Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway.

BACKGROUND: Docetaxel resistance represents a significant obstacle in the treatment of prostate cancer. The intricate interplay between cytokine signalling pathways and transcriptional control mechanisms in cancer cells contributes to chemotherapeutic resistance, yet the underlying molecular determinants remain only partially understood. This study elucidated a novel resistance mechanism mediated by the autocrine interaction of interleukin-11 (IL-11) and its receptor interleukin-11 receptor subunit alpha(IL-11RA), culminating in activation of the JAK1/STAT4 signalling axis and subsequent transcriptional upregulation of the oncogene c-MYC. METHODS: Single-cell secretion profiling of prostate cancer organoid was analyzed to determine cytokine production profiles associated with docetaxel resistance.Analysis of the expression pattern of downstream receptor IL-11RA and enrichment of signal pathway to clarify the potential autocrine mechanism of IL-11.Next, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) was performed to detect the nuclear localization and DNA-binding patterns of phosphorylated STAT4 (pSTAT4). Coimmunoprecipitation and reporter assays were utilized to assess interaction between pSTAT4 and the cotranscription factor CREB-binding protein (CBP) as well as their role in c-MYC transcriptional activity. RESULTS: Autocrine secretion of IL-11 was markedly increased in docetaxel-resistant prostate cancer cells. IL-11 stimulation resulted in robust activation of JAK1/STAT4 signalling. Upon activation, pSTAT4 translocated to the nucleus and associated with CBP at the c-MYC promoter region, amplifying its transcriptional activity. Inhibition of the IL-11/IL-11RA interaction or disruption of the JAK1/STAT4 pathway significantly reduced pSTAT4 nuclear entry and its binding to CBP, leading to downregulation of c-MYC expression and restoration of docetaxel sensitivity. CONCLUSION: Our findings identify an autocrine loop of IL-11/IL-11RA that confers docetaxel resistance through the JAK1/STAT4 pathway. The pSTAT4-CBP interaction serves as a critical enhancer of c-MYC transcriptional activity in prostate cancer cells. Targeting this signalling axis presents a potential therapeutic strategy to overcome docetaxel resistance in advanced prostate cancer.

MT1G, an emerging ferroptosis-related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer.

BACKGROUND: Prostate cancer is a leading cause of cancer-related deaths in men worldwide. Despite advances in treatment strategies, there is still a need for novel therapeutic targets and approaches. Ferroptosis has emerged as a critical process in the development and progression of several cancers, including prostate cancer (PCA). In this study, we investigate the role of MT1G, a gene implicated in immune responses and ferroptosis, in the pathogenesis of PCA. Our objective is to elucidate its prognostic significance and its impact on the tumor microenvironment, while exploring its potential in enhancing the sensitivity to immune checkpoint inhibitor (ICI) therapy. METHODS: We utilized a combination of in silico analysis and experimental techniques to investigate the role of MT1G in PCA. First, we analyzed large-scale genomic datasets to assess the expression pattern and prognostic significance of MT1G in PCA patients. Subsequently, we performed functional assays to explore the impact of MT1G in PCA and its potential involvement in modulating immune responses. In addition, we conducted in vivo experiments to evaluate the effect of MT1G on tumor growth and response to ICI therapy. RESULTS: Our analysis revealed that MT1G expression is significantly downregulated in PCA tissues compared to normal prostate tissues and is associated with poor prognosis. Furthermore, MT1G overexpression inhibited the growth of PCA cells in vitro and in vivo. Importantly, we found that MT1G regulates the tumor microenvironment by modulating immune cell infiltration and inhibiting immunosuppressive factors. Furthermore, our study reveals a significant correlation between MT1G expression levels and the response to immune checkpoint inhibitor (ICI) therapy in prostate cancer (PCA) patients, as MT1G upregulation leads to an increase in PDL-1 expression. These findings underscore the potential of MT1G as a promising predictive biomarker for ICI therapy response in PCA patients. CONCLUSION: Our study elucidates the pivotal role played by MT1G in the pathogenesis of prostate cancer (PCA) and its profound implications for prognosis. Moreover, it raises the intriguing possibility that MT1G could pave the way for novel therapeutic approaches in PCA treatment. This potential arises from its ability to orchestrate immune infiltration within the tumor microenvironment, consequently enhancing sensitivity to immune checkpoint inhibitor (ICI) therapy. Therefore, our findings hold substantial promise for advancing our comprehension of PCA and exploring innovative therapeutic strategies.

