To evaluate the performance of the Prostate Health Index (PHI) in magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion prostate biopsy for the detection of clinically significant ...prostate cancer (csPCa). We prospectively enrolled 164 patients with at least one Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) ≥ 3 lesions who underwent MRI-TRUS fusion prostate biopsy. Of the PSA-derived biomarkers, the PHI had the best performance in predicting csPCa (AUC 0.792, CI 0.707-0.877) in patients with PI-RADS 4/5 lesions. Furthermore, the predictive power of PHI was even higher in the patients with PI-RADS 3 lesions (AUC 0.884, CI 0.792-0.976). To minimize missing csPCa, we used a PHI cutoff of 27 and 7.4% of patients with PI-RADS 4/5 lesions could have avoided a biopsy. At this level, 2.0% of cases with csPCa would have been missed, with sensitivity and NPV rates of 98.0% and 87.5%, respectively. However, the subgroup of PI-RADS 3 was too small to define the optimal PHI cutoff. PHI was the best PSA-derived biomarker to predict csPCa in MRI-TRUS fusion prostate biopsies in men with PI-RADS ≥ 3 lesions, especially for the patients with PI-RADS 3 lesions who gained the most value.
This study is to identify potential multiomics biomarkers for the early detection of the prognostic recurrence of PC patients. A total of 494 prostate adenocarcinoma (PRAD) patients (60-recurrent ...included) from the Cancer Genome Atlas (TCGA) portal were analyzed using the autoencoder model and similarity network fusion. Then, multiomics panels were constructed according to the intersected omics biomarkers identified from the two models. Six intersected omics biomarkers, TELO2, ZMYND19, miR-143, miR-378a, cg00687383 (MED4), and cg02318866 (JMJD6; METTL23), were collected for multiomics panel construction. The difference between the Kaplan–Meier curves of high and low recurrence-risk groups generated from the multiomics panel achieved p-value = 5.33 × 10−9, which is better than the former study (p-value = 5 × 10−7). Additionally, when evaluating the selected multiomics biomarkers with clinical information (Gleason score, age, and cancer stage), a high-performance prediction model was generated with C-index = 0.713, p-value = 2.97 × 10−15, and AUC = 0.789. The risk score generated from the selected multiomics biomarkers worked as an effective indicator for the prediction of PRAD recurrence. This study helps us to understand the etiology and pathways of PRAD and further benefits both patients and physicians with potential prognostic biomarkers when making clinical decisions after surgical treatment.
We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we ...demonstrate how COL11A1 regulates twist family basic helix‐loop‐helix transcription factor 1‐related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA‐mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression‐free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5‐year overall‐survival (p = 0.004) and progression‐free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1‐induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) gene occurred via increased SP1 phosphorylation and binding to the IKKβ promoter. COL11A1‐mediated nuclear factor‐kappa B activation, via transcriptional activation of IKKβ, promoted TWIST1, Mcl‐1, and GAS6 expression, which were associated with chemoresistance and anti‐apoptosis in ovarian cancer cells. We suggest that IKKβ and TWIST1 can potentially be targeted in patients with COL11A1‐positive ovarian cancer.
What's new?
COL11A1 and TWIST1 were previously found to be among the most differentially upregulated genes in chemoresistant ovarian tumors. Here, the authors examined the role of COL11A1‐dependent TWIST1 expression in chemoresistance and clinical outcome of epithelial ovarian carcinoma (EOC). TWIST1 upregulation caused by COL11A1‐induced IKKβ transcription occurred via increased SP1 binding to the IKKβ promoter. COL11A1‐mediated NF‐κB activation, via IKKβ transcriptional activation, promoted TWIST1 and Mcl‐1 or GAS6 expression, which were associated with chemoresistance and apoptosis inhibition. EOC patients with TWIST1 overexpression had higher chemotherapy resistance and shorter survival, highlighting TWIST1 as an important chemoresistance and poor prognosis marker in EOC.
Glucoregulatory efficiency and ATP production are key regulators for neuronal plasticity and memory formation. Besides its chemotactic and neuroinflammatory functions, the CC chemokine--CCL5 displays ...neurotrophic activity. We found impaired learning-memory and cognition in CCL5-knockout mice at 4 months of age correlated with reduced hippocampal long-term potentiation and impaired synapse structure. Re-expressing CCL5 in knockout mouse hippocampus restored synaptic protein expression, neuronal connectivity and cognitive function. Using metabolomics coupled with FDG-PET imaging and seahorse analysis, we found that CCL5 participates in hippocampal fructose and mannose degradation, glycolysis, gluconeogenesis as well as glutamate and purine metabolism. CCL5 additionally supports mitochondrial structural