficiency.

Blade-coating stands out as an alternative for fabricating scalable perovskite solar cells. However, it demands special control of the precursor composition regarding nucleation and crystallization and currently exhibits lower performance than the spin-coating process. It is mainly the resulting film morphology and excess lead iodide (PbI2) distribution that influences the optoelectronic properties. Here, the effectiveness of introducing N-Methyl-2-pyrrolidone (NMP) to regulate the structure of the perovskite layer and the redistribution of PbI2 is found. The introduction of NMP leads to the accumulation of excess PbI2, mainly on the top surface, reducing residual PbI2 at the perovskite buried interface. This not only facilitates the passivation of perovskite grain boundaries but also eliminates the potential degradation of the PbI2 triggered by light illumination in the perovskite buried interface. The optimized NMP-modified inverted perovskite solar cell achieves a champion efficiency of 24.5%, among the highest reported blade-coated perovskite solar cells. Furthermore, 13.68 cm2 blading perovskite solar modules are fabricated and demonstrate an efficiency of up to 20.4%. These findings underscore that with proper modulation of precursor composition, blade-coating can be a feasible and superior alternative for manufacturing high-quality perovskite films, paving the way for their large-scale applications in photovoltaic technology.

saKLK1-374 is more difficult to induce KLK1 expression in normal prostate cell lines than that in prostate cancer cell lines: Rethinking the universality of RNA activation.

RNA activation, as a method of regulating gene expression at the transcriptional level, is far less widely used than RNA interference because of the insufficient understanding of the mechanism and the unstable success rate. It is necessary to analyze the failure cases of RNA activation to promote the application of RNA activation. When we validated the saRNAs designed to induce KLK1 expression, we found that saKLK1-374 can upregulate KLK1 expression in prostate tumor cell lines, but failed in normal prostate cell lines. To determine whether the RNA activation of normal cells is difficult only when the target gene is KLK1, we tested p21WAF1/CIP1 as the target gene in RNA activation experiments of normal and cancer prostate cells. Next, to determine whether the above phenomenon exists in other tissues, we used normal and cancerous bladder cells to perform RNA activation experiments with KLK1 and p21WAF1/CIP1 as targets. We have also extended the time from transfection to detection to evaluate whether a longer incubation time can make saRNA upregulate the target genes in normal cells. Fluorescently labeled dsRNA was transfected to evaluate the transfection efficiency, and the expression of Ago2 and IPO8 necessary for RNA activation was also detected. The p21WAF1/CIP1 could be significantly upregulated by saRNA in prostate cancer cells, but not in normal prostate cells. The expression of KLK1 in bladder-derived cell lines was extremely low and could not be induced by saRNA. The p21WAF1/CIP1 was upregulated by saRNA to a higher extent in bladder cancer cells but to a lower extent in normal bladder cells. Prolonging incubation time could not make saRNA induce the expression of target genes in normal cells. Compared with tumor cells used in this study, normal cells had lower transfection efficiency or lower expression of Ago2 and IPO8. Although it has been currently found that normal cell lines in the prostate and bladder might be more difficult to be successfully induced target gene expression by exogenous saRNA than tumor cells due to low transfection efficiency or Ago2 and IPO8 expression, it is not certain that this phenomenon occurs in other types of tissue. However, researchers still need to pay attention to the transfection efficiency and/or the expression levels of Ago2 and IPO8 when conducting RNA activation experiments in normal cells.

Low-Temperature Chemical Bath Deposition of Conformal and Compact NiOX for Scalable and Efficient Perovskite Solar Modules.

A scalable and low-cost deposition of high-quality charge transport layers and photoactive perovskite layers are the grand challenges for large-area and efficient perovskite solar modules and tandem cells. An inverted structure with an inorganic hole transport layer is expected for long-term stability. Among various hole transport materials, nickel oxide has been investigated for highly efficient and stable perovskite solar cells. However, the reported deposition methods are either difficult for large-scale conformal deposition or require a high vacuum process. Chemical bath deposition is supposed to realize a uniform, conformal, and scalable coating by a solution process. However, the conventional chemical bath deposition requires a high annealing temperature of over 400 °C. In this work, an amino-alcohol ligand-based controllable release and deposition of NiOX using chemical bath deposition with a low calcining temperature of 270 °C is developed. The uniform and conformal in-situ growth precursive films can be adjusted by tuning the ligand structure. The inverted structured perovskite solar cells and large-area solar modules reached a champion PCE of 22.03% and 19.03%, respectively. This study paves an efficient, low-temperature, and scalable chemical bath deposition route for large-area NiOX thin films for the scalable fabrication of highly efficient perovskite solar modules.