The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment.

BACKGROUND: Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge. METHODS: We explored the role of Ribonucleotide reductase subunit M2 (RRM2), a gene associated with senescence, in the sensitivity of prostate cancer to docetaxel. We evaluated the RRM2 expression, docetaxel resistance, and ANXA1 expression in prostate cancer cell lines and tumour xenografts models. In addition, We assessed the impact of RRM2 knockdown, ANXA1 over-expression, and PI3K/AKT pathway inhibition on the sensitivity of prostate cancer cells to docetaxel. Furthermore, we assessed the sensitivity of prostate cancer cells to the combination treatment of COH29 and docetaxel. RESULTS: Our results demonstrated a positive association between RRM2 expression and docetaxel resistance in prostate cancer cell lines and tumor xenograft models. Knockdown of RRM2 increased the sensitivity of prostate cancer cells to docetaxel, suggesting its role in mediating resistance. Furthermore, we observed that RRM2 stabilizes the expression of ANXA1, which in turn activates the PI3K/AKT pathway and contributes to docetaxel resistance. Importantly, we found that the combination treatment of COH29 and docetaxel resulted in a synergistic effect, further augmenting the sensitivity of prostate cancer cells to docetaxel. CONCLUSION: Our findings suggest that RRM2 regulates docetaxel resistance in prostate cancer by stabilizing ANXA1-mediated activation of the PI3K/AKT pathway. Targeting RRM2 or ANXA1 may offer a promising therapeutic strategy to overcome docetaxel resistance in prostate cancer.

POSS-based polyionic liquids for efficient CO2 cycloaddition reactions under solvent- and cocatalyst-free conditions at ambient pressure.

The conversion of CO2 into value-added chemicals has become an imminent research topic and the cycloaddition of CO2 with a C1 resource to produce cyclic carbonates is a promising pathway for CO2 utilization. Herein, a series of POSS-based polyionic liquids (PILs) were synthesized by the copolymerization of octavinyl polyhedral oligomeric silsesquioxane (POSS) with an imidazolium ion linker. The prepared PILs have the characteristics of hydrogen bond donors, halogen atom sites, stable pore structures, and thermal stability, and are used as heterogeneous catalysts for the cycloaddition of epoxides with carbon dioxide. The effect of linkers on the cycloaddition is investigated by tuning the ratio of POSS units to imidazolium ions. Under the optimized conditions, the conversion of epichlorohydrin can reach 99.18% at atmospheric pressure with neither co-catalysts nor solvents. It is concluded that the reaction of the cycloaddition of epoxides with carbon dioxide follows pseudo-first-order kinetics. Moreover, the presence of the catalysis of PILs leads to a significant decrease in the activation energy barrier for cycloaddition. The catalyst can be facilely recovered due to its high stability, and only a slight decrease in conversion was observed after five successive runs. In addition, the mechanism of PILs catalyzing the cycloaddition reaction of epoxides with CO2 is proposed. This work not only provides a sustainable and green process for CO2 cycloaddition, but also highlights the potential of using PILs for CO2 utilization.

Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis.

BACKGROUND: The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In the current study, the authors aim to compare the long-term oncological outcomes of POPRC versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort. PATIENTS AND METHODS: Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival and recurrence-free survival. To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching was performed. RESULTS: Among the 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After propensity score matching, each cohort included 99 matched patients. The OS ( P =0.940), cancer-specific survival ( P =0.957), and recurrence-free survival ( P =0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (Hazard ratio 0.874, 95% CI 0.592-1.290; P =0.498). CONCLUSIONS: The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.

SYTL2 promotes metastasis of prostate cancer cells by enhancing FSCN1-mediated pseudopodia formation and invasion.

