Novel phosphatase PvPAP1 from the As-hyperaccumulator Pteris vittata promotes organic P utilization and plant growth: Extracellular exudation and phytate hydrolysis.

Organic phosphorus (Po) is a large component of soil P, but it is often unavailable for plant uptake. Purple acid phosphatases (PAP) can hydrolyze a wide range of Po, playing an important role in Po utilization by plants. In this study, we investigated a novel secretary PvPAP1 from the As-hyperaccumulator Pteris vittata, which can effectively utilize exogenous Po, including adenosine triphosphate (ATP) and phytate. Unlike other PAP, PvPAP1 was abundantly-expressed in P. vittata roots, which was upregulated 3.5-folds under P-deprivation than P-sufficient conditions. When expressed in tobacco, its activity in the roots of PvPAP1-Ex lines was ∼8 folds greater than that in wild-type (WT) plants. Besides, PvPAP1 exhibited its secretory ability as evidenced by the sapphire-blue color on the root surface after treating with 5-bromo-4-chloro-3-indolyl phosphate. In a long-term experiment using sand media, PvPAP1-expressing tobacco plants showed 25-30 % greater root biomass than WT plants when using ATP as the sole P source. This is because PvPAP1-expression enhanced its phosphatase activity by 6.5-9.2 folds in transgenic tobacco, thereby increasing the P contents by 39-41 % in its roots under ATP treatment and 9.4-30 % under phytate treatment. The results highlight PvPAP1 as a novel secreted phosphatase crucial for external Po utilization in P. vittata, suggesting that PvPAP1 has the potential to serve as a valuable gene resource for enhancing Po utilization by crop plants.

Arsenite Antiporter PvACR3 Driven by Its Native Promoter Increases Leaf Arsenic Accumulation in Tobacco.

Pteris vittata is the first-reported arsenic (As) hyperaccumulator, which has been applied to phytoremediation of As-contaminated soil. PvACR3, a key arsenite (AsIII) antiporter, plays an important role in As hyperaccumulation in P. vittata. However, its functions in plants are not fully understood. In this study, the PvACR3 gene was heterologously expressed in tobacco, driven by its native promoter (ProPvACR3). After growing at 5 µM AsIII or 10 µM AsV in hydroponics for 1-5 days, PvACR3-expression enhanced the As levels in leaves by 66.4-113 and 51.8-101%, without impacting the As contents in the roots or stems. When cultivated in As-contaminated soil, PvACR3-expressed transgenic plants accumulated 47.9-85.5% greater As in the leaves than wild-type plants. In addition, PvACR3-expression increased the As resistance in transgenic tobacco, showing that enhanced leaf As levels are not detrimental to its overall As tolerance. PvACR3 was mainly expressed in tobacco leaf veins and was likely to unload AsIII from the vein xylem vessels to the mesophyll cells, thus elevating the leaf As levels. This work demonstrates that heterologously expressing PvACR3 under its native promoter specifically enhances leaf As accumulation in tobacco, which helps to reveal the As-hyperaccumulation mechanism in P. vittata and to enhance the As accumulation in plant leaves for phytoremediation.

The Influence of Al and Nb on the Low Oxygen Pressure Pre-Oxidation Behavior of Fe-35Ni-20Cr-xAl-yNb Alloys at 1000 °C.

To investigate the impact of Al and Nb elements on the formation of a protective oxide layer on the surface of Fe-35Ni-20Cr-xAl-yNb (x = 0, 2, 4, 6 wt.%; y = 0, 1, 2 wt.%) alloys, their oxidation behavior was examined at 1000 °C, 10-17 atm. and 10-25 atm. oxygen pressure, and the oxidation mechanism was analyzed by Factsage and Pandat calculations. Enhancing the Al content at 10-17 atm. inhibited the generation of FeCr2O4 on the alloy surface and increased the Al content in the M2O3 layer. When the Al content exceeded 6 wt.%, the oxide film partially peeled off. It was found that the addition of Nb increased the activity of Cr and Al and decreased the activity of Ni and Fe and promoted the formation of Al2O3, and the appearance of Nb2O5 in the subsurface layer increased the density of the oxide film. In addition, under an oxygen pressure of 10-25 atm., the only protective layer on the surface of the alloy comprised of Al2O3. The experimental results demonstrated that the Fe-35Ni-20Cr-4Al-2Nb alloy generated a continuous and dense Al2O3 protective film, and the reduction in oxygen pressure and the addition of Nb elements were favorable for selective external oxidation of Al2O3.

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.

Using Fe biofortification strategies to reduce both Ni concentration and oral bioavailability for rice with high Ni.

