An RNA aptamer photoelectrochemical biosensor based on the exciton energy transfer constructed for theophylline detection.

A novel photoelectrochemical (PEC) biosensor was developed incorporating a specifically designed RNA aptamer for the detection of theophylline (TP). This involved utilizing two nucleotide base aptamers with tailored sequences designed to target TP. The 3' end of a single-stranded RNA sequence (5'-GGAUACCA-(CH2)6-SH-3') and the 5' end of a complementary stranded RNA sequence (5'-HS-(CH2)6-CCUUGGAAGCC-3') were linked to gold nanoparticles (AuNPs) and CdS quantum dots (QDs), respectively. These two single-stranded RNAs (ssRNA) formed a double-stranded RNA (dsRNA) capable of recognizing TP. This major structural change altered the spacing between QDs and NPs, which signaled the presence and concentration of TP. TP was photoelectrochemical catalytic oxidation by the hole of CdS QDs under illumination, then anode photocurrent was generated. Due to the increase in surface impedance and the effect of exciton energy transfer (EET) between QDs and AuNPs, the photocurrent would undergo varying degrees of change. TP was detected by changes in photocurrent. PEC detection of TP was achieved in the range of 0.1 µM-200 µM. The detection limit was 0.033 µM. The method exhibited commendable reproducibility and remarkable selectivity. The biosensor was used to measure TP content in tea, beverages and blood samples, resulting in satisfactory recovery rates.

CircZNF609 promotes bladder cancer progression and inhibits cisplatin sensitivity via miR-1200/CDC25B pathway.

Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 (hsa_circ_0000615) has been shown to serve as an oncogene in all kinds of solid tumors and may act as the novel biomarker in tumor diagnosis and therapy in tumor early diagnosis and therapy. However, the underlying character and mechanism of circZNF609 in cisplatin chemosensitivity and bladder cancer (BCa) development were unknown. The expression level of cell division cycle 25B (CDC25B), microRNA 1200 (miR-1200), and circZNF609 in BCa cells and tissues depended on quantitative real-time PCR (qRT-PCR). CDC25B protein level was assayed with Western blot. Functional assays in vitro and in vivo had been conducted to inspect the important role of circZNF609 on BCa progression and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200, and CDC25B. Mechanistic exploration was confirmed by RNA pull-down assay, RNA fluorescence in situ hybridization (FISH) and Dual luciferase reporter assay. CircZNF609 expression was increased significantly in BCa cell lines and tissues. For BCa patients, increased expression of circZNF609 was correlated with a worse survival. In vitro and in vivo, enforced expression of circZNF609 enhanced BCa cells proliferation, migration, and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to act as a new diagnostic biomarker and therapeutic target in BCa. Enhancing cisplatin sensitivity is an important direction for bladder cancer management. 1. This research reveals that circZNF609 improves bladder cancer progression and inhibits cisplatin sensitivity by inducing G1/S cell cycle arrest via a novel miR-1200/CDC25B cascades. 2. CircZNF609 was confirmed associated with worse survival of bladder cancer patients. 3. CircZNF609 act as a prognostic biomarker for bladder cancer treatment.

External validation of Pentafecta in patients undergoing laparoscopic radical cystectomy: results from a high-volume center.