BACKGROUND: Metastatic prostate cancer (mPCa) has a poor prognosis with limited treatment options. The high mobility of tumor cells is the key driving characteristic of metastasis. However, the mechanism is complex and far from clarified in PCa. Therefore, it is essential to explore the mechanism of metastasis and discover an intrinsic biomarker for mPCa. METHODS: Transcriptome sequencing data and clinicopathologic features of PCa from multifarious public databases were used to identify novel metastatic genes in PCa. The PCa tissue cohort containing 102 formalin-fixed paraffin-embedded (FFPE) samples was used to evaluate the clinicopathologic features of synaptotagmin-like 2 (SYTL2) in PCa. The function of SYTL2 was investigated by migration and invasion assays and a 3D migration model in vitro and a popliteal lymph node metastasis model in vivo. We performed coimmunoprecipitation and protein stability assays to clarify the mechanism of SYTL2. RESULTS: We discovered a pseudopodia regulator, SYTL2, which correlated with a higher Gleason score, worse prognosis and higher risk of metastasis. Functional experiments revealed that SYTL2 promoted migration, invasion and lymph node metastasis by increasing pseudopodia formation in vitro and in vivo. Furthermore, SYTL2 induced pseudopodia formation by enhancing the stability of fascin actin-bundling protein 1 (FSCN1) by binding and inhibiting the proteasome degradation pathway. Targeting FSCN1 enabled rescue and reversal of the oncogenic effect of SYTL2. CONCLUSIONS: Overall, our study established an FSCN1-dependent mechanism by which SYTL2 regulates the mobility of PCa cells. We also found that the SYTL2-FSCN1-pseudopodia axis may serve as a pharmacological and novel target for treating mPCa.

SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.

BACKGROUND: The mechanism involved in prostate cancer (PCa) metastasis is still poorly understood, and several oncogenes are known to regulate this process. However, the role of spalt-like transcription factor 4 (SALL4) in PCa metastasis remains unclear. METHODS: We performed RNA-sequencing to compare the mRNA expression profiles of seven localized PCa tissues and six metastatic PCa tissues. SALL4 was then identified and compared in the localized PCa and metastatic PCa. Immunohistochemical studies, qRT-PCR, and Western blot were performed to analyze the expression of SALL4 in PCa patients and cell lines. SALL4 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database and in our 68 clinical samples. Subsequently, we knocked down SALL4 in DU145 and PC3 cells and performed a series of functional assays to explore the effect of SALL4 on PCa progression. Finally, protein levels of SALL4 and core components of the MAPK pathway were measured by Western blot, and cells were treated with PD0325901 to observe proliferation and metastasis. RESULTS: Significantly higher expression of SALL4 was found in metastatic PCa than in localized PCa. In addition, high SALL4 expression was significantly associated with high pathological T stage, N stage, Gleason score, and poor disease-free survival in TCGA database and in our clinical samples. Functional studies indicated that knockdown of SALL4 in DU145 and PC3 inhibited proliferation, migration, and angiogenesis. Furthermore, the ERK and P38 protein phosphorylation significantly reduced after knockdown of SALL4 in DU145 and PC3, indicating the inactivation of the MAPK signaling pathway. Finally, the proliferation and migration ability of DU145 and PC3 cells were significantly decreased after PD0325901 treatment. CONCLUSIONS: SALL4 predicts unfavorable outcome and is closely associated with PCa progression, suggesting that SALL4 may be a promising prognostic marker and potential therapeutic target for PCa.

Substrate engineering of plasmonic nanocavity antenna modes.

