Deciphering the prognostic features of bladder cancer through gemcitabine resistance and immune-related gene analysis and identifying potential small molecular drug PIK-75.

BACKGROUND: Bladder cancer (BCa) stands out as a prevalent and highly lethal malignancy worldwide. Chemoresistance significantly contributes to cancer recurrence and progression. Traditional Tumor Node Metastasis (TNM) stage and molecular subtypes often fail to promptly identify treatment preferences based on sensitivity. METHODS: In this study, we developed a prognostic signature for BCa with uni-Cox + LASSO + multi-Cox survival analysis in multiple independent cohorts. Six machine learning algorithms were adopted to screen out the hub gene, RAC3. IHC staining was used to validate the expression of RAC3 in BCa tumor tissue. RT-qPCR and Western blot were performed to detect and quantify the mRNA and protein levels of RAC3. CCK8, colony formation, wound healing, and flow cytometry analysis of apoptosis were employed to determine cell proliferation, migration, and apoptosis. Molecular docking was used to find small target drugs, PIK-75. 3D cell viability assay was applied to evaluate the ATP viability of bladder cancer organoids before and after PIK-75 treated. RESULTS: The established clinical prognostic model, GIRS, comprises 13 genes associated with gemcitabine resistance and immunology. This model has demonstrated robust predictive capabilities for survival outcomes across various independent public cohorts. Additionally, the GIRS signature shows significant correlations with responses to both immunotherapy and chemotherapy. Leveraging machine learning algorithms, the hub gene, RAC3, was identified, and potential upstream transcription factors were screened through database analysis. IHC results showed that RAC3 was higher expressed in GEM-resistant BCa patients. Employing molecular docking, the small molecule drug PIK-75, as binding to RAC3, was identified. Experiments on cell lines, organoids and animals validated the biological effects of PIK-75 in bladder cancer. CONCLUSIONS: The GIRS signature offers a valuable complement to the conventional anatomic TNM staging system and molecular subtype stratification in bladder cancer. The hub gene, RAC3, plays a crucial role in BCa and is significantly associated with resistance to gemcitabine. The small molecular drug, PIK-75 having the potential as a therapeutic agent in the context of gemcitabine-resistant and immune-related pathways.

Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment.

Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.

Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity.

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.

FGFR3 mutation characterization identifies prognostic and immune-related gene signatures in bladder cancer.

BACKGROUND: Immunotherapy and FGFR3-targeted therapy play an important role in the management of locally advanced and metastatic bladder cancer (BLCA). Previous studies indicated that FGFR3 mutation (mFGFR3) may be involved in the alterations of immune infiltration, which may affect the priority or combination of these two treatment regimes. However, the specific impact of mFGFR3 on the immunity and how FGFR3 regulates the immune response in BLCA to affect prognosis remain unclear. In this study, we aimed to elucidate the immune landscape associated with mFGFR3 status in BLCA, screen immune-related gene signatures with prognostic value, and construct and validate a prognostic model. METHODS: ESTIMATE and TIMER were used to assess the immune infiltration within tumors in the TCGA BLCA cohort based on transcriptome data. Further, the mFGFR3 status and mRNA expression profiles were analyzed to identify immune-related genes that were differentially expressed between patients with BLCA with wild-type FGFR3 or mFGFR3 in the TCGA training cohort. An FGFR3-related immune prognostic score (FIPS) model was established in the TCGA training cohort. Furthermore, we validated the prognostic value of FIPS with microarray data in the GEO database and tissue microarray from our center. Multiple fluorescence immunohistochemical analysis was performed to confirm the relationship between FIPS and immune infiltration. RESULTS: mFGFR3 resulted in differential immunity in BLCA. In total, 359 immune-related biological processes were enriched in the wild-type FGFR3 group, whereas none were enriched in the mFGFR3 group. FIPS could effectively distinguish high-risk patients with poor prognosis from low-risk patients. The high-risk group was characterized by a higher abundance of neutrophils; macrophages; and follicular helper, CD4, and CD8 T-cells than the low-risk group. In addition, the high-risk group exhibited higher expression of PD-L1, PD-1, CTLA-4, LAG-3, and TIM-3 than the low-risk group, indicating an immune-infiltrated but functionally suppressed immune microenvironment. Furthermore, patients in the high-risk group exhibited a lower mutation rate of FGFR3 than those in the low-risk group. CONCLUSIONS: FIPS effectively predicted survival in BLCA. Patients with different FIPS exhibited diverse immune infiltration and mFGFR3 status. FIPS might be a promising tool for selecting targeted therapy and immunotherapy for patients with BLCA.

