Exploring the versatility of biodegradable biomass aerogels: In-depth evaluation of Firmiana simplex bark microfibers depolymerized by deep eutectic solvent.

In this study, we investigated the use of deep eutectic solvents (DESs) at different molar ratios and temperatures as a green and efficient approach for microfibers (MFs) extraction. Our approach entailed the utilization of Firmiana simplex bark (FSB) fibers, enabling the production of different dimensions of FSB microfibers (FSBMFs) by combining DES pretreatment and mechanical disintegration technique. The proposed practice demonstrates the simplicity and effectiveness of the method. The morphology of the prepared microfibers was studied using the Scanning electron microscopic (SEM) technique. Additionally, the results revealed that the chemical and mechanical treatments did not significantly alter the well-preserved cellulose structure of microfibers, and a crystallinity index of 56.6 % for FSB fibers and 63.8 % for FSBMFs was observed by X-ray diffraction (XRD) analysis. Furthermore, using the freeze-drying technique, FSBMFs in water solutions produced effective aerogels for air purification application. In comparison to commercial mask (CM), FSBMF aerogels' superior hierarchical cellular architectures allowed them to attain excellent filtration efficiencies of 94.48 % (PM10) and 91.51 % (PM2.5) as well as excellent degradation properties were analyzed. The findings show that FSBMFs can be extracted from Firmiana simplex bark, a natural cellulose-rich material, using DES for environmentally friendly aerogel preparation and applications.

METTL16 suppressed the proliferation and cisplatin-chemoresistance of bladder cancer by degrading PMEPA1 mRNA in a m6A manner through autophagy pathway.

N6-methyladenosine (m6A) is important in the physiological processes of many species. Methyltransferase-like 16 (METTL16) is a novel discovered m6A methylase, regulating various tumors in an m6A-dependent manner. However, its function in bladder cancer (BLCA) remains largely unclear. In the present study, we found that low expression of METTL16 predicted poor survival in BLCA patients. METTL16 inhibited the proliferation and cisplatin-resistance function of bladder cancer cells in vitro and in vivo. In addition, METTL16 reduced the mRNA stability of prostate transmembrane protein androgen induced-1 (PMEPA1) via binding to its m6A site in the 3'-UTR, thereby inhibited the proliferation of bladder cancer cells and increased the sensitivity of cisplatin through PMEPA1-mediated autophagy pathway. Finally, we found that hypoxia-inducible factor 2α (HIF-2α) exerted its tumor-promoting effect by binding the METTL16 promoter region to repress its transcription. Taken together, High expression of METTL16 predicted better survival in BLCA. METTL16 significantly inhibited bladder cancer cell proliferation and sensitized bladder cancer cells to cisplatin via HIF-2α-METTL16-PMEPA1-autophagy axis in a m6A manner. These findings might provide fresh insights into BLCA therapy.

Versatile, durable conductive networks assembled from MXene and sericin-modified carbon nanotube on polylactic acid textile micro-etched via deep eutectic solvent.

Integration of polylactic acid (PLA) textiles with conductive MXene holds great promise for fabricating green electronic textiles (e-textiles) and reducing the risk of electronic waste. However, constructing robust conductive networks on PLA fibers remains challenging due to the susceptibility of MXene to oxidation and the hydrophobicity of PLA fibers. Here, we demonstrate a versatile, degradable, and durable e-textile by decorating the deep eutectic solvent (DES) micro-etched PLA textile with MXene and sericin-modified carbon nanotube hybrid (MXene@SSCNT). The co-assembly of MXene with SSCNT in water not only enhanced its oxidative stability but also formed synergistic conductive networks with biomimetic leaf-like nanostructures on PLA fiber. Consequently, the MXene@SSCNT coated PLA textile (MCP-textile) exhibited high electrical conductivity (5.5 Ω·sq-1), high electromagnetic interference (EMI) shielding efficiency (34.20 dB over X-band), excellent electrical heating performance (66.8 ℃, 5 V), and sensitive humidity response. Importantly, the interfacial bonding between the MXene@SSCNT and fibers was significantly enhanced by DES micro-etching, resulting in superior wash durability of MCP-textile. Furthermore, the MCP-textile also showed satisfactory breathability, flame retardancy, and degradability. Given these outstanding features, MCP-textile can serve as a green and versatile e-textile with tremendous potential in EMI shielding, personal thermal management, and respiratory monitoring.