Plasmonic nanocavities have emerged as a promising platform for next-generation spectroscopy, sensing and photonic quantum information processing technologies, benefiting from a unique confluence of nanoscale compactness and integrability, ultrafast functionality and room-temperature viability. Harnessing their unprecedented optical field confinement and enhancement properties for such diverse application domains, however, demands continued innovation in cavity design and robust strategies for engineering their plasmonic mode characteristics, with the aim of optimizing spatial and spectral matching conditions for strong light-matter interaction involving embedded quantum emitters. Adopting the canonical gold bowtie nanoantenna, we show that the complex refractive index, n + ik, of the substrate material provides additional design flexibility in tailoring the properties of plasmonic nanocavity modes, including their resonance wavelengths, hotspot locations, intracavity field polarization and radiative decay rates. In particular, we predict that highly refractive (n ≥ 4) or highly absorptive (k ≥ 4) substrates provide two complementary approaches to engineering nanocavity modes that are especially desirable for coupling two-dimensional quantum materials, featuring namely an elevated hotspot with a dominantly in-plane polarized near-field, as well as a strongly radiative character. Our study elucidates the benefits and intricacies of a largely unexplored facet of nanocavity mode manipulation, beyond the widely practiced synthetic control over the cavity topology or physical dimensions, and paves the way for plasmonic cavity quantum electrodynamics with two-dimensional excitonic matter.

Ionic Conjugated Polymers as Heterogeneous Catalysts for the Cycloaddition of Carbon Dioxide to Epoxides to Form Carbonates under Solvent- and Cocatalyst-Free Conditions.

The generation of cyclic carbonates by the cycloaddition of CO2 with epoxides is attractive in the industry, by which CO2 is efficiently used as C1 source. Herein, a series of catalysts were developed to efficient mediate the cycloaddition of CO2 with epoxides to generate carbonates. The catalysts were easily synthesized via the amine-formaldehyde condensation of ethidium bromide with a variety of linkers. The newly prepared heterogeneous catalysts have high thermal stability and degradation temperatures. The surface of the catalysts is smooth and spherical in shape. The effect of temperature, pressure, reaction time and catalyst dosage on the cycloaddition of CO2 with epoxide were investigated. The results show that the catalyst with 1,3,5-tris(4-formylphenyl)benzene as the linker can achieve 97.4 % conversion efficiency at the conditions of 100 °C, reaction time of 12 h, and the reaction pressure of 1.2 MPa in a solvent-free environment. Notably, the polymers serve as homogeneous catalysts during the reaction (reaction temperature above Tg ) and can be separated and recovered easily as homogeneous catalysts at room temperature. In addition, the catalyst is not only suitable for a wide range of epoxide substrates, but also can be recycled many times. Furthermore, DFT calculations show that the coordination between the electrophilic center of the catalyst and the epoxide reduces the energy barrier, and the reaction mechanism is proposed based on the reaction kinetic studies and DFT calculations.

Bibliometric analysis of the global research development of bone metastases in prostate cancer: A 22-year study.

Background: Prostate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends. Methods: We searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords. Results: A total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa. Conclusions: mCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa.

Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer.

Background: Although TP53 and SPOP are frequently mutated in metastatic prostate cancer (PCa), their prognostic value is ambiguous, and large sample studies are lacking, especially when they co-occur with other genetic alterations. Methods: Genomic data and patients' clinical characteristics in PCa were downloaded from the cBioPortal database. We extensively analyzed other gene alterations in different mutation status of TP53 and SPOP. We further subdivided TP53 and SPOP mutation into subgroups based on different mutation status, and then evaluated the prognostic value. Two classification systems for TP53 survival analysis were used. Results: A total of 2,172 patients with PCa were analyzed in our study, of which 1,799 were metastatic PCa patients. The mutual exclusivity analysis showed that TP53 and SPOP mutation has a strong mutual exclusion (p<0.001). In multivariable analysis, truncating TP53 mutations (HR=1.773, 95%CI:1.403-2.239, p<0.001) and other TP53 mutations(HR=1.555, 95%CI:1.267-1.908, p<0.001) were independent negative prognostic markers in metastatic PCa, whereas SPOP mutations(HR=0.592, 95%CI:0.427-0.819, p<0.001) were an independent prognostic factor for better prognosis. Mutations in TP53 were significantly associated with wild-type status for SPOP and CDK12, structural variants/fusions for TMPRSS2 and ERG, AR amplification and PTEN deletion (p<0.001). And truncating TP53 mutations have higher AR amplification rates than other TP53 mutations (p=0.022). Consistently, truncating TP53 mutations had a worse prognosis than other TP53 mutations (p<0.05). Then Kaplan-Meier survival curve showed that Co-occurring TP53 mutations in AR amplification or PTEN deletion tumors significantly reduced survival (p<0.05). Furthermore, those with SPOP-mutant tumors with co-occurring TP53 truncating mutations had shorter overall survival than those with SPOP-mutant tumors with wild-type or other TP53 mutations. Conclusions: This study found that TP53 and SPOP mutations were mutually exclusive and both were independent prognostic markers for metastatic PCa. Genomic alteration and survival analysis revealed that TP53 and SPOP mutations represented distinct molecular subtypes. Our data suggest that molecular stratification on the basis of TP53 and SPOP mutation status should be implemented for metastatic PCa to optimize and modify clinical decision-making.