Immune Co-inhibitory Receptors CTLA-4, PD-1, TIGIT, LAG-3, and TIM-3 in Upper Tract Urothelial Carcinomas: A Large Cohort Study.

Programmed cell death 1 ligand 1), programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3, lymphocyte activation gene-3, and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in upper tract urothelial carcinoma (UTUC). The aim of this Cohort Study was to provide evidence concerning expression profiles and the clinical significance of CIRs among Chinese UTUC patients. A total of 175 UTUC patients who received radical surgery in our center were included. We used immunohistochemistry to evaluate CIR expressions in tissue microarrays (TMAs). Clinicopathological characteristics and prognostic correlations of CIR proteins were retrospectively analyzed. TIGIT, T-cell immunoglobulin and mucin-domain containing-3, PD-1, CTLA-4, Programmed cell death 1 ligand 1, and lymphocyte activation gene-3 high expression was examined in 136(77.7%), 86(49.1%), 57(32.6%), 18(10.3%), 28(16.0%), and 18(10.3%) patients, respectively. Log-rank tests and Multivariate Cox analysis both implied CTLA-4 and TIGIT expression was associated with worse relapse-free survival. In conclusion, this is the largest Chinese UTUC cohort study, and we analyzed the Co-inhibitory receptor expression profiles in UTUC. We identified CTLA-4 and TIGIT expression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced UTUCs are probably immunogenic, for which single or combined immunotherapy may be potential therapeutic approaches in the future.

Study on phase evolution and promoting the pozzolanic activity of electrolytic manganese residue during calcination.

Electrolytic manganese residue (EMR) is a harmful by-product in the electrolytic manganese industry. Calcination is an efficient method for disposing EMR. In this study, thermogravimetric-mass spectrometry (TG-MS) combined with X-ray diffraction (XRD) was used for analysing the thermal reactions and phase transitions during calcination. The pozzolanic activity of calcined EMR was determined by the potential hydraulicity test and strength activity index (SAI) test. The leaching characteristics of Mn were determined by TCLP test and BCR SE method. The results showed that MnSO4 was converted into stable MnO2 during calcination. Meanwhile, Mn-rich bustamite (Ca0.228Mn0.772SiO3) was converted into Ca(Mn, Ca)Si2O6. The gypsum was transformed into anhydrite and then decomposed into CaO and SO2. Additionally, the organic pollutants and ammonia were completely removed following calcination at 700 °C. The leaching concentration of Mn decreased from 819.9 mg L-1 to 339.6 mg L-1 following calcination at 1100 °C. The chemical forms of Mn were transformed from acid-soluble fraction to residual fraction. The pozzolanic activity tests indicated that EMR1100-Gy maintained a complete shape. The compressive strength of EMR1100-PO reached 33.83 MPa. Finally, the leaching concentrations of heavy metals met the standard limits. This study provides a better understanding for the treatment and utilization of EMR.

Inherited mutations in Chinese patients with upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) accounts for 10% of urothelial carcinomas (UCs) and has a substantial hereditary component. However, the majority of our knowledge of germline spectrum comes from bladder cancer (BCa) data in White populations. Here, we sequence 309 Chinese UTUC cases and identify 71 germline pathogenic/likely pathogenic (P/LP) mutations in 62 patients (20.1%). Compared with White cases, we observe disparities and similarities in inherited mutational profiles. Association analysis reveals that germline P/LP mutations in MSH2, BRCA2, BRCA1, and BRIP1 significantly increase UTUC risk in Chinese populations. Furthermore, germline P/LP mutation in homologous recombination genes indicates poor prognosis for non-metastatic UTUC. Finally, we perform paired sequencing and observe significant correlations between germline mutation patterns and tumor subtypes. This study highlights the importance of genetic testing in patients with UTUC and calls for germline data from various ethnicities to better understand this disease.

Prevalence of mismatch repair genes mutations and clinical activity of PD-1 therapy in Chinese prostate cancer patients.