Due to naturally high Ni or soil Ni contamination, high Ni concentrations are reported in rice, raising a need to reduce rice Ni exposure risk. Here, reduction in rice Ni concentration and Ni oral bioavailability with rice Fe biofortification and dietary Fe supplementation was assessed using rice cultivation and mouse bioassays. Results showed that for rice grown in a high geogenic Ni soil, increases in rice Fe concentration from ∼10.0 to ∼30.0 µg g-1 with foliar EDTA-FeNa application led to decreases in Ni concentration from ∼4.0 to ∼1.0 µg g-1 due to inhibited Ni transport from shoot to grains via down-regulated Fe transporters. When fed to mice, Fe-biofortified rice was significantly (p < 0.01) lower in Ni oral bioavailability (59.9 ± 11.9% vs. 77.8 ± 15.1%; 42.4 ± 9.81% vs. 70.4 ± 6.81%). Dietary amendment of exogenous Fe supplements to two Ni-contaminated rice samples at 10-40 µg Fe g-1 also significantly (p < 0.05) reduced Ni RBA from 91.7% to 61.0-69.5% and from 77.4% to 29.2-55.2% due to down-regulation of duodenal Fe transporter expression. Results suggest that the Fe-based strategies not only reduced rice Ni concentration but also lowered rice Ni oral bioavailability, playing dual roles in reducing rice-Ni exposure.

Microplastics are transferred by soil fauna and regulate soil function as material carriers.

The ecotoxicological effects of microplastics, a new and widespread ecosystem pollutant, have been extensively reported. However, it remains unclear whether soil fauna transfer microplastics and whether migration behaviours influence subsequent ecological functions in terrestrial ecosystems. We investigated the transfer patterns of microplastics and their adsorbed substances by soil animals (the springtail, Folsomia candida) and the effect of the transfer on the decomposition of soil organic matter through a standardized cotton strip assay. The results showed that springtails had a strong ability to transfer microplastics into the soil. The adsorbed nutrient (nitrogen; N), pollutant (cadmium; Cd), and green fluorescent Escherichia coli (GFP-E. coli) were also transferred with the microplastics. In addition, cotton strip decomposition was accelerated when the microplastics adsorbed N, but the adsorption of Cd decreased decomposition. These ecological effects were particularly strong for small microplastics. Microplastic transfer regulated soil bacterial communities, promoting the growth of Ascomycota fungi and inhibiting that of Basidiomycota, leading to cotton strip decomposition. Thus, microplastic pollution may occur at one site, but microplastics can be transferred anywhere in terrestrial ecosystems by soil animals and adsorb other substances, including nutrients and pollutants, that affect ecosystem function. Therefore, more studies on the migration behaviour of microplastics are necessary.

Degradable Pure Magnesium Used as a Barrier Film for Oral Bone Regeneration.

The barrier membrane plays an extremely critical role in guided bone regeneration (GBR), which determines the success or failure of GBR technology. In order to obtain barrier membranes with high mechanical strength and degradability, some researchers have focused on degradable magnesium alloys. However, the degradation rate of pure Mg-based materials in body fluids is rather fast, thus posing an urgent problem to be solved in oral clinics. In this study, a novel micro-arc oxidation (MAO) surface-treated pure Mg membrane was prepared. Electrochemical tests, immersion experiments and in vivo experiments were carried out to investigate its potential use as a barrier membrane. The experimental results showed that the corrosion resistance of a pure Mg membrane treated by MAO is better than that of the uncoated pure Mg. The results of cell experiments showed no obvious cytotoxicity, which suggests the enhanced differentiation of osteoblasts. At the same time, the MAO-Mg membrane showed better biological activity than the pure Ti membrane in the early stage of implantation, exhibiting relatively good bone regeneration ability. Consequently, the MAO membrane has been proven to possess good application prospects for guided bone regeneration.

Profile of chimeric RNAs and TMPRSS2-ERG e2e4 isoform in neuroendocrine prostate cancer.