Efficient recovery of valuable metals from cathode materials of spent LiCoO2 batteries via co-pyrolysis with cheap carbonaceous materials.

Recovery of valuable metals from spent Li-ion batteries has prominent economic and environmental benefits. In this study, a novel approach for recycling valuable metals from spent LiCoO2 batteries via co-pyrolysis with three different carbonaceous materials (waste polyethylene, biomass, and coal)) was proposed and evaluated. The thermodynamic analysis proved that carbonaceous materials (mainly carbon) were theoretically able to facilitate the decomposition process of LiCoO2. The promotion effect on LiCoO2 decomposition was in the following order: coal > biomass > polyethylene, and the decomposition temperature of LiCoO2 could significantly reduce by 400 °C via adding coal. The char produced from the carbonaceous materials, rather than the volatiles, played an important role in LiCoO2 decomposition and reduction. The pyrolysis products of LiCoO2 and coal mixture exhibited typical superparamagnetism and hysteresis behaviours, which benefitted the subsequent magnetic separation. The recovery rates of Co and Li were sensitive to the pyrolysis temperature and residence time, respectively. A high proportion of Co was in the form of CoO below 800 °C and had not been completely reduced, leading to the relatively lower recovery rates of Co below 800 °C. The optimal recovery rates of Co (96.8%) and Li (88.7%) were obtained at the pyrolysis temperature of 800 °C and the residence time of 10 min. The final recovery products were Co and Li2CO3 with rather high crystallinities and purities. Therefore, this study provided a novel approach for the efficient recycling of valuable metals from spent Li-ion batteries with high application prospects.

UBE2S as a novel ubiquitinated regulator of p16 and ß-catenin to promote bone metastasis of prostate cancer.

Bone metastasis is the main site of metastasis and causes the most deaths in patients with prostate cancer (PCa). The mechanism of bone metastasis is complex and not fully clarified. By RNA sequencing and analysing key pathways in bone metastases of PCa, we found that one of the most important characteristics during PCa bone metastasis was G1/S transition acceleration caused by low protein levels of p16INK4a (p16). Interestingly, we demonstrated that UBE2S bound and degraded p16 through K11- rather than K48- or K63-linked ubiquitination, which accelerated PCa tumour cell G1/S transition in vivo and in vitro. Moreover, UBE2S also stabilized ß-catenin through K11-linked ubiquitination, leading to enhanced migration and invasion of tumour cells in PCa bone metastasis. Based on our cohorts and public databases, UBE2S was overexpressed in bone metastases and positively correlated with a high Gleason score, advanced nodal metastasis status and poor prognosis in PCa. Finally, targeting UBE2S with cephalomannine inhibited proliferation and invasion in vitro, and bone metastasis of PCa in vivo. This study innovatively discovered that UBE2S plays an oncogenic role in bone metastasis of PCa by degrading p16 and stabilizing ß-catenin via K11-linked ubiquitination, suggesting that it may serve as a multipotent target for metastatic PCa treatment.

Suprapubic Transvesical Repair of Vesicovaginal Fistula Using a Homemade Laparoscopic Single-Port Device: Experience of 42 Patients.