Reciprocally Photovoltaic Light-Emitting Diode Based on Dispersive Perovskite Nanocrystal.

Integrating highly efficient photovoltaic (PV) function into light-emitting diodes (LEDs) for multifunctional display is of great significance for compact low-power electronics, but it remains challenging. Herein, it is demonstrated that solution engineered perovskite nanocrystals (PNCs, ≈100 nm) enable efficient electroluminescence (EL) and PV performance within a single device through tailoring the dispersity and interface. It delivers the maximum brightness of 490 W sr-1  m-2 at 2.7 V and 23.2% EL external quantum efficiency, a record value for near-infrared perovskite LED, as well as 15.23% PV efficiency, among the highest value for nanocrystal perovskite solar cells. The PV-EL performance is well in line with the reciprocity relation. These all-solution-processed PV-LED devices open up viable routes to a variety of advanced applications, from touchless interactive screens to energy harvesting displays and data communication.

Molecule occupancy by a n-butylamine treatment to facilitate the conversion of PbI2 to perovskite in sequential deposition.

Herein, we propose a new approach of molecule occupancy via a vapor treatment to facilitate the conversion of PbI2 to perovskite in sequential deposition. We have shown that the morphology of PbI2 and the subsequent crystallization of perovskite can be effectively tuned, thus leading to the elimination of residual PbI2 and promotion of perovskite growth.

Trichalcogenasumanene ortho-Quinones: Synthesis, Properties, and Transformation into Various Heteropolycycles.

The regioselective transformation of heterobuckybowl trichalcogenasumanenes 1 a,b at peripheral butoxy groups afforded trichalcogenasumanene ortho-quinones 2 a,b. Compounds 2 a,b are distinct from 1 a,b in terms of their molecular geometry and electronic state; that is, they have a shallower bowl depth and show absorbance in the NIR region. The reaction of 2 a,b with diamines resulted in a variety of heteropolycycles, including molecular spoon 3 a-6 a, planar π-systems 3 b-6 b, and highly twisted [7-6-6]-fused systems 7 a,b. These new heteropolycycles had different optical/electrical properties: 4 a,b showed hole mobility of approximately 0.002 cm2 V-1 s-1 , 6 a displayed red emission in both solution and the solid state, and 7 a,b formed tight stacks of the curved π-surface.

Global chromosomal structural instability in a subpopulation of starving Escherichia coli cells.

Copy-number variations (CNVs) constitute very common differences between individual humans and possibly all genomes and may therefore be important fuel for evolution, yet how they form remains elusive. In starving Escherichia coli, gene amplification is induced by stress, controlled by the general stress response. Amplification has been detected only encompassing genes that confer a growth advantage when amplified. We studied the structure of stress-induced gene amplification in starving cells in the Lac assay in Escherichia coli by array comparative genomic hybridization (aCGH), with polymerase chain reaction (pcr) and DNA sequencing to establish the structures generated. About 10% of 300 amplified isolates carried other chromosomal structural change in addition to amplification. Most of these were inversions and duplications associated with the amplification event. This complexity supports a mechanism similar to that seen in human non-recurrent copy number variants. We interpret these complex events in terms of repeated template switching during DNA replication. Importantly, we found a significant occurrence (6 out of 300) of chromosomal structural changes that were apparently not involved in the amplification event. These secondary changes were absent from 240 samples derived from starved cells not carrying amplification, suggesting that amplification happens in a differentiated subpopulation of stressed cells licensed for global chromosomal structural change and genomic instability. These data imply that chromosomal structural changes occur in bursts or showers of instability that may have the potential to drive rapid evolution.

Evaluation of national fitness and national health development and coupling and coordination in 11 provinces and cities in Eastern China.