PURPOSE: Specific gene fusions and their fusion products (chimeric RNA and protein) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric RNAs have been conducted in neuroendocrine prostate cancer (NEPC). In this study, we explored the landscape of chimeric RNAs in different types of prostate cancer (PCa) cell lines and aimed to identify chimeric RNAs specifically expressed in NEPC. METHODS: To do so, we employed the RNA-seq data of eight prostate related cell lines from Cancer Cell Line Encyclopedia (CCLE) for chimeric RNA identification. Multiple filtering criteria were used and the candidate chimeric RNAs were characterized at multiple levels and from various angles. We then performed experimental validation on all 80 candidates, and focused on the ones that are specific to NEPC. Lastly, we studied the clinical relevance and effect of one chimera in neuroendocrine process. RESULTS: Out of 80 candidates, 15 were confirmed to be expressed preferentially in NEPC lines. Among them, 13 of the 15 were found to be specifically expressed in NEPC, and four were further validated in another NEPC cell line. Importantly, in silico analysis showed that tumor malignancy may be correlated to the level of these chimeric RNAs. Clinically, the expression of TMPRSS2-ERG (e2e4) was elevated in tumor tissues and indicated poor clinical prognosis, whereas the parental wild type transcripts had no such association. Furthermore, compared to the most frequently detected TMPRSS2-ERG form (e1e4), e2e4 encodes 31 more amino acids and accelerated neuroendocrine process of prostate cancer. CONCLUSIONS: In summary, these findings painted the landscape of chimeric RNA in NEPC and supported the idea that some chimeric RNAs may represent additional biomarkers and/or treatment targets independent of parental gene transcripts.

Systems, Properties, Surface Modification and Applications of Biodegradable Magnesium-Based Alloys: A Review.

In recent years, biodegradable magnesium (Mg) alloys have attracted the attention of many researchers due to their mechanical properties, excellent biocompatibility and unique biodegradability. Many Mg alloy implants have been successfully applied in clinical medicine, and they are considered to be promising biological materials. In this article, we review the latest research progress in biodegradable Mg alloys, including research on high-performance Mg alloys, bioactive coatings and actual or potential clinical applications of Mg alloys. Finally, we review the research and development direction of biodegradable Mg alloys. This article has a guiding significance for future development and application of high-performance biodegradable Mg alloys, promoting the future advancement of the magnesium alloy research field, especially in biomedicine.

Effects of Different Rare Earth Elements on the Degradation and Mechanical Properties of the ECAP Extruded Mg Alloys.

Effects of different rare earth elements on the degradation and mechanical properties of the ECAP (equal channel angular pressing) extruded Mg alloys were investigated in this work. Microstructural characterization, thermodynamic calculation, a tensile test, an electrochemical test, an immersion test, a hydrogen evolution test and a cytotoxicity test were carried out. The results showed that yttrium addition was beneficial to the improvement of the alloy's strength, and the ultimate tensile strength (UTS) and yield strength (YS) values of the ECAPed Mg-2Zn-0.5Y-0.5Zr alloy reached 315 MPa and 295 MPa, respectively. In addition, Nd was beneficial to the corrosion resistance, for which, the corrosion rate of the ECAPed Mg-2Zn-0.5Nd-0.5Zr alloy was observed to be 0.42 ± 0.04 mm/year in Hank's solution after 14 days of immersion. Gd was moderate in improving both the corrosion resistance and mechanical properties. Moreover, after co-culturing with murine calvarial preosteoblasts (MC3T3-E1) cells, the ECAPed Mg-2Zn-0.5RE (Nd, Gd, Y)-0.5Zr alloys exhibited good cytocompatibility with a grade 1 cytotoxicity. Consequently, the ECAPed Mg-2Zn-0.5Nd-0.5Zr alloy showed the best application prospect in the field of orthopedics.

Immune Signatures Combined With BRCA1-Associated Protein 1 Mutations Predict Prognosis and Immunotherapy Efficacy in Clear Cell Renal Cell Carcinoma.

Immunotherapy is gradually emerging in the field of tumor treatment. However, because of the complexity of the tumor microenvironment (TME), some patients cannot benefit from immunotherapy. Therefore, we comprehensively analyzed the TME and gene mutations of ccRCC to identify a comprehensive index that could more accurately guide the immunotherapy of patients with ccRCC. We divided ccRCC patients into two groups based on immune infiltration activity. Next, we investigated the differentially expressed genes (DEGs) and constructed a prognostic immune score using univariate Cox regression analysis, unsupervised cluster analysis, and principal component analysis (PCA) and validated its predictive power in both internal and total sets. Subsequently, the gene mutations in the groups were investigated, and patients suitable for immunotherapy were selected in combination with the immune score. The prognosis of the immune score-low group was significantly worse than that of the immune score-high group. The patients with BRCA1-associated protein 1 (BAP1) mutation had a poor prognosis. Thus, this study indicated that establishing an immune score model combined with BAP1 mutation can better predict the prognosis of patients, screen suitable ccRCC patients for immunotherapy, and select more appropriate drug combinations.

Growth Kinetics of Bacillus pasteurii in Solid-Free Drilling Fluids.