Prostate cancer (PCa) patients with mismatch repair (MMR) genes mutations are potentially responsive to immune checkpoint blockade (ICB). However, aberrations in MMR genes were rare in PCa and there is evidence that MMR genes mutations are highly ethnic specific. Thus, the prevalence and clinical characteristics of this subgroup in Chinese PCa patients are largely unknown. Furthermore, why some of these patients do not respond to ICB also remains unclear. Here, we analyzed the sequencing data from 3338 Chinese PCa patients to profile the mutation spectrum of the MMR genes. We found that in metastatic disease, the pathogenic mutation frequency of MMR genes in Chinese PCa patients was higher than that in the Caucasus population (4.8 vs 2.2%, P = 0.006) and the mutation carriers responded poorer to androgen deprive therapy (ADT) and abiraterone than non-carriers. Besides, we reported a multi-institutional cases series of 11 PCa patients with mismatch repair deficiency (dMMR) or microsatellite instability high (MSI-H) who received programmed cell death receptor-1 (PD-1) inhibitors, and performed multiplex immunohistochemistry (mIF) to explore the relationship between tumor immune microenvironment (TIME) and response to ICB. The results showed that the responders had higher density of intratumoral CD8+ T cells than non-responders. Our data suggested MMR genes mutations may be more common in Chinese PCa patients, and it is associated with poorer response to hormonal therapies. We propose that the density of intratumoral CD8+ T cells could be a promising predictor to help further subdivide the population of PCa patients who can benefit from immunotherapy.

Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas.

Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients' clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.

Application of Internet-based multidisciplinary management in patients with genitourinary cancers in China: A brief introduction to a new model of healthcare service for cancer survivors during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has triggered multiple global healthcare system crises. Apart from the pandemic itself, the travel restriction and social distance policy for the purpose of epidemic control has cast a shadow on the management of cancer survivors. Cancer survivors suffered a double blow from both the epidemic and cancer. To deal with the challenge, we explored a new Internet-based patient management model. This model has overcome the limitation of time and space and thus can help oncologists to provide remote multidisciplinary healthcare services for cancer survivors. These patients can get high-quality cancer management from multidisciplinary experts without too much transportation. This model has been applied in patients with genitourinary cancers and proved to be effective and efficient. Our study demonstrated that more patients benefited from this model during the pandemic of COVID-19, especially in those affected heavily by COVID-19. These results suggested that it can also give insight into the management of other cancer survivors in China. Given the long-term impact of the COVID-19 pandemic, we would like to introduce our new model of healthcare service and the application of Internet-based multidisciplinary management to our global peers and medical industries to help their cancer survivors who are delayed in treatment due to the COVID-19 pandemic.

Deciphering the active origin for urea oxidation reaction over nitrogen penetrated nickel nanoparticles embedded in carbon nanotubes.

Urea electrooxidation with favorable thermodynamic potential is highly anticipated but suffering from sluggish kinetics. Deciphering the activity origin and achieving rational structure design are pivotal for developing highly efficient electrocatalyst for urea oxidation reaction (UOR). Herein, nitrogen penetrated nickel nanoparticles confined in carbon nanotubes (Ni-NCNT) is successfully achieved to drive UOR. Active origin of Ni-NCNT is decoded to be the in-situ generated Ni2+δO(OH)ads according to comprehensive analysis. The electrophilic Ni2+δ and protophilic OHads could targeted capture O and H atoms from urea, respectively, achieving molecule activation and accelerating the subsequent proton coupled electron transfer reactions. Nitrogen penetration is identified to promote prior formation of Ni2+δO(OH)ads and push up the d band center of Ni-NCNT, enhancing urea adsorption and subsequent molecule cleavage reactions. As a result, Ni-NCNT exhibits superior UOR performance. This work supplies valuable insights for the rational design and construction of efficient nickel-based catalyst for driving UOR.

Potentiality of phosphorus-accumulating organisms biomasses in biosorption of Cd(II), Pb(II), Cu(II) and Zn(II) from aqueous solutions: Behaviors and mechanisms.