Under the influence of development strategies with regard to national fitness and health in China, the interactive development between national fitness and national health is becoming increasingly strong. To explore the coupling and coordination relationship between national fitness and national health, this paper conducts an empirical analysis of the coupling and coordination relationship between national fitness and national health in 11 provinces and cities in Eastern China using the entropy weight method, a coupling coordination model, spatial visualization of the coupling coordination degree and spatial autocorrelation analysis. The research confirms that the comprehensive development level of national fitness and national health in Eastern China shows a steady upward trend, with a lag in national fitness as a whole, and that the growth rate of national fitness development is faster than that of national health development. The coupling coordination degree of the two systems of national fitness and national health in Eastern China shows a slow upward trend, and the coupling coordination degree rises from barely coordinated to primary coordination. There are significant differences in the spatial pattern of coupling coordination: the spatial pattern from north to south generally shows 'low-high-high-low-high-low' characteristics, and the spatial spillover effect of coupling coordination in various regions has not yet appeared. The revised GM(1.1) prediction results indicate that the level and improvement rate of coupling coordination will accelerate significantly in the next 10 years, but the spatial differences will still exist. Finally, suggestions are proposed to optimize the coupling and coordinated development of national fitness and national health based on policy guarantees as well as strengthening and cross-regional cooperation.

YAP1 Recognizes Inflammatory and Mechanical Cues to Exacerbate Benign Prostatic Hyperplasia via Promoting Cell Survival and Fibrosis.

Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes-associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation-induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation-associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH-1 and WPMY-1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation-triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F-actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1.

OBJECTIVE: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis. METHODS: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH2O) or exposed to HHP (50 cmH2O or 100 cmH2O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism. RESULTS: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors. CONCLUSION: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1.

Exploring a ferroptosis and oxidative stress-based prognostic model for clear cell renal cell carcinoma.

Background: Ferroptosis is a newly defined cell death process triggered by increased iron load and tremendous lipid reactive oxygen species (ROS). Oxidative stress-related ferroptosis is of great important to the occurrence and progression of clear cell renal cell carcinoma (ccRCC), which is particularly susceptibility to ferroptosis agonist. Therefore, exploring the molecular features of ferroptosis and oxidative stress might guide the clinical treatment and prognosis prediction for ccRCC patients. Methods: The differentially expressed ferroptosis and oxidative stress-associated genes (FPTOSs) between normal renal and ccRCC tissues were identified based on The Cancer Genome Atlas (TCGA) database, and those with prognostic significances were applied to develop a prognostic model and a risk scoring system (FPTOS_score). The clinical parameter, miRNA regulation, tumor mutation burden (TMB), immune cell infiltration, immunotherapy response, and drug susceptibility between two FPTOS-based risk stratifications were determined. Results: We have identified 5 prognosis-associated FPTOSs (ACADSB, CDCA3, CHAC1, MYCN, and TFAP2A), and developed a reliable FPTOS_socre system to distinguish patients into low- and high-risk groups. The findings implied that patients from the high-risk group performed poor prognoses, even after stratified analysis of various clinical parameters. A total of 30 miRNA-FPTOS regulatory pairs were recognized to identify the possible molecular mechanisms. Meanwhile, patients from the high-risk group exhibited higher TMB levels than those from the low-risk groups, and the predominant mutated driver genes were VHL, PBRM1 and TTN in both groups. The main infiltrating immune cells of high- and low-risk groups were CD8+ T cells and resting mast cells, respectively, and patients from the high-risk groups showed preferable drug responsiveness to anti-PD-1 immunotherapy. Eventually, potential sensitive drugs (cisplatin, BI-D1870, and docetaxel) and their enrichment pathways were identified to guide the treatment of ccRCC patients with high-risk. Conclusion: Our study comprehensively analyzed the expression profiles of FPTOSs and constructed a scoring system with considerable prognostic value, which would supply novel insights into the personalized treatment strategies and prognostic evaluation of ccRCC patient.

Cryptotanshinone modulates proliferation, apoptosis, and fibrosis through inhibiting AR and EGFR/STAT3 axis to ameliorate benign prostatic hyperplasia progression.