Stable and oxidative charged Ru enhance the acidic oxygen evolution reaction activity in two-dimensional ruthenium-iridium oxide.

The oxygen evolution reactions in acid play an important role in multiple energy storage devices. The practical promising Ru-Ir based catalysts need both the stable high oxidation state of the Ru centers and the high stability of these Ru species. Here, we report stable and oxidative charged Ru in two-dimensional ruthenium-iridium oxide enhances the activity. The Ru0.5Ir0.5O2 catalyst shows high activity in acid with a low overpotential of 151 mV at 10 mA cm-2, a high turnover frequency of 6.84 s-1 at 1.44 V versus reversible hydrogen electrode and good stability (618.3 h operation). Ru0.5Ir0.5O2 catalysts can form more Ru active sites with high oxidation states at lower applied voltages after Ir incorporation, which is confirmed by the pulse voltage induced current method. Also, The X-ray absorption spectroscopy data shows that the Ru-O-Ir local structure in two-dimensional Ru0.5Ir0.5O2 solid solution improved the stability of these Ru centers.

Hsa_circ_0003098 promotes bladder cancer progression via miR-377-5p/ACAT2 axis.

Accumulating evidence has proven that circRNAs play vital roles in tumor progression. Nevertheless, the mechanisms underlying circRNAs in bladder cancer (BCa) remain largely unknown. The purpose of this study was to identify the role and investigate the potential molecular mechanisms of hsa_circ_0003098 in BCa. We confirmed that hsa_circ_0003098 expression was significantly upregulated in BCa tissues, of which expression was remarkably associated with poor prognosis. Functionally, overexpression of hsa_circ_0003098 promoted BCa cell proliferation, migration, and invasion in vitro as well as tumor growth in vivo. Mechanistically, hsa_circ_0003098 promoted upregulation of ACAT2 expression and induced cholesteryl ester accumulation via acting as a sponge for miR-377-5p. Thus, hsa_circ_0003098 plays an oncogenic role in BCa and may serve as a potential biomarker and therapeutic target for BCa.

Superhydrophilicity boron-doped cobalt phosphide nanosheets decorated carbon nanotube arrays self-supported electrode for overall water splitting.

Transition metal borides (TMBs) or phosphides (TMPs) have attracted great attention to the design of bifunctional electrocatalysts for energy storage. The superaerophobicity and superhydrophilicity of the catalytic electrode surface are crucial factors to determine the reaction process of the gas electrode. Herein, we report a self-supported electrode of carbon nanotube (CNTs) array grown on carbon cloth (CC) modulated together by boron-doped cobalt phosphide (CoP-B/CNTs/CC). The electrode requires the overpotential of 73.8 mV and 189.5 mV at the current density of ±10 mA cm-2 for hydrogen and oxygen evolution reactions in an alkaline electrolyte (1.0 M KOH), respectively, meanwhile maintaining outstanding long-term durability for more than 300 h. The excellent activity of CoP-B/CNTs/CC is attributed to boron doping regulating its electronic structure and further enriching active sites. The attractive stability of CoP-B/CNTs/CC is due to the unique geometric structure of the self-supported electrode. Furthermore, the superaerophobicity and superhydrophilicity of the electrode surface also accelerate the reaction process of the gas electrode. Expectedly, water splitting cells assembled using CoP-B/CNTs/CC electrodes as cathode and anode, respectively, require a cell voltage of 1.54 V at 10 mA cm-2, which is lower than that of the Pt/C/CC||RuO2/CC couple (1.69 V at 10 mA cm-2). Importantly, CoP-B/CNTs/CC||CoP-B/CNTs/CC achieve stable cell voltage under the step current changes (10 mA cm-2, 50 mA cm-2, and 100 mA cm-2) over 300 h. This work highlights a new path to understanding the effects of the static and dynamic behavior of bubbles on the surface of self-supporting electrodes on catalytic performance.