A broken stratum is a complex stratum often encountered during drilling. Under erosion of the drilling fluid and disturbance of the drill pipe string, the rock in the well wall of the broken stratum is prone to collapsing and falling off, causing the well wall to lose its stability. Improving the cementing force between the broken blocks and forming a complete well wall are essential for overcoming this instability. The present study combined microbially induced calcite precipitation technology with solid-free drilling fluid technology for the first time to formulate a drilling fluid to overcome the instability of the well wall of a broken stratum. However, first and foremost, the growth of microorganisms in drilling fluids must be elucidated. To this end, experimental and theoretical analyses were performed to examine Bacillus pasteurii growth in drilling fluids composed of a single agent or combinations of various materials, such as a zwitterionic coating agent (FA367), a biopolymer (XC), a polyacrylate polymer (PAC-LV), and potassium polyacrylate (K-PAM). Experimental B. pasteurii growth data were then fitted using a modified Gompertz model. The mean square error indicated that the generated model had a reasonable degree of fit, and the bias and accuracy factors showed that the model could predict B. pasteurii growth. Among the different drilling fluid combinations used, suitable fluids for B. pasteurii growth were XC alone, XC, and PAC-LV in the two-material-based fluid and FA367, XC, and K-PAM in the three-material-based fluid. These results provide a solid foundation for the development of microbial drilling fluids to solve instability problems in broken geological formations.

Recent Advances on Development of Hydroxyapatite Coating on Biodegradable Magnesium Alloys: A Review.

The wide application of magnesium alloys as biodegradable implant materials is limited because of their fast degradation rate. Hydroxyapatite (HA) coating can reduce the degradation rate of Mg alloys and improve the biological activity of Mg alloys, and has the ability of bone induction and bone conduction. The preparation of HA coating on the surface of degradable Mg alloys can improve the existing problems, to a certain extent. This paper reviewed different preparation methods of HA coatings on biodegradable Mg alloys, and their effects on magnesium alloys' degradation, biocompatibility, and osteogenic properties. However, no coating prepared can meet the above requirements. There was a lack of systematic research on the degradation of coating samples in vivo, and the osteogenic performance. Therefore, future research can focus on combining existing coating preparation technology and complementary advantages to develop new coating preparation techniques, to obtain more balanced coatings. Second, further study on the metabolic mechanism of HA-coated Mg alloys in vivo can help to predict its degradation behavior, and finally achieve controllable degradation, and further promote the study of the osteogenic effect of HA-coated Mg alloys in vivo.

Novel PvACR3;2 and PvACR3;3 genes from arsenic-hyperaccumulator Pteris vittata and their roles in manipulating plant arsenic accumulation.

Arsenite (AsIII) antiporter ACR3 is crucial for arsenic (As) translocation and sequestration in As-hyperaccumulator Pteris vittata, which has potential for phytoremediation of As-contaminated soils. In this study, two new ACR3 genes PvACR3;2 and PvACR3;3 were cloned from P. vittata and studied in model organism yeast (Saccharomyces cerevisiae) and model plant tobacco (Nicotiana tabacum). Both ACR3s mediated AsIII efflux in yeast, decreasing its As accumulation and enhancing its As tolerance. In addition, PvACR3;2 and PvACR3;3 were expressed in tobacco plant. Localized on the plasma membrane, PvACR3;2 mediated both AsIII translocation to the shoots and AsIII efflux from the roots in tobacco, resulting in 203 - 258% increase in shoot As after exposing to 5 µM AsIII under hydroponics. In comparison, localized to the vacuolar membrane, PvACR3;3 sequestrated AsIII in tobacco root vacuoles, leading to 18 - 20% higher As in the roots and 15 - 36% lower As in the shoots. Further, based on qRT-PCR, both genes were mainly expressed in P. vittata fronds, indicating PvACR3;2 and PvACR3;3 may play roles in AsIII translocation and sequestration in the fronds. This study provides not only new insights into the functions of new ACR3 genes in P. vittata, but also important gene resources for manipulating As accumulation in plants for phytoremediation and food safety.

Microplastics with cadmium inhibit the growth of Vallisneria natans (Lour.) Hara rather than reduce cadmium toxicity.