Benign prostatic hyperplasia (BPH) is a chronic proliferative non-tumorous disease that mainly bothers males older than 50 and significantly disturbs the quality of life. Cryptotanshinone (CTS), a herbal extract, has been proven with therapeutic effects on various diseases. However, the effects and possible mechanisms of CTS in BPH have not yet been elucidated. This study aims to investigate the efficacy of CTS on the BPH-associated pathological processes and the possible mechanisms underlying it. Herein, CTS was intragastrically administrated to estradiol/testosterone (E2/T) (1:100)-induced BPH rats, and finasteride (Fi) was used as the positive control. Human benign prostatic hyperplasia epithelial cells (BPH-1) and normal human prostate stromal cells (WPMY-1) were used for the in vitro experiments. Results indicated that E2/T injection was able to induce BPH manifestation, featured with increased prostate index. Furthermore, it accelerated proliferation, epithelial-mesenchymal transition (EMT), stromal collagen deposition, and inhibited apoptosis of rat prostate. However, the administration of CTS partially reversed the changes mentioned above. The therapeutic effects of CTS on BPH were also confirmed by in vitro experiments. The efficacy of CTS on these processes might be attributed to the suppression of AR and EGFR/STAT3 axis activity. In conclusion, CTS might suppress BPH progression by modulating proliferation, apoptosis, EMT, and stromal collagen deposition via suppressing AR and EGFR/STAT3 axis.

A Pilot Study: Detrusor Overactivity Diagnosis Method Based on Deep Learning.

OBJECTIVE: To develop two intelligent diagnosis models of detrusor overactivity (DO) based on deep learning to assist doctors no longer heavily rely on visual observation of urodynamic study (UDS) curves. METHODS: UDS curves of 92 patients were collected during 2019. We constructed two DO event recognition models based on convolutional neural network (CNN) with 44 samples, and tested the model performance with the remaining 48 samples by comparing other four classical machine learning models. During the testing phase, we developed a threshold screening strategy to quickly filter out suspected DO event segments in each patient's UDS curve. If two or more DO event fragments are determined to be DO by the diagnostic model, the patient is diagnosed as having DO. RESULTS: We extracted 146 DO event samples and 1863 non-DO event samples from the UDS curves of 44 patients to train CNN models. Through 10-fold cross-validation, the training accuracy and validation accuracy of our models achieved the highest accuracy. In the model testing phase, we used a threshold screening strategy to quickly screen out the suspected DO event samples in the UDS curve of another 48 patients, and then input them into the trained models. Finally, the diagnostic accuracy of patients without DO and patients with DO was 78.12% and 100%, respectively. CONCLUSION: Under the available data, the accuracy of the DO diagnostic model based on CNN is satisfactory. With the increase of the amount of data, the deep learning model is likely to have better performance. CLINICAL TRIAL REGISTRATION: This experiment was certified by the Chinese Clinical Trial Registry (ChiCTR2200063467).

High glucose promotes benign prostatic hyperplasia by downregulating PDK4 expression.

As men age, a growing number develop benign prostatic hyperplasia (BPH). According to previous research, diabetes may be a risk factor. Pyruvate dehydrogenase kinase 4 (PDK4) is closely related to glucose metabolism and plays a role in the onset and progression of numerous illnesses. This study aimed to determine the direct effects of high glucose environment on prostate epithelial cells, in particular by altering PDK4 expression levels. In this investigation, normal prostatic epithelial cells (RWPE-1) and human benign prostatic hyperplasia epithelial cells (BPH-1) were treated with 50 mM glucose to show the alteration of high glucose in prostate cells. PDK4-target siRNA, PDK4-expression plasmid were used to investigate the effects of PDK4. Rosiglitazone (RG), a PPARγ agonist, with the potential to up-regulate PDK4 expression was also used for treating prostate cells. The expression of PDK4 in human prostate samples was also analyzed. The effects of high glucose therapy on BPH-1 and RWPE-1 cells were demonstrated to enhance proliferation, epithelial-mesenchymal transition (EMT), suppress apoptosis, and down-regulate PDK4 expression. Additionally, diabetes-related BPH patients had reduced PDK4 expression. Following the application of PDK4-target siRNA, a comparable outcome was seen. The PDK4-expression plasmid therapy, however, produced the opposite results. RG with the ability to elevate PDK4 expression might be used to treat BPH. Changes in the metabolism of lipids and glucose may be the cause of these consequences. These findings showed that high glucose treatment might facilitate BPH development, and may be related to the down-regulation of PDK4. PDK4 might be a potential therapeutic target of BPH.