BACKGROUND: To investigate whether Pentafecta is suitable for bladder cancer patients receiving laparoscopic radical cystectomy (LRC). METHODS: From November 2013 to December 2020, muscle invasive Bladder Cancer (MIBC) and non-muscle invasive Bladder Cancer (NMIBC) patients who received LRC and urinary diversion were retrospectively analyzed. Pentafecta was defined as meeting five criteria: negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year. Analyze the achievement of five criteria and compare the overall survival (OS) of Pentafecta group with non-attainment group. Multivariable Cox's regression was performed to evaluate the impact of Pentafecta on OS. Multivariable logistic regression was performed to explore the effect of surgical experience on Pentafecta attainment. RESULTS: A total of 340 patients were included, negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year were observed in 95.3%, 30.3%, 83.8%, 75.0% and 85.6% of patients, respectively. Pentafecta group had a significantly longer OS than the non-attainment group (P = 0.027). The group with 10-15 LNs removed and meeting the other four criteria had a similar OS to group with ≥ 16 LNs removed (Pentafecta group) (5-year OS: 67.3% vs 72.7%, P = 0.861). Pentafecta (HR = 0.33, P = 0.011), positive lymph nodes (HR = 2.08, P = 0.028) and MIBC (HR = 3.70, P < 0.001) were all significant predictors of OS in multivariable Cox's regression. Surgical experience (OR = 1.05, P < 0.001), conduit (OR = 2.09, P = 0.047) and neobladder (OR = 2.47, P = 0.048) were all independent predictors of Pentafecta attainment in multivariable logistic regression. CONCLUSIONS: Pentafecta is suitable for bladder cancer patients receiving LRC and has the potential to be a valuable tool for evaluating the quality of LRC. Based on Pentafecta analysis, removing 10 LNs instead of 16 LNs as the one of the five criteria may be more appropriate for bladder cancer patients.

The application value of multi-parameter cystoscope in improving the accuracy of preoperative bladder cancer grading.

PURPOSE: To develop and validate a preoperative cystoscopic-based predictive model for predicting postoperative high-grade bladder cancer (BCa), which could be used to guide the surgical selection and postoperative treatment strategies. MATERIALS AND METHODS: We retrospectively recruited 366 patients with cystoscopy biopsy for pathology and morphology evaluation between October 2010 and January 2021. A binary logistic regression model was used to assess the risk factors for postoperative high-grade BCa. Diagnostic performance was analyzed by plotting receiver operating characteristic curve and calculating area under the curve (AUC), sensitivity, specificity. From January 2021 to July 2021, we collected 105 BCa prospectively to validate the model's accuracy. RESULTS: A total of 366 individuals who underwent transurethral resection of bladder tumor (TURBT) or radical cystectomy following cystoscopy biopsy were included for analysis. 261 (71.3%) had a biopsy pathology grade that was consistent with postoperative pathology grade. We discovered five cystoscopic parameters, including tumor diameter, site, non-pedicled, high-grade biopsy pathology, morphology, were associated with high-grade BCa. The established multi-parameter logistic regression model ("JSPH" model) revealed AUC was 0.917 (P < 0.001). Sensitivity and specificity were 86.2% and 84.0%, respectively. And the consistency of pre- and post-operative high-grade pathology was improved from biopsy-based 70.5% to JSPH model-based 85.2%. In a 105-patients prospective validation cohort, the consistency of pre- and post-operative high-grade pathology was increased from 63.1 to 84.2% after incorporation into JSPH model for prediction. CONCLUSION: The cystoscopic parameters based "JSPH model" is accurate at predicting postoperative pathological high-grade tumors prior to operations.

Robot-Assisted Laparoscopic Retroperitoneal Renal Artery Aneurysm Repair: A Rare Case Report and Literature Review.

INTRODUCTION: The treatment of renal artery aneurysms (RAAs) includes surgical repair and endovascular techniques. Surgical repair is divided into open surgery repair and laparoscopic surgery repair. Laparoscopic RAA has fewer postoperative complications than open surgery. Some experiences with robotic RAA repair via transperitoneal access have been recently reported. However, no report could be found on the treatment of retroperitoneal RAA with the da Vinci robot-assisted surgery thus far. CASE PRESENTATION: Here, the surgical management of an 8.6-mm right-sided RAA via robot-assisted laparoscopic retroperitoneal approach in a 58-year-old man who presented with flank discomfort is reported. The aneurysm was resected, and the renal artery was reconstructed. The total operative time was 2 h with a warm ischemia time of 25 min, and the estimated surgical blood loss was 50 mL. The patient resumed a regular diet on postoperative day 2, and the hospital stay lasted 5 days. No intraoperative nor postoperative morbidity was reported. Follow-up imaging and functional analysis demonstrated resolution of the aneurysm and preservation of renal function after 2.5 months. CONCLUSIONS: Robot-assisted laparoscopic retroperitoneal RAA repair is flexible and safe. The greatest advantage of retroperitoneal surgery is direct access to the renal artery. Furthermore, it could reduce the injury in the abdominal organs and avoid abdominal adhesion. This approach may also allow for improved postoperative recovery, reduce the morbidity correlated with transperitoneal RAA, and thus may be considered as an alternative to transperitoneal surgery for RAAs in the future.