Heavy metal pollution is consistently a critical global issue, and bioremediation is regarded as one of the most promising approaches. In this work, the biosorption characteristics of Cd(II), Pb(II), Cu(II) and Zn(II) from aqueous solutions using three phosphorus-accumulating organisms (PAOs) biomasses, Ochrobactrum cicero (PAB-006), Stenotrophomonas maltophilia (PAB-009), and Pseudomonas putida (PAB-0031), as biosorbents were investigated. Results indicated that the equilibrium biosorption capacities of biosorbents to heavy metal ions were sensitive to the solution pH, and increased with increasing pH values. The experimental data of Cd(II), Pb(II), Cu(II) and Zn(II) biosorption were in good agreement with the Pseudo-second-order, Redlich-Peterson and Temkin models, implying that the biosorption was a hybrid chemical reaction-biosorption process. In addition, the theoretical maximum biosorption capacities of Cd(II), Pb(II), Cu(II) and Zn(II) were calculated to be 67.84, 80.23, 50.56 and 63.07 mg/g for PAB-006, 59.99, 87.71, 39.26 and 64.00 mg/g for PAB-009 and 68.31, 85.43, 38.97 and 62.85 mg/g for PAB-031, respectively (pH = 5.0 ± 0.1, T = 25 °C), according to the parameters of the Langmuir model. Moreover, ionic strength had negligible influences or slight promoting effects, while humic acid exhibited positive effects on the removal of heavy metals. Further, PABs were stable and displayed excellent reusability. Characterization techniques of FTIR and XPS revealed that surface complexation, ion exchange, hydrogen bonding and electrostatic interaction were the main mechanisms involved in the biosorption process. In summary, the biosorbent PABs possessed high biosorption performance with excellent reusability, and which hold the great application prospect in the treatment of heavy metal contaminated water.

Removal of heavy metal(loid)s from aqueous solution by biogenic FeS-kaolin composite: Behaviors and mechanisms.

In this work, a green adsorbent, biogenic FeS-kaolin composite (KL-FeS) was synthesized by sulfate-reducing bacteria (SRB) mediation, and its potential for Cd(II), Pb(II), Cu(II), Zn(II), As(III) and Sb(III) removal was evaluated. Among prepared composites, the KL-FeS synthesized at a concentration of 2 g/L kaolin performed a better removal efficiency on heavy metal(loid)s and the adsorption results followed the pseudo-second-order and Redlich-Peterson models, indicating that the adsorption was a hybrid chemical reaction-adsorption process. Additionally, the maximum adsorption capacities of Cd(II), Pb(II), Cu(II), Zn(II), As(III) and Sb(III) on KL-FeS in monocomponent system were 71.71, 133.54, 51.90, 54.41, 38.71 and 96.38 mg/g, respectively (pH = 5.0 ± 0.1, T = 25 °C). In addition, the increase of pH and ionic strength promoted the adsorption capacities of KL-FeS for metal-(loid)s. Moreover, FTIR, XPS and XRD analyses supported that surface complexation, hydrogen bonding, ion exchange, electrostatic interaction and chemical precipitation were predominately mechanisms involved in the adsorption process. Furthermore, KL-FeS displayed higher affinity for Pb(II), Sb(III) and Cu(II) in the multi-component system. This work highlighted the potential of biogenic FeS-kaolin composite for simultaneous removal of multiple heavy metal(loid)s under aerobic conditions.

Stromal Tumor-Associated Macrophage Infiltration Predicts Poor Clinical Outcomes in Muscle-Invasive Bladder Cancer Patients.

BACKGROUND: This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value. RESULTS: Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006-1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition. CONCLUSIONS: Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.

IL-1A is associated with postoperative survival and immune contexture in clear cell renal cell carcinoma.

BACKGROUND: Interleukin-1α (IL-1α) is thought to play a major role in renal cell carcinoma (RCC), but the specific mechanism is unclear. In this study, we explored the potential mechanism of the role of IL-1α in RCC. METHODS: Two cohorts were included in this study: The Cancer Genome Atlas (TCGA) cohort (n=521) and Fudan University Shanghai Cancer Center (FUSCC) cohort (n=198). These cohorts were used for cell infiltration-related analyses. RESULTS: In TCGA cohort, expression of IL-1α was significantly increased in patients with RCC. High IL-1α mRNA expression and intratumoral IL-1α+ cells were correlated with poor OS, which remained significant after adjustment for confounders. Elevated IL-1α mRNA expression and increased intratumoral IL-1α+ cell infiltration were associated with less mast cell infiltration in RCC. Among the relationships between IL-1α and cytotoxic factors, IL-1α was correlated with IFN-γ, TNFSF11, and GZMA. Among the relationships between IL-1α and immunosuppressive factors, we found that IL-1α was correlated with PDCD1, CD274, CTL1A4, LAG3, and BTLA. CONCLUSION: Expression of IL-1α was significantly correlated with the prognosis of RCC patients. IL-1α may participate in the development and progression of renal cancer through interactions with immune infiltrating mast cells. Our data demonstrate that IL-1α is a prognostic factor and potential therapeutic target for RCC.