Lysine N-methyltransferase SETD7 promotes bladder cancer progression and immune escape via STAT3/PD-L1 cascade.

Background: The immunotherapy sensitivity of patients with bladder cancer (BCa) remains low. As the role of protein methylation in tumorigenesis and development becomes clearer, the role of lysine N-methyltransferase SET domain containing 7 (SETD7) in the progression and immune escape of BCa is worth studying. Methods: The correlation between lysine methyltransferase family and prognosis or immunotheray sensitivity of BCa patients were analyzed, and SETD7 was screened out because of the significant correlation between its expression and survival data or immunotherapy sensitivity. The expression of SETD7 in BCa tissues and cell lines were explored. The functions of SETD7 were investigated by proliferation and migration assays. The role of SETD7 in BCa immune escape was validated by analyzing the correlation between SETD7 expression and tumor microenvironment (TME)-related indicators. The results were further confirmed by conducting BCa cell-CD8+ T cell co-culture assays and tumorigenesis experiment in human immune reconstitution NOG mice (HuNOG mice). Bioinformatic prediction, CO-IP, qRT-PCR, and western blot were used to validate the SETD7/STAT3/PD-L1 cascade. Results: SETD7 was highly expressed in BCa, and it was positively associated with high histological grade and worse prognosis. SETD7 promoted the proliferation and migration of BCa cells. The results of bioinformatics, in vitro co-culture, and in vivo tumorigenesis assays showed that SETD7 could inhibit the chemotoxis and cytotoxicity of CD8+ T cells in BCa TME. Mechanistically, bioinformatics analysis, CO-IP assay, qRT-PCR, and western blot results indicated that SETD7 could increase the expression of PD-L1 via binding and promoting STAT3. Conclusions: Taken together, SETD7 indicated poor prognosis and promoted the progression and immune escape of BCa cells. It has great potential to act as a new indicator for BCa diagnosis and treatment, especially immunotherapy.

Clinical significance, tumor immune landscape and immunotherapy responses of ADAR in pan-cancer and its association with proliferation and metastasis of bladder cancer.

BACKGROUND: ADAR is an enzyme involved in adenosine-inosine RNA editing. However, the role of ADAR in tumorigenesis, progression, and immunotherapy has not been fully elucidated. METHODS: The TCGA, GTEx and GEO databases were extensively utilized to explore the expression level of ADAR across cancers. Combined with the clinical information of patients, the risk profile of ADAR in various cancers was delineated. We identified pathways enriched in ADAR and their related genes and explored the association between ADAR expression and the cancer immune microenvironment score and response to immunotherapy. Finally, we specifically explored the potential value of ADAR in the treatment of the bladder cancer immune response and verified the critical role of ADAR in the development and progression of bladder cancer through experiments. RESULTS: ADAR is highly expressed in most cancers at both the RNA and protein level. ADAR is associated with the aggressiveness of some cancers, especially bladder cancer. In addition, ADAR is associated with immune-related genes, especially immune checkpoint genes, in the tumor immune microenvironment. Moreover, ADAR expression is positively correlated with tumor mutation burden and microsatellite instability in a variety of cancers, indicating that ADAR could be used as a biomarker of immunotherapy. Finally, we demonstrated that ADAR is a key pathogenic factor in bladder cancer. ADAR promoted proliferation and metastasis of bladder cancer cells. CONCLUSION: ADAR regulates the tumor immune microenvironment and can be used as a biomarker of the tumor immunotherapy response, providing a novel strategy for the treatment of tumors, especially bladder cancer.

HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway.