Mechanism of RNA modification N6-methyladenosine in human cancer.

Since the breakthrough discoveries of DNA and histone modifications, the field of RNA modifications has gained increasing interest in the scientific community. The discovery of N6-methyladenosine (m6A), a predominantly internal epigenetic modification in eukaryotes mRNA, heralded the creation of the field of epi-transcriptomics. This post-transcriptional RNA modification is dynamic and reversible, and is regulated by methylases, demethylases and proteins that preferentially recognize m6A modifications. Altered m6A levels affect RNA processing, degradation and translation, thereby disrupting gene expression and key cellular processes, ultimately resulting in tumor initiation and progression. Furthermore, inhibitors and regulators of m6A-related factors have been explored as therapeutic approaches for treating cancer. In the present review, the mechanisms of m6A RNA modification, the clinicopathological relevance of m6A alterations, the type and frequency of alterations and the multiple functions it regulates in different types of cancer are discussed.

Simultaneous detection of two tumor markers using silver and gold nanoparticles decorated carbon nanospheres as labels.

In this work, a multiplexed electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) using silver nanoparticles (Ag NPs) or gold nanoparticles (Au NPs) coated-carbon nanospheres (CNSs) as labels. CNSs were employed as the carrier for the immobilization of nanoparticles (Ag NPs or Au NPs), thionine (Thi), and secondary antibodies (Ab2) due to their good monodispersity and uniform structure. Au NPs reduced graphene oxide (rGO) nanocomposites were used as sensing substrate for assembling two primary antibodies (Ab1). In the presence of target proteins, two labels were attached onto the surface of the rGO/Au NPs nanocomposites via a sandwich immunoreaction. Two distinguishable peaks, one at +0.16 V (corresponding to Ag NPs) and another at -0.33 V (corresponding to Thi), were obtained in differential pulse voltammetry (DPV). The peak difference was approximately 490 mV, indicating that CEA and AFP can be simultaneously detected in a single run. Under optimal conditions, the peak currents were linearly related to the concentrations of CEA or AFP in the range of 0.01-80 ng ml(-1). The detection limits of CEA and AFP were 2.8 and 3.5 pg ml(-1), respectively (at a signal-to-noise ratio of 3). Moreover, when the immunosensor was applied to serum samples, the results obtained were in agreement with those of the reference method, indicating that the immunosensor would be promising in the application of clinical diagnosis and screening of biomarkers.

Simultaneous electrochemical detection of multiple biomarkers using gold nanoparticles decorated multiwall carbon nanotubes as signal enhancers.

In this work, a novel sandwich-type electrochemical immunosensor has been developed for simultaneous detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) based on metal ion labels. Gold nanoparticles decorated multiwall carbon nanotubes (AuNPs@MWCNTs) were used as carriers to immobilize secondary antibodies and distinguishable electrochemical tags of Pb(2+) and Cd(2+) to amplify the signals. Due to the intrinsic property of high surface-to-volume ratio, the AuNPs@MWCNTs could load numerous secondary antibodies and labels. Therefore, the multiplexed immunoassay exhibited good sensitivity and selectivity. Experimental results revealed that this sandwich-type immunoassay displayed an excellent linear response, with a linear range of 0.01 to 60 ng mL(-1) for both analytes and detection limits of 3.0 pg mL(-1) for CEA and 4.5 pg mL(-1) for AFP (at a signal-to-noise ratio of 3). The method was successfully applied for the determination of AFP and CEA levels in clinical serum samples.