Exosome-derived circTRPS1 promotes malignant phenotype and CD8+ T cell exhaustion in bladder cancer microenvironments.

Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.

Interfacial Covalent Bonding Endowing Ti3 C2 -Sb2 S3 Composites High Sodium Storage Performance.

Antimony sulfide is attracting enormous attention due to its remarkable theoretical capacity as anode for sodium-ion batteries (SIBs). However, it still suffers from poor structural stability and sluggish reaction kinetics. Constructing covalent chemical linkage to anchor antimony sulfide on two-dimension conductive materials is an effective strategy to conquer the challenges. Herein, Ti3 C2 -Sb2 S3 composites are successfully achieved with monodispersed Sb2S3 uniformly pinned on the surface of Ti3 C2 Tx MXene through covalent bonding of Ti-O-Sb and S-Ti. Ti3 C2 Tx MXene serves as both charge storage contributor and flexible conductive buffer to sustain the structural integrity of the electrode. Systematic analysis indicates that construction of efficient interfacial chemical linkage could bridge the physical gap between Sb2S3 nanoparticles and Ti3 C2 Tx MXene, thus promoting the interfacial charge transfer efficiency. Furthermore, the interfacial covalent bonding could also effectively confine Sb2S3 nanoparticles and the corresponding reduced products on the surface of Ti3 C2 Tx MXene. Benefited from the unique structure, Ti3 C2 -Sb2 S3 anode delivers a high reversible capacity of 475 mAh g-1 at 0.2 A g-1 after 300 cycles, even retaining 410 mAh g-1 at 1.0 A g-1 after 500 cycles. This strategy is expected to shed more light on interfacial chemical linkage towards rational design of advanced materials for SIBs.

Long noncoding RNA LINC00641 promotes renal cell carcinoma progression via sponging microRNA-340-5p.

BACKGROUND: Emerging evidences have revealed that long non-coding RNAs (lncRNAs) have played critical roles in tumor occurrence and progression. LINC00641 has been reported to be involved in the initiation and development of several cancers in the recent years. However, the detailed biological role of LINC00641 in renal cell carcinoma (RCC) remains largely unclear. METHODS: In this study, the expression and biological function of LINC00641 were assessed in renal carcinoma both in vitro and in vivo. Cell proliferation, migration and colony formation assay were performed to explore the effect of LINC00641on growth, progression and invasion of RCC cell. qRT-PCR, flow cytometry and luciferase reporter assay and in vivo tumorigenicity assay were also carried out. RESULTS: The expression of LINC00641 was overexpressed in RCC tissues and cell lines, and high LINC00641 expression was correlated with tumor-node-metastasis stage. Furthermore, Silencing of LINC00641 remarkably inhibited the ability of cell proliferation, colony formation, and invasive capacities, as well as increasing the apoptotic rates of RCC cells in vitro. Mechanistically, miR-340-5p was validated to be targeted by LINC00641 and knockdown of miR-340-5p counteracted LINC00641 silencing-mediated inhibition of RCC progression. In addition, in vivo experiment confirmed the findings discovered in vitro. CONCLUSIONS: These results suggested that LINC00641 promoted the progression of RCC by sponging miR-340-5p.

Nitrogen doped porous carbon coated antimony as high performance anode material for sodium-ion batteries.

Sb holds the promise of being a high performance anode for sodium ion batteries(SIBs), while effective preparation of decent antimony(Sb) based anode materials for sodium storage is still under exploration. Herein, we propose a simple approach to achieve a high performance anode, using polyaniline as the carbon source and SbCl3as the metal source. Synergetic polymerization and hydrolysis reactions combined with subsequent thermal reduction endow Sb/C-PANI electrode possessing ultrafine Sb nanoparticles symmetrically distributed in the nitrogen(N) doped porous carbon matrix. The Sb/C-PANI electrode exhibits excellent sodium storage performance, featured for a high reversible capacity of 469.5 mAh g-1after 100 cycles at 100 mA g-1and 336.5 mAh g-1after 300 cycles under 500 mA g-1. Such impressive performance will advance the development of Sb based anode materials for sodium storage. The present approach provides a compatible strategy for preparation of anode materials with high reversible capacity and long lifespan.