Aim: Vesicovaginal fistula (VVF) is the most common urogenital acquired fistula, and has remained a scourge and of public health importance. VVF can be repaired by transvaginal approach, transabdominal approach or transvesical approach, but the optimal management is still debated. Methods: To demonstrate a suprapubic transvesical approach to repair VVFs using a homemade laparoscopic single-port device. A retrospective review of the medical records of 42 consecutive patients who underwent fistula repair for VVF at our center from January 2012 to March 2018 was performed. VVFs were repaired by a suprapubic transvesical approach using a homemade laparoscopic single-port device. Clinical data, perioperative data and outcomes were collected. The primary outcome was VVF successful closure rate, and secondary outcome was perioperative complications. Results: The mean age of the patients was 44.6 (27-58) yr. The mean follow-up time was 65.6 (32-118) mo. The VVFs were successfully closed in 37 (88.1%) patients after the first surgery, and failure was observed in five patients. Initial failures of all the five patients were cured after a second repair. No major complication occurred as defined by Clavien-Dindo class 2 or greater. Conclusions: Suprapubic transvesical approach to repair VVFs using a homemade laparoscopic single-port device is a simple, effective, and feasible approach offering ideal results without major complications.

A novel method for carbon removal and valuable metal recovery by incorporating steam into the reduction-roasting process of spent lithium-ion batteries.

Oxygen-free roasting could efficiently achieve the recovery of valuable metals from spent lithium-ion batteries (LIBs), but the roasted products have the drawbacks of a high carbon (C) content and a complex separation process. Hence, in this study, a new method incorporating steam (H2O) into the reduction-roasting recovery process of spent LIBs (steam roasting) was proposed to realize carbon removal and valuable metal recovery simultaneously. The influence of steam on the reduction-roasting process of spent LiNi0.6Co0.2Mn0.2O2 batteries (NCM) was investigated through experimental methods and thermodynamic analysis. The results indicated that the addition of steam could dramatically facilitate the decomposition and reduction process of spent NCM, and the carbon removal efficiency could reach 84%. H2O only acted on the reaction process of the anode material, and the main component C could be efficiently gasified by steam to produce hydrogen (H2) and carbon monoxide (CO), which could significantly accelerate the reduction process of CoO and NiO. The optimal conditions for valuable metal recovery and carbon removal were a H2O/C mole ratio of 5:1 and a reduction-roasting temperature of 1123 K. After steam roasting, the magnetic recovery efficiencies of Co and Ni were as high as 90% and 93%, respectively. The final recovery products were Co, Ni, and Li2CO3 with high purities. Therefore, this study is expected to provide a novel approach to achieve efficient disposal and recovery of metals from spent LIBs.

B7 score and T cell infiltration stratify immune status in prostate cancer.

BACKGROUND: Although immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa. METHODS: Immunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8+ and Foxp3+ lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs), were explored. RESULTS: HHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8+ TILs. Importantly, a new immune classification, based on the B7 score and CD8+ TILs, successfully stratified OS and CSS in PCa. CONCLUSIONS: Both B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.

The metastatic promoter DEPDC1B induces epithelial-mesenchymal transition and promotes prostate cancer cell proliferation via Rac1-PAK1 signaling.

Metastasis is the major cause of prostate cancer (PCa)-related mortality. Epithelial-mesenchymal transition (EMT) is a vital characteristic feature that empowers cancer cells to adapt and survive at the beginning of metastasis. Therefore, it is essential to identify the regulatory mechanism of EMT in metastatic prostate cancer (mPCa) and to develop a novel therapy to block PCa metastasis. Here, we discovered a novel PCa metastasis oncogene, DEP domain containing 1B (DEPDC1B), which was positively correlated with the metastasis status, high Gleason score, advanced tumor stage, and poor prognosis. Functional assays revealed that DEPDC1B enhanced the migration, invasion, and proliferation of PCa cells in vitro and promoted tumor metastasis and growth in vivo. Mechanistic investigations clarified that DEPDC1B induced EMT and enhanced proliferation by binding to Rac1 and enhancing the Rac1-PAK1 pathway. This DEPDC1B-mediated oncogenic effect was reversed by a Rac1-GTP inhibitor or Rac1 knockdown. In conclusion, we discover that the DEPDC1B-Rac1-PAK1 signaling pathway may serve as a multipotent target for clinical intervention in mPCa.