A magnetic calcium phosphate for selective capture of multi-phosphopeptides.

The specific enrichment of multi-phosphopeptides in the presence of non-phosphopeptides and mono-phosphopeptides was still a challenge for phosphoproteomics research. Most of these enrichment materials relied on Zn, Ti, Sn, and other rare precious metals as the bonding center to enrich multi-phosphopeptides while ignoring the use of common metal elements. The addition of rare metals increased the cost of the experiment, which was not conducive to their large-scale application in biomedical proteomics laboratories. In addition, multiple high-speed centrifugation steps also resulted in the loss of low-abundance multi-phosphopeptides in the treatment procedure of biological samples. This study proposed the use of calcium, a common element, as the central bonding agent for synthesizing magnetic calcium phosphate materials (designated as CaP-Fe3O4). These materials aim to capture multi-phosphopeptides and identifying phosphorylation sites. The current results demonstrate that CaP-Fe3O4 exhibited excellent selection specificity, high sensitivity, and stability in the enrichment of multi-phosphopeptides and the identification of phosphorylation sites. Additionally, the introduction of magnetic separation not only reduced the time required for multi-phosphopeptides enrichment but also prevented the loss of these peptides during high-speed centrifugation. These findings contribute to the widespread application and advancement of phosphoproteomics research.

The prognostic significance and clinical relevance of stem cell characteristic in bladder cancer.

Background: Bladder cancer (BLCA) is a common malignant tumor of urinary system and prognostic biomarkers are needed for better clinical decision-making and patient management. Cancer stem cells (CSCs) are involved in carcinogenesis, development, metastasis and recurrence of BLCA. This study explored the prognostic and predictive value of CSCs-related genes and laid the groundwork for precision treatment development in BLCA. Methods: The mRNA data and corresponding clinical information obtained from TCGA-BLCA cohort was used to discover biomarkers and develop CSCs-related prognostic model, which was further validated in GSE32548 and GSE32894 datasets. In addition, the association between CSCs-related risk score and therapeutic efficacy was analyzed to explore the potential predictive value of the prognostic model. Results: We identified four CSCs-related subtypes and 900 differentially expressed genes (DEGs) among subtypes. Then the CSCs-related prognostic model was built based on 16 CSCs-related DEGs with the most significant prognostic value. Patients in the low-risk group had better overall survival than those in high-risk group (P < 0.001; HR, 0.42; 95 %CI, 0.31-0.57). Multivariable Cox analysis in training and test sets confirmed the independence of CSCs-related risk score as a prognostic factor (P < 0.05). The difference of survival between two risk groups were probably due to the significantly varied immune microenvironment based on the analysis of infiltrated immune cells. Additionally, the risk score was significantly associated with chemotherapy sensitivity and the response to anti-PD-L1 therapy (P < 0.05) which suggested a potential predictive value of CSCs-related risk model. Conclusion: We established a risk classifier based on 16 CSCs-related genes for predicting survival in patients with BLCA. The CSCs-related risk model has both prognostic value and potential predictive value for therapeutic efficacy, which brings us closer to understanding the important role of CSCs in BLCA and may provide guidance for clinical treatment decision-making and patient management. The clinical utility of the CSCs-related risk classifier warrants further studies.

Identification of a novel stemness-related signature with appealing implications in discriminating the prognosis and therapy responses for prostate cancer.

PURPOSE: Cancer stemness represents the tumor-initiation and self-renewal potentials of cancer stem cells. It is involved in prostate cancer progression and resistance to therapy. Herein, we aimed to unveil the stemness features, establish a novel prognostic model, and identify potential therapeutic targets. METHODS: 26 stemness-related signatures were obtained from StemChecker. The expression profiles and clinical traits of TCGA-PRAD were obtained from TCGA and cBioPortal, respectively. GSE5446 and GSE70769 cohorts were acquired from GEO. PRAD_MSKCC cohort was also retrieved via the cBioPortal. The consensus clustering method was used for stemness subclusters classification. WGCNA was used to identify hub genes related to the stemness subcluster. The most important feature was explored in vitro. RESULTS: Prostate cancer patients of TCGA-PRAD were divided into two subclusters (C1 and C2) based on the enrichment scores of the 26 stemness-related signatures. C1 was characterized by decreased survival, rich infiltrations of M0 macrophages and regulatory T cells, minimum sensitivity to chemotherapy, and a low response to immunotherapy. Hub genes of the red module with the highest correlation with C1 were subsequently identified by WGCNA and subjected to stemness-related risk model construction based on the machine-learning framework. Prostate cancer patients with high stemness scores had unfavorable prognosis, immunosuppressive tumor microenvironment, minimum sensitivity to chemotherapy, and a low response to immunotherapy. MXD3, the most important factor of the model, can regulate the stemness traits of prostate cancer cells. CONCLUSIONS: Our study depicted the stemness landscapes of prostate cancer and characterized two subclusters with diverse prognoses and tumor immune microenvironments. A stemness-risk signature was developed and demonstrated prospective implications in predicting prognosis and precision medicine.