Optimized Bionic Drug-Delivery-Inducing Immunogenic Cell Death and cGAS-STING Pathway Activation for Enhanced Photodynamic-Chemotherapy-Driven Immunotherapy in Prostate Cancer.

Prostate cancer presents as a challenging disease, as it is often characterized as an immunologically "cold" tumor, leading to suboptimal outcomes with current immunotherapeutic approaches in clinical settings. Photodynamic therapy (PDT) harnesses reactive oxygen species generated by photosensitizers (PSs) to disrupt the intracellular redox equilibrium. This process induces DNA damage in both the mitochondria and nucleus, activating the process of immunogenic cell death (ICD) and the cGAS-STING pathway. Ultimately, this cascade of events leads to the initiation of antitumor immune responses. Nevertheless, existing PSs face challenges, including suboptimal tumor targeting, aggregation-induced quenching, and insufficient oxygen levels in the tumor regions. To this end, a versatile bionic nanoplatform has been designed for the simultaneous delivery of the aggregation-induced emission PS TPAQ-Py-PF6 and paclitaxel (PTX). The cell membrane camouflage of the nanoplatform leads to its remarkable abilities in tumor targeting and cellular internalization. Upon laser irradiation, the utilization of TPAQ-Py-PF6 in conjunction with PTX showcases a notable and enhanced synergistic antitumor impact. Additionally, the nanoplatform has the capability of initiating the cGAS-STING pathway, leading to the generation of cytokines. The presence of damage-associated molecular patterns induced by ICD collaborates with these aforementioned cytokines lead to the recruitment and facilitation of dendritic cell maturation. Consequently, this elicits a systemic immune response against tumors. In summary, this promising strategy highlights the use of a multifunctional biomimetic nanoplatform, combining chemotherapy, PDT, and immunotherapy to enhance the effectiveness of antitumor treatment.

Transformable Supramolecular Self-Assembled Peptides for Cascade Self-Enhanced Ferroptosis Primed Cancer Immunotherapy.

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy.

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.

Dietary N-carbamylglutamate supplementation improves ammonia tolerance of juvenile yellow catfish Pelteobagrus fulvidraco.

Introduction: Ammonia has been of concern for its high toxicity to animals. N-carbamylglutamate (NCG) can reduce blood ammonia levels in mammals, but studies on ammonia tolerance in fish are insufficient. Methods: Juvenile yellow catfish were fed two levels of NCG (0.00% and 0.05%) for 84 days under three ammonia levels (0.00, 0.08, and 0.16 mg/L NH3). Results and Discussion: The results showed that survival rate (SUR), final body weight (FBW), weight gain (WG), and serum total protein (TP), triglycerides (TG), glucose (Glu), ornithine (Orn), citrulline (Cit) contents, and liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), arginase (ARG), ornithine transcarbamylase (OTC) activities decreased with the increase of ammonia levels, on the contrary, feed conversion ratio (FCR), hepatosomatic index (HSI), and serum ammonia, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine (Gln), arginine (Arg) contents, and liver malondialdehyde (MDA), tumor necrosis factor (TNF), interleukin (IL) 1, IL 8 contents, and mRNA expressions of cu/zn sod, cat, gpx, gr, tnf ɑ, il 1, and il 8 were significantly increased. Dietary 0.05% NCG supplementation had higher SUR, FBW, WG, feed intake (FI), whole-body protein, and serum TP, total cholesterol (TC), Glu, citrulline (Cit) contents, and liver SOD, GPx, argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), inducible nitric oxide synthase (iNOS) activities compared to 0.00% NCG group, but had lower serum ammonia, urea, ALT, AST, Gln, Arg contents, and liver MDA, TNF, IL 1, IL 8 contents, and neuronal nitric oxide synthase activity. At the end of bacterial challenge, cumulative mortality (CM) increased with ammonia levels increased, but serum antibody titer (AT), lysozyme (LYZ) activity, 50% hemolytic complement, immunoglobulin (Ig) contents, respiratory burst (RB), phagocytic indices decreased with ammonia levels increased. CM in 0.05% NCG group was lower than that in 0.00% NCG group, but serum AT, LYZ activity, Ig content, RB in 0.05% NCG group were significantly higher. The correlation analysis found that iNOS was positively correlated with ASS activity. This study indicates that dietary NCG supplementation can improve the ammonia tolerance of yellow catfish, and ASS may also be the target of NCG to activate the urea cycle.