The Expression and Function of Piezo Channels in Bladder.

The ability for bladder to perceive and analyze mechanical stimuli, such as stretch and filling, is crucial for its functions, such as urinary storage and voiding. The Piezo channel family, including Piezo1 and Piezo2, represents one of the most essential mechanosensitive ion channels in mammals and is involved in a wide array of physiological and pathological processes. It has been demonstrated in numerous investigations that Piezo channels play a key role in mechanical transduction in various types of cells in bladder by converting mechanical stimuli into biological signals. Notably, mounting evidence suggests that Piezo channels are functionally significant for bladder and are related to several bladder disorders. This review systematically summarizes the importance/role and features of Piezo channels in bladder, including their biophysical properties, location, and functions, with attention specifically paid to their association with the physiology and pathophysiology of bladder. This review aims to provide a novel perspective for the future clinical treatment of bladder dysfunction.

Buried Interface Dielectric Layer Engineering for Highly Efficient and Stable Inverted Perovskite Solar Cells and Modules.

Stability and scalability are essential and urgent requirements for the commercialization of perovskite solar cells (PSCs), which are retarded by the non-ideal interface leading to non-radiative recombination and degradation. Extensive efforts are devoted to reducing the defects at the perovskite surface. However, the effects of the buried interface on the degradation and non-radiative recombination need to be further investigated. Herein, an omnibearing strategy to modify buried and top surfaces of perovskite film to reduce interfacial defects, by incorporating aluminum oxide (Al2 O3 ) as a dielectric layer and growth scaffolds (buried surface) and phenethylammonium bromide as a passivation layer (buried and top surfaces), is demonstrated. Consequently, the open-circuit voltage is extensively boosted from 1.02 to 1.14 V with the incorporation of Al2 O3 filling the voids between grains, resulting in dense morphology of buried interface and reduced recombination centers. Finally, the impressive efficiencies of 23.1% (0.1 cm2 ) and 22.4% (1 cm2 ) are achieved with superior stability, which remain 96% (0.1 cm2 ) and 89% (1 cm2 ) of its initial performance after 1200 (0.1 cm2 ) and 2500 h (1 cm2 ) illumination, respectively. The dual modification provides a universal method to reduce interfacial defects, revealing a promising prospect in developing high-performance PSCs and modules.

Fast detection method for prostate cancer cells based on an integrated ResNet50 and YoloV5 framework.

PURPOSE: To propose a fast detection method for prostate cancer abnormal cells based on deep learning. The purpose of this method is to quickly and accurately locate and identify abnormal cells, so as to improve the efficiency of prostate precancerous screening and promote the application and popularization of prostate cancer cell assisted screening technology. METHOD: The method includes two stages: preliminary screening of abnormal cell images and accurate identification of abnormal cells. In the preliminary screening stage of abnormal cell images, ResNet50 model is used as the image classification network to judge whether the local area contains cell clusters. In the another stage, YoloV5 model is used as the target detection network to locate and recognize abnormal cells in the image containing cell clusters. RESULTS: This detection method aims at the pathological cell images obtained by the membrane method. And the double stage models proposed in this paper are compared with the single stage model method using only the target detection model. The results show that through the image classification network based on deep learning, we can first judge whether there are abnormal cells in the local area. If there are abnormal cells, we can further use the target detection method based on candidate box for analysis, which can reduce the reasoning time by 50% and improve the efficiency of abnormal cell detection under the condition of losing a small amount of accuracy and slightly increasing the complexity of the model. CONCLUSION: This study proposes a fast detection method for prostate cancer abnormal cells based on deep learning, which can greatly shorten the reasoning time and improve the detection speed. It is able to improve the efficiency of prostate precancerous screening.

Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis.