Microplastics and heavy metals are discharged into a freshwater environment either directly or via surface runoff and are largely deposited in sediments, posing risks to aquatic organisms. Few studies have thus far been devoted to the interaction of microplastics and heavy metals in sediments. Whether microplastics can affect the toxicity and accumulation of heavy metals in submerged macrophytes remains unclear. We evaluated the effects of polyvinyl chloride microplastics (PVC-MPs) and cadmium (Cd) exposure levels (0, 5, 15, and 25 mg) on Vallisneria natans (Lour.) Hara grown in sediment in a microcosm experiment for 14 d. In this study, PVC-MPs decreased the fresh weights of V. natans in the absence of Cd and markedly reduced the fresh weights at 5 and 15 mg Cd exposure levels. Moreover, PVC-MPs substantially increased the malondialdehyde (MDA) content of V. natans leaves at a Cd exposure of 25 mg. However, the PVC-MPs neither reduced the Cd concentration nor independently increased the antioxidant enzyme activities of the plants. These findings indicate that microplastics can independently, or jointly with a Cd contaminant, inhibit the growth of submerged macrophytes rather than reduce Cd toxicity. To our knowledge, this study is the first to evaluate the effects of microplastics and Cd exposure in sediments on the growth and physiological traits of submerged macrophytes, which could provide important implications for the interaction and future risk assessment of microplastics and heavy metals in sediments of freshwater ecosystems.

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.

Efficient arsenate reduction in As-hyperaccumulator Pteris vittata are mediated by novel arsenate reductases PvHAC1 and PvHAC2.

Arsenic-hyperaccumulator Pteris vittata is efficient in As absorption, reduction, and translocation. But the molecular mechanisms and locations of arsenate (AsV) reduction in P. vittata are still unclear. Here, we identified two new arsenate reductase genes from P. vittata, PvHAC1 and PvHAC2. Two PvHAC genes encoded a rhodanase-like protein, which were localized in the cytoplasm and nucleus. Both recombinant Escherichia coli strains and transgenic Arabidopsis thaliana lines showed arsenate reductase ability after expressing PvHAC genes. Further, expressing PvHAC2 enhanced As tolerance and reduced As accumulation in A. thaliana shoots under AsV exposure. Based on expression pattern analysis, PvHAC1 and PvHAC2 were predominantly expressed in the rhizomes and fronds of P. vittata. Different from those of HAC homologous genes in non-hyperaccumulators, little PvHAC was expressed in the roots. Besides, PvHAC1 expression was strongly upregulated under AsV exposure but not AsIII. The data suggest that arsenate reductase PvHAC1 in the rhizomes coupled with arsenate reductase PvHAC2 in the fronds of P. vittata played a critical role in As-hyperaccumulation by P. vittata, which helps to further improve its utility in phytoremediation of As-contaminated soils.

Immune Cytolytic Activity as an Indicator of Immune Checkpoint Inhibitors Treatment for Prostate Cancer.

Immune checkpoint inhibitors (ICIs) treatment is becoming a new hope for cancer treatment. However, most prostate cancer (PCa) patients do not benefit from it. In order to achieve the accuracy of ICIs treatment in PCa and reduce unnecessary costs for patients, we have analyzed the data from TCGA database to find a indicator that can assist the choice of treatment. By analyzing the data of PCa patients with TMB analysis and immune infiltration analysis, we found the expression of immune cells in different immune infiltration groups. Commonly used markers of ICIs, expressed on CD8+ T cell, were highly expressed in the high immune group. Then we used the forimmune cytolytic activity (CYT) to determine its relationship with the target of ICIs treatment. Through the analysis of CYT score and the ligands of immune checkpoints, we found that there was a significant correlation between them. With the increase of CYT score, the expression of CD80/86, PD-L1/L2, TNFSF14, and LGALS9 also increased gradually. Similarly, CD8+ T cells were significantly increased in the CYT high group compared with the CYT low group in PRAD. The present research provides novel insights into the immune microenvironment of PRAD and potential immunotherapies. The proposed CYT score is a clinically promising indicator that can serve as a marker to assist anti-PD-L1 or other ICIs treatment. At the same time, it also provides a basis for the selection of other immune checkpoint drugs.

Topoisomerase II-binding protein 1 promotes the progression of prostate cancer via ATR-CHK1 signaling pathway.

DNA damage response (DDR) plays an important role in the progression of cancers, including prostate cancer (PCa). Topoisomerase II-binding protein 1 (TopBP1) is an essential promotor of ATR-mediated DDR. Herein, we investigated the association between TopBP1 and PCa and determined its effect on the progression of PCa. The expression and clinical features of TopBP1 were analyzed using large-scale cohort of tissue microarray analyses and The Cancer Genome Atlas database, which indicated that TopBP1 was positively correlated with high Gleason Score, advanced clinical and pathological stages, the metastasis status. Multivariate analysis revealed that the upregulation of TopBP1 was an independent predictor for a worse biochemical recurrence-free survival (BCR-free survival). Furthermore, we discovered that downregulation of TopBP1 significantly suppressed the growth and migration ability of PCa lines by loss-of-function assays in vitro. Further mechanistic investigations clarified that TopBP1 promoted proliferation and migration by activating ATR-Chk1 signaling pathway.