Pan-cancer analysis reveals the prognostic gene CASR suppresses tumor progression and epithelial-mesenchymal transition in renal clear cell carcinoma.

Calcium-sensing receptor (CASR), primarily found in the parathyroid gland and other tissues, plays a crucial role in sensing and regulating extracellular calcium, which was also aberrantly expressed in human tumors. Nevertheless, a comprehensive analysis of CASR in pan-cancer has yet to be conducted. To gain a better understanding of CASR in pan-cancer, data profiles on CASR cancers were collected from TCGA database. The expression level, clinical significance, prognostic value, and potential mechanisms of CASR in pan-cancer were analyzed via multiple public databases. The functional assays were conducted using human kidney renal clear cell carcinoma (KIRC) cell lines, clinical samples, and nude mice. Our research revealed that the abnormal expression of CASR was found in a variety of tumors. The expression and mutation of CASR were significantly associated with tumor prognosis and stage. Pathway analyses suggested that CASR was involved in the epithelial-mesenchymal transition (EMT) progress. Besides, CASR expression was correlated with immune inhibitory genes and immunotherapy in cancers. Particularly in KIRC, we established that CASR mRNA and protein levels were downregulated in clinical samples and cell lines. Moreover, a Cox regression analysis revealed that CASR was an independent prognostic factor in both TCGA-KIRC samples and clinical samples from our center. In vitro and in vivo experiments revealed that blocking CASR with lentivirus could suppress tumor growth and invasion, and EMT progress in KIRC cells. In summary, our study provides a comprehensive bioinformatic analysis of CASR in pan-cancer, offering deeper insights into its function and the EMT mechanism in KIRC, warranting further investigation.

Untargeted and targeted metabolomics reveal bile acid profile changes in rats with ethylene glycol-induced calcium oxalate nephrolithiasis.

Calcium oxalate (CaOx) nephrolithiasis is a prevalent disorder linked to metabolism. Examining metabolic alterations could potentially give an initial understanding of the origins of CaOx nephrolithiasis. This study aims to determine gut metabolic biomarkers differentiating CaOx nephrolithiasis utilizing untargeted and targeted metabolomics. CaOx nephrolithiasis model rats were built by 1% ethylene glycol administration. Histologic staining and renal function measurement revealed the presence of crystals in the lumen of the renal tubules, the renal injury and interstitial fibrosis in CaOx rats, demonstrating that the models of CaOx were established successfully. Hematoxylin & eosin (H&E) staining showed that CaOx group had inflammation and damage in the ileal tissue. Immunofluorescence and PCR results displayed that the tight junction proteins, ZO-1 and Occludin levels were decreased in the ileal tissues of the CaOx group. The untargeted metabolomic analysis revealed that 269 gut metabolites were differentially expressed between the CaOx group and the control group. Meanwhile, bile secretion, the main metabolic pathway in CaOx nephrolithiasis, was identified. Following, five significant bile acid metabolites were selected utilizing the targeted bile acid metabolomics, including Hyodeoxycholic acid (HDCA), Glycohyodeoxycholic acid (GHDCA), Nor-Deoxycholic Acid, omega-muricholic acid, and Taurolithocholic acid. Among these metabolites, HDCA and GHDCA presented the highest predictive accuracy with AUC = 1 to distinguish the CaOx group from the control group. As a result of network pharmacology, target genes of HDCA and GHDCA in CaOx nephrolithiasis were enriched in oxidative stress and apoptosis pathways. Conclusively, our study provides insight into bile acids metabolic changes related to CaOx nephrolithiasis. Although alterations in biochemical pathways indicate a complex pathology in CaOx rats, bile acid changes may serve as biomarkers of CaOx nephrolithiasis.