Purpose: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder. Although ferroptosis is closely associated with inflammation, oxidative stress, and neuropathic pain, its role in CP/CPPS has not yet been elucidated. Therefore, we sought to explore the role and mechanism of ferroptosis in the prostatitis development. Methods: The experimental autoimmune prostatitis (EAP) was established through intradermal immunization of prostate extract. Iron chelator deferoxamine (DFO) and free radical scavenger edaravone (EDA) were applied to evaluate the effects of ferroptosis inhibition on oxidative stress, ferroptosis, inflammation, fibrosis, and mast cell activation in the context of CP/CPPS. Results: Increased generation of lipid peroxidation products (ROS and MDA) and decreased activities of antioxidant enzymes (SOD and CAT) suggested an aberrant oxidative stress status in EAP model. Elevated iron concentration was observed in the EAP model. Meanwhile, we discovered significant biological performances associated with ferroptosis in CP/CPPS, including the downregulation of the system Xc-/GPX4 axis and the upregulation of the ACSL4/LPCAT3 axis. EAP rats performed serious leukocyte infiltration, advanced inflammatory grade, and abnormal expression of inflammatory mediators. Abundant collagen deposition, enhanced RhoA, ROCK1, and α-SMA protein levels indicated that EAP rats were prone to suffer from stromal fibrosis compared with control group. An elevated number of degranulated mast cells and corresponding marker TPSB2 represented that mast cell-sensitized pain was amplified in the EAP model. Furthermore, reduction of NRF2/HO-1 indicated a vulnerability of EAP towards ferroptosis response. However, application of DFO and EDA had partially reversed the adverse influences mentioned above. Conclusion: We first demonstrated that ferroptosis might be a crucial factor of chronic prostatitis progression. Inhibition of ferroptosis using DFO and EDA represented a promising approach for treating prostatitis by ameliorating inflammation, fibrosis, and mast cell activation.

Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way.

OBJECTIVE: The aim of this study was to investigate whether tissue kallikrein (KLK1) can protect the prostate from inflammatory damage and the mechanism involved in it. METHODS: A total of 50 male Wistar rats were used in this study. Initially, 20 rats were sacrificed to obtain the prostate antigen to induce experimental autoimmune prostatitis (EAP), and the remaining 30 rats were randomly divided into 5 experimental groups (normal control group (NC group), NC+KLK1 group (NCK group), EAP group, EAP+KLK1 group (EAPK group), and EAP+KLK1+HOE140 group (EAPKH group); n = 6). It should be explained that KLK1 mainly exerts its biological effects through bradykinin, and HOE140 is a potent and selective bradykinin receptor B2 (BDKRB2) antagonist. EAP was induced by intradermal injection of 15 mg/ml prostate antigen and complete Freund's adjuvant on days 0, 14, and 28. KLK1 was injected via tail vein at a dose of 1.5 × 10-3 PAN U/kg once a day, and HOE140 was administered by intraperitoneal injection at 20 µg/kg once every two days. Rats were sacrificed on day 42. The RNA and protein of the rat prostate were extracted to analyze the expression differences of KLK1, as well as the inflammation-, fibrosis-, and oxidative stress-related genes. The inflammatory cell infiltration and microvessel density of the prostate were also analyzed by pathological examination. In addition, pathological analysis was performed on prostate samples from patients undergoing benign prostate hyperplasia (BPH) surgery. RESULTS: The expression of KLK1 in the prostate decreased in the EAP group as well as BPH patients with obvious inflammation. KLK1 administration significantly inhibited inflammatory cell infiltration and reduced the production of inflammatory cytokines in the EAPK group. Prostate samples from the EAP group showed increased infiltration of T cells and macrophages, as well as gland atrophy, hypoxia, fibrosis, and angiogenesis. KLK1 administration upregulated endothelial nitric oxide synthase (eNOS) expression and suppressed oxidative stress, as well as transforming growth factor ß1 (TGF-ß) signaling pathways and the proangiogenic vascular endothelial growth factor (VEGF) in the EAPK group. However, in the EAPKH group in which HOE140 blocked BDKRB2, the beneficial effects of KLK1 were all cancelled. In addition, KLK1 intervention in normal rats had no obvious side effects. CONCLUSION: The KLK1 expression is inhibited in the inflamed prostates of humans and rats. Exogenous KLK1 restored endothelial function via a BDKRB2-dependent way and then played a role in improving microcirculation and exerted anti-inflammatory, antifibrotic, and antioxidative stress effects in the rat chronic-inflamed prostate.