BACKGROUND: The response rate to immunotherapy in patients with bladder cancer (BCa) remains relatively low. Considering the stable existence and important functions in tumour metabolism, the role of circRNAs in regulating immune escape and immunotherapy sensitivity is receiving increasing attention. METHODS: Circular RNA (circRNA) sequencing was performed on five pairs of BCa samples, and circFAM13B (hsa_circ_0001535) was screened out because of its remarkably low expression in BCa. Further mRNA sequencing was conducted, and the association of circFAM13B with glycolysis process and CD8+ T cell activation was confirmed. The functions of circFAM13B were verified by proliferation assays, glycolysis assays, BCa cells-CD8+ T cell co-culture assays and tumorigenesis experiment among human immune reconstitution NOG mice. Bioinformatic analysis, RNA-protein pull down, mass spectrometry, RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were performed to validate the HNRNPL/circFAM13B/IGF2BP1/PKM2 cascade. RESULTS: Low expression of circFAM13B was observed in BCa, and it was positively associated with lower tumour stage and better prognosis among patients with BCa. The function of CD8+ T cells was promoted by circFAM13B, and it could attenuate the glycolysis of BCa cells and reverse the acidic tumour microenvironment (TME). The production of granzyme B and IFN-γ was improved, and the immunotherapy (PD-1 antibodies) sensitivity was facilitated by the inhibition of acidic TME. Mechanistically, circFAM13B was competitively bound to the KH3-4 domains of IGF2BP1 and subsequently reduced the binding of IGF2BP1 and PKM2 3'UTR. Thus, the stability of the PKM2 mRNA decreased, and glycolysis-induced acidic TME was inhibited. The generation of circFAM13B was explored by confirming whether heterogeneous nuclear ribonucleoprotein L (HNRNPL) could promote circFAM13B formation via pre-mRNA back-splicing. CONCLUSIONS: HNRNPL-induced circFAM13B could repress immune evasion and enhance immunotherapy sensitivity by inhibiting glycolysis and acidic TME in BCa through the novel circFAM13B/IGF2BP1/PKM2 cascade. Therefore, circFAM13B can be used as a biomarker for guiding the immunotherapy among patients with BCa.

In silico, in vitro and in vivo studies: Dibutyl phthalate promotes prostate cancer cell proliferation by activating Forkhead Box M1 and remission after Natura-α pretreatment.

Dibutyl phthalate (DBP) is widely used in perfumes, cosmetics, shampoos and medical devices. It is ubiquitous in the environment and greatly endangers people's health. Several studies have reported that being exposed to it can promote the development of lung cancer, breast cancer, hepatoma, and multiple myeloma. However, there are still few studies on the specific molecular mechanism and prevention methods of DBP promoting the progression of prostate cancer. This study, in silico, in vitro and in vivo, aims to explore the promoting effect of DBP on prostate cancer cell proliferation. In silico analysis, we obtained a set of DBP interactive genes by utilizing TCGA, CTD and GEO database. These genes are mainly enriched in cell cycle regulatory pathways and they have high degree of homogeneity. We found that these genes shared one transcription factor - Forkhead Box M1 (FOXM1) by performing Chip-X Enrichment Analysis (Version 3.0). FOXM1, once called the 2010 Molecule of the Year, aberrantly expressed in up to 20 kinds of tumors. In vitro experiments, we used DBP at concentrations of 10-8 M and 5 * 10-7 M to treat C4-2 and PC3 cells for 6 days, respectively. Cell viability was promoted significantly. When Natura-α was added in the background of above-mentioned concentration of DBP, this effect was significantly inhibited. In addition, we also found that DBP can interfering with the efficacy of enzalutamide therapy. The introduction of Natura-α can also reverse this phenomenon. In vivo, subcutaneous tumor formation experiments in nude mice, 800 mg/kg/day DBP can promote the growth of prostate cancer. This phenomenon was suppressed when Natura-α (100 mg/kg/day) was added. Based on the results of the above three levels, we confirmed that DBP can target FOXM1 to promote prostate cancer cell proliferation. Natura-α can reverse its cancer-promoting effect. This study provides new insights into the impact of DBP on prostate cancer.

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.

Superelastic and multifunctional fibroin aerogels from multiscale silk micro-nanofibrils exfoliated via deep eutectic solvent.