Effects of dietary leucine on growth, antioxidant capacity, immune response, and inflammation in juvenile yellow catfish Pelteobagrus fulvidraco.

The experiment was conducted to investigate the effects of dietary leucine on growth, antioxidant capacity, immune response, and inflammation in juvenile yellow catfish. Five diets were formulated to contain five dietary leucine levels: 12.00 (control), 19.00, 26.00, 33.00, and 40.00 g kg-1. Each diet was randomly assigned to triplicate groups of 30 juvenile fish (5.02 ± 0.15 g) twice daily to apparent satiation for 56 days. Weight gain rate, specific growth rate, and activities of liver superoxide dismutase, glutathione peroxidase, and serum lysozyme, as well as immunoglobulin M content, significantly increased with increase in dietary leucine levels up to 26.00 g kg-1, but those values decreased significantly with a further increase in dietary leucine. On the contrary, the lowest malondialdehyde content was found in 26.00 and 33.00 g kg-1 leucine groups. The expression levels of IGF 1 and MYF 5 genes in muscle were significantly upregulated with increase in dietary leucine levels up to 26.00 g kg-1, but the expression of MSTN level showed the opposite trend. The lowest expression levels of IL 8 and TNFɑ genes in the liver were found in 26.00 g kg-1 leucine groups. The quadratic regression analysis on weight gain, specific growth rate, and feed conversion ratio against dietary leucine levels indicated that the optimal dietary leucine requirement was estimated to be 26.84-27.00 g kg-1of the dry diet.

Dual-Pronged Attack: pH-Driven Membrane-Anchored NIR Dual-Type Nano-Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo-Immunotherapy.

Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T-lymphocyte infiltration, and convert tumors from "cold" to "hot." However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD-L1 caused by photo-immunotherapy further promotes immune escape. Herein, a new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH-responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near-infrared-activated semiconductor polymer photosensitizer YBS and a PD-1/PD-L1 complex small molecule inhibitor BMS-202. The pH-driven membrane-anchoring and pyroptosis activation of YBS-BMS NPs-RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual-pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long-term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self-synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo-controlled pyroptosis inducers.

Highly Sensitive Immunosensing of Carcinoembryonic Antigen Based on Gold Nanoparticles Dotted PB@PANI Core-Shell Nanocubes as a Signal Probe.

Herein, a method was developed for the sensitive monitoring of carcinoembryonic antigen (CEA) by gold nanoparticles dotted prussian blue@polyaniline core-shell nanocubes (Au NPs/PB@PANI). First, a facile low-temperature method was used to prepare the uniform PB@PANI core-shell nanocubes with the assistance of PVP, where PB acted as the electron transfer mediator to provide electrochemical signals, and the PANI with excellent conductivity and desirable chemical stability not only played the role of a protective layer to prevent etching of PB in basic media but also effectively improved electron transfer. Importantly, to further enhance the electrical conductivity and biocompatibility of PB@PANI and to further enhance the electrochemical signal and capture a large amount of Ab2, Au NPs were doped on the surface of PB@PANI to form Au NPs/PB@PANI nanocomposites. Subsequently, benefiting from the advantages of core-shell structure nanoprobes and gold-platinum bimetallic nanoflower (AuPt NF), a sandwich-type electrochemical immunosensor for CEA detection was constructed, which provided a wide linear detection range from 1.0 pg·mL-1 to 100.0 ng·mL-1 and a low detection limit of 0.35 pg·mL-1 via DPV (at 3σ). Moreover, it displayed a satisfactory result when the core-shell structure nanoprobe-based immunosensor was applied to determine CEA in real human serum samples.