Laser-activated nanoparticles for ultrasound/photoacoustic imaging-guided prostate cancer treatment.

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo. In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects.

Sonosensitive Phase-Changeable Nanoparticle Mediated Enhanced Chemotherapy in Prostate Cancer by Low-Intensity Focused Ultrasound.

Prostate cancer (PCa) is one of the most common cancer types. Early detection of PC offers the best chance of successful treatment. A noninvasive, image-guided therapy mediated by targeted nanoparticles (NPs) has the potential to improve the efficacy and safety of cancer therapies. Herein, we report a sonosensitive nanoparticle modified with anti-PSMA (prostate-specific membrane antigen) antibodies to activate target prostate tumors. These nanoparticles (PFP@IR780@PTX@liposome NPs) were co-loaded with the chemotherapeutic agent docetaxel and the sonosensitizer IR780, as well as phase-changeable perfluorocarbon (PFC) liquids. The liquid-gas phase change could be induced by low-intensity focused ultrasound (LIFU) in vitro. We found that the PFP@IR780@PTX@liposome NPs can specifically accumulate in prostate tumors after LIFU irradiation, as monitored by ultrasound and photoacoustic imaging. Meanwhile, docetaxel was controllably released from the nanoparticles to achieve enhanced chemotherapeutic therapy in vivo. These sonosensitive phase-changeable NPs can visually treat prostate cancers effectively and have a clinical potential.

Comprehensive Landscape of HOXA2, HOXA9, and HOXA10 as Potential Biomarkers for Predicting Progression and Prognosis in Prostate Cancer.

Prostate cancer (PCa) is recognized as a common malignancy in male patients. The homeobox A cluster (HOXA) family members have been confirmed to be implicated in the development of several types of tumors. However, the expression pattern and prognostic values of HOXA genes in PCa have not been investigated. In this study, we analyzed TCGA datasets and identified six HOXA family members which showed a dysregulated expression in PCa specimens compared with nontumor specimens. We also explored the potential mechanisms involved in the dysregulation of HOXA family members in PCa, and the results of Pearson's correlation revealed that most HOXA members were negatively related to the methylation degree. Moreover, we explored the prognostic values of HOXA family members and identified six survival-related HOXA members. Importantly, HOXA2, HOXA9, and HOXA10 were identified as critical PCa-related genes which were abnormally expressed in PCa and associated with clinical outcomes of PCa patients. Then, we explored the association between the above three genes and immune cell infiltration. We observed that the levels of HOXA2, HOXA9, and HOXA10 were associated with the levels of immune infiltration of several kinds of immune cells. Overall, our findings identified the potential values of the HOXA family for outcome prediction in PCa, which might facilitate personalized counselling and treatment in PCa.

Efficacy and safety of Prostate stereotactic body radiotherapy for metastatic castration-resistant prostate cancer: A prospective cohort study.

BACKGROUND: The efficacy and safety of prostate SBRT in men with mCRPC is unknown. MATERIALS AND METHODS: A prospective cohort study was conducted with 125 men diagnosed with mCRPC. All patients received ADT plus chemotherapy. Patients were randomly assigned to receive daily prostate SBRT (36-48 Gy in 6-8 fractions). Patients who did not receive SBRT served as controls. RESULTS: The primary endpoints were PFS and OS. After 89 months of total follow-up, the median PFS was 13.8 months in the SBRT group (n = 61) and 12.0 months in the control group (n = 64) (HR, 0.87; 95% CI, 0.61-1.24; P = 0.249). The OS was 25.7 months in the SBRT group and 23.8 months in the control group (HR, 0.93; 95% CI, 0.65-1.33; P = 0.230). A non-significant increase in the PSA response rate (50.8% vs. 43.7%) and time to PSA progression (8.3 months vs. 7.0 months) was observed in the SBRT group compared to the control group; however, the time to symptomatic progression was significantly prolonged in the SBRT group (11.3 months) compared to the control group (8.5 months) (HR, 0.76; 95% CI, 0.53-1.08; P = 0.019). There was an 11.5% incidence of radiation cystitis and radiation rectitis in the SBRT group, and the degree and incidence of hormone-related and chemotherapy-related adverse events were similar between the two groups. CONCLUSION: Adding prostate SBRT significantly prolonged the time to symptomatic progression and non-significantly prolonged PFS and OS among men with mCRPC compared to treatment with ADT plus chemotherapy alone.