Superelastic silk fibroin (SF)-based aerogels can be used as multifunctional substrates, exhibiting a promising prospect in air filtration, thermal insulation, and biomedical materials. However, fabrication of the superelastic pure SF aerogels without adding synthetic polymers remains challenging. Here, the SF micro-nano fibrils (SMNFs) that preserved mesostructures are extracted from SF fibers as building blocks of aerogels by a controllable deep eutectic solvent liquid exfoliation technique. SMNFs can assemble into multiscale fibril networks during the freeze-inducing process, resulting in all-natural SMNF aerogels (SMNFAs) with hierarchical cellular architectures after lyophilization. Benefiting from these structural features, the SMNFAs demonstrate desirable properties including ultra-low density (as low as 4.71 mg/cm3) and superelasticity (over 85 % stress retention after 100 compression cycles at 60 % strain). Furthermore, the potential applications of superelastic SMNFAs in air purification and thermal insulation are investigated to exhibit their functionality, mechanical elasticity, and structural stability. This work provides a reliable approach for the fabrication of highly elastic SF aerogels and endows application prospects in air purification and thermal insulation opportunities.

CoP2/Co2P Encapsulated in Carbon Nanotube Arrays to Construct Self-Supported Electrodes for Overall Electrochemical Water Splitting.

Electrocatalytic water splitting is a desirable and sustainable strategy for hydrogen production yet still faces challenges due to the sluggish kinetics and rapid deactivation of catalysts in the oxygen evolution process. Herein, we utilized the metal-catalyzed growth technology and phosphating process to fabricate self-supported electrodes (CoxPy@CNT-CC) composed of carbon nanotube (CNT) arrays grown on carbon cloth (CC); thereinto, cobalt-based phosphide nanoparticles (CoxPy) are uniformly encapsulated in the cavity of the CNTs. After further optimization, when the nanoparticles are in the composite phase (CoP2/Co2P), CoP2/Co2P@CNT-CC served as catalytic electrodes with the highest activity and stability for electrocatalytic water splitting in an alkaline medium (1.0 M KOH). The as-prepared CoP2/Co2P@CNT-CC integrates the advantages of the abundant active sites and confinement effect of CNTs, imparting promising electrocatalytic activities and stability in catalyzing both hydrogen evolution reaction and oxygen evolution reaction. Remarkably, electrocatalytic water splitting cells assembled using CoP2/Co2P@CNT-CC electrodes as the cathode and anode, respectively, require a cell voltage of 1.55 V at 10 mA cm-2, which is lower than that of the commercially noble Pt/C/CC and RuO2/CC catalyst couple (1.68 V). Besides, a CoP2/Co2P@CNT-CC||CoP2/Co2P@CNT-CC system shows outstanding durability for a period of 100 h at 10 mA cm-2. This work may provide new ideas for designing bifunctional electrocatalysts for applications in electrocatalytic water splitting.

N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. METHODS: We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. RESULTS: We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. CONCLUSION: This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator.

Coupling of nanocrystal hexagonal array and two-dimensional metastable substrate boosts H2-production.

Designing well-ordered nanocrystal arrays with subnanometre distances can provide promising materials for future nanoscale applications. However, the fabrication of aligned arrays with controllable accuracy in the subnanometre range with conventional lithography, template or self-assembly strategies faces many challenges. Here, we report a two-dimensional layered metastable oxide, trigonal phase rhodium oxide (space group, P-3m1 (164)), which provides a platform from which to construct well-ordered face-centred cubic rhodium nanocrystal arrays in a hexagonal pattern with an intersurface distance of only 0.5 nm. The coupling of the well-ordered rhodium array and metastable substrate in this catalyst triggers and improves hydrogen spillover, enhancing the acidic hydrogen evolution for H2 production, which is essential for various clean energy-related devices. The catalyst achieves a low overpotential of only 9.8 mV at a current density of -10 mA cm-2, a low Tafel slope of 24.0 mV dec-1, and high stability under a high potential (vs. RHE) of -0.4 V (current density of ~750 mA cm-2). This work highlights the important role of metastable materials in the design of advanced materials to achieve high-performance catalysis.

Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment.

BACKGROUND: Tumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer. METHODS: In this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings. RESULTS: A total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that KRT6B was involved not only in epithelial-mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis. CONCLUSION: KRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial-mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.

Caspofungin at sub-inhibitory concentration promotes the formation of Candida albicans persister cells.

AIMS: Low caspofungin exposure is frequently encountered in patients with invasive candidiasis caused by Candida albicans. This study aimed to investigate the effects of caspofungin on C. albicans at sub-inhibitory concentrations. METHODS AND RESULTS: First, a comparative transcriptomics analysis was performed on C. albicans receiving caspofungin at sub-minimum inhibitory concentrations (sub-MICs). The results showed that caspofungin significantly changed the mRNA expression profile in DAY185, with DE-mRNAs enriched in the functions of cell wall biosynthesis, metabolism, etc. Subsequently, cellular fitness, cell aggregation, energy metabolism activity and the proportion of persister cells of C. albicans were quantitatively and/or qualitatively assessed after sub-MIC caspofungin exposure. No significant changes in cell fitness and aggregation formation were observed during treatment of C. albicans with sub-MIC caspofungin. In C. albicans aggregation treated with sub-MIC caspofungin, we observed a decrease in respiratory metabolism and an increase in persister cells; this effect was more pronounced in als1ΔΔ than in DAY185. CONCLUSIONS: Pre-exposure to sub-MIC caspofungin suppresses C. albicans respiratory metabolism and promotes persister cell development. SIGNIFICANCE AND IMPACT OF THE STUDY: Caspofungin should be used with caution in patients with C. albicans infections, as anti-infection therapy may fail due to persister cells.

Exosomes in urological diseases - Biological functions and clinical applications.

Exosomes are extracellular vesicles with a variety of biological functions that exist in various biological body fluids and exert their functions through proteins, nucleic acids, lipids, and metabolites. Recent discoveries have revealed the functional and biomarker roles of miRNAs in urological diseases, including benign diseases and malignancies. Exosomes have several uses in the diagnosis, treatment, and monitoring of urological diseases, especially cancer. Proteins and nucleic acids can be used as alternative biomarkers for detecting urological diseases. Additionally, exosomes can be detected in most body fluids, thereby avoiding pathogenesis. More importantly, for urological tumors, exosomes display a higher sensitivity than circulating tumor cells and tumor-derived DNA in body fluid biopsies because of their low immunogenicity and high stability. These advantages have made it a research hotspot in recent years. In this review, we focus on the biological characteristics and functions of exosomes and summarize their advantages and the latest progress in the diagnosis and treatment of urological diseases.

Metabolic Profiling of Bladder Cancer Patients' Serum Reveals Their Sensitivity to Neoadjuvant Chemotherapy.

Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively before the first chemotherapy for untargeted metabolomics by 1H-NMR and UPLC-MS. To identify characterized metabolites, multivariate statistical analyses were applied, and the intersection of the differential metabolites discovered by the two approaches was used to identify viable biomarkers. A total of 18 patients (6 NAC-sensitive patients and 12 NAC-resistant patients) were enrolled. There were 29 metabolites detected by 1H-NMR and 147 metabolites identified by UPLC-MS. Multivariate statistics demonstrated that in the sensitive group, glutamine and taurine were considerably increased compared to their levels in the resistant group, while glutamate and hypoxanthine were remarkably decreased. Pathway analysis and enrichment analysis showed significant alterations in amino acid pathways, suggesting that response to chemotherapy may be related to amino acid metabolism. In addition, hallmark analysis showed that DNA repair played a regulatory role. Overall, serum metabolic profiles of NAC sensitivity are significantly different in bladder cancer patients. Glycine, hypoxanthine, taurine and glutamine may be the potential biomarkers for clinical treatment. Amino acid metabolism has potential value in enhancing drug efficacy.