The combination of highly efficient resonance energy transfer in one nanocomposite and ferrocene-quenching for ultrasensitive electrochemiluminescence bioanalysis.

Sensitive and accurate detection of prostate-specific antigen (PSA) is of great significance since it is regarded as a biomarker for prostate diseases. Herein, a facile strategy for the design of highly efficient electrochemiluminescence (ECL) sensor was proposed for PSA assay. Carboxylated graphitic carbon nitride (g-C3N4) nanosheet (CCN) and tris (2, 2'-Bipyridyl) ruthenium (II) (Ru(bpy)32+) encapsulated in silica nanospheres (RuSi NPs) were employed as the donor and acceptor, respectively. CCN and RuSi NPs were covalently bound within one nanocomposite (CCN@RuSi) through the amide bond, which greatly shortened the electron-transfer path. Thus, the resonance energy transfer (RET) efficiency was remarkably increased, providing a high initial ECL intensity for the ECL assay. After the successive introducing of aptamer, PSA, and ferroceneboronic acid (FcBA) on the surface of CCN@RuSi modified electrode, the ECL signal remarkably decreased, which was caused by the steric hindrance of PSA and electron transfer quenching between Fc+ and excited-state Ru(bpy)32+*. Therefore, a highly efficient ECL platform was constructed, which achieved the ultrasensitive detection of PSA with a linear range and a limit of detection of 100 fg/mL - 50 ng/mL and 1.2 fg/mL, respectively. Furthermore, the dual-affinity of the aptamer and FcBA to PSA endowed the sensor with a high selectivity for the determination of PSA in human serum samples. The present work provides an important reference for the integration of RET and quenching strategy in the ECL study with rapid, ultrasensitive, and highly selective detection performances.

A Sensitive Fluorescent Immunoassay for Prostate Specific Antigen Detection Based on Signal Amplify Strategy of Horseradish Peroxidase and Silicon Dioxide Nanospheres.

A simple, sensitive, and fluorescent immunoassay for the detection of prostate-specific antigen (PSA) based on horseradish peroxidase and silicon dioxide nanospheres as a signal amplification strategy has been described. In the design, the primary antibody (Ab1) of PSA was first immobilized on the 96-well plates via physical adsorption between polystyrene and hydrophobic groups of the antibody molecule. The silicon dioxide nanospheres (SiO2 NSs), with large surface area and good biocompatibility, were loaded with horseradish peroxidase (HRP) and horseradish peroxidase-labeled secondary antibodies (HRP-Ab2) as signal amplification systems. In the presence of PSA, a sandwich-type immunocomplex composed of Ab1-Ag-HRP-Ab2 had been formed. Fluorescence technology was employed to obtain the response signal of the immunoassay in the L-tyrosine and H2O2 systems. Experiment results showed that a strong and stable fluorescent signal at 416 nm (excitation wavelength: 325 nm) was observed, and the changes in fluorescent intensity were related to the levels of PSA. Under the optimal conditions, the relative fluorescence intensity was linear with the logarithm of PSA concentration from 0.03 to 100 ng·mL-1, with a detection limit of 0.01 ng·mL-1 (at a signal/noise ratio of 3). In contrast to other fluorescent immunoassays, the sandwich-type immunoreaction based on the high binding ELISA plates has the advantages of being simple, stable, and easy to operate, high selectivity, small sample quantity, etc., which can be widely used in the selective detection of a variety of targets, from DNA to proteins and small molecules. Such fluorescent immunoassays should be feasible for the fields of molecular diagnosis and other life science fields in the future.