Highly selective enrichment of phosphopeptides using Zr4+-immobilized Titania nanoparticles.

It is urgent to selectively enrich trace phosphorylated proteins or peptides from complex biological sample for mass spectrometry (MS)-based phosphoproteomics. In this study, a novel immobilized metal affinity chromatography (IMAC) material with DOTA(1,4,7,10-tetraazacyclododecane N, N', N'', N'''-tetra-acetic acid) coated on the surface of TiO2 nanomaterials and functionalized with the metal ion Zr4+(TiO2@DOTA-Zr) has been synthesized successfully to improve the enrichment specificity and sensitivity for phosphopeptides. TiO2 nanomaterials were chosen as a support matrix, which will offer a high specific surface area to enhance the amounts of immobilized Zr4+ ions and will provide an additional selectivity for the special enrichment of phosphopeptides. Also, the introduction of DOTA will endow a stronger binding interaction between the Zr4+ ion and DOTA to reduce the loss of the metal ion Zr4+ during sample loading and washing steps. The novel TiO2@DOTA-Zr nanohybrids exhibited higher sensitivity and selectivity for phosphopeptides from the standard protein digests, the tryptic digests of nonfat milk and human serum, showing a great selective enrichment capability toward the complicated biological samples.

Hydrophilic modification of titania nanomaterials as a biofunctional adsorbent for selective enrichment of phosphopeptides.

TiO2-based metal oxide affinity chromatography (MOAC) nanomaterials show high potential in phosphoproteome mass-spectrometric (MS) analysis. However, a drawback of TiO2 nanomaterials is poor water solubility, which greatly reduces the enrichment efficiency of phosphopeptides and eventually limits their use in phosphoproteome MS analysis. In this work, a hydrophilic TiO2 hybrid material (denoted as NH2@TiO2) is successfully designed with 1,6-hexanediamine modified on the surface of TiO2 nanoparticles and applied as a biofunctional adsorbent for selective enrichment of phosphopeptides. The novel TiO2 hybrid material with high hydrophilicity and biocompatibility is characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and infrared (IR) spectroscopy, and its performance in selective enrichment of phosphopeptides is evaluated with the standard protein digests, human serum and the tryptic digests of nonfat milk.

Species diversity of corticolous myxomycetes in Tianmu Mountain National Nature Reserve, China.

The species diversity of corticolous myxomycetes on 4 vegetation types in the Tianmu Mountain National Natural Reserve, eastern China, was examined from 2011 to 2012. A total of 1440 moist chamber cultures were prepared with bark samples, which yielded several hundred collections representing 42 species in 20 genera. It was found that 79% of cultures produced some evidence (either plasmodia or fruiting bodies) of myxomycetes. Eight species (Comatricha elegans, Cribraria confusa, Licea pusilla, Cribraria microcarpa, Collaria arcyrionema, Licea biforis, Arcyria cinerea, and Clastoderma debaryanum) were abundant (exceeding 3% of all records), but about a third of all species were classified as rare. Species richness (S = 33) and diversity (exp[H'] = 16.60, S/G = 1.74) of corticolous myxomycetes were the most diverse in the deciduous broadleaf forest. The species recorded from coniferous forest showed the lowest species richness (S = 21) but the highest evenness (J' = 0.91). The cluster analyses were based on the Bray-Curtis similarity matrix, and the results indicated that corticolous myxomycete assemblages were distributed by a seasonal and annual pattern. Canonical correspondence analysis showed that season and pH were key factors in determining species distribution.

[Phylogenetic relationship between tufted deer(Elaphodus cephalophus) and Muntiacus deer is revealed by the exon and intron of K+ channel gene].

In this study, partial fragments of potassium ion channel gene were amplified using the genomic DNA of muntjak, reevesi, crinifrons, and Elaphodus cephalophus. The PCR products were ligated to the plasmid of pMD18-T Vector by the method of direct T-A cloning. The positive clones were identified by colony PCR. The sequences of the recombinant clones were determined using M13-47/RV-M universal primers and aligned by the software CLUSTALW. The nucleotide divergences of exon were 0.90%-1.44% among three species of Muntiacus, 0.90%-1.26% between E. cephalophus and each of Muntiacus deer. In the nucleotide of intron there is 0%-1.22% difference among these muntjac deers, and the divergene reached about 1.83% between E. cephalophus and the three species of Muntiacus. Using the software of MEGA to analyse molecular phylogeny, Phylogenetic trees were constructed with neighbor-joining method and maximum parsimony method. The result showed Muntiacus, crinifrons is most closely related to muntjak, with reevesi as their sister species. E. cephalophus is in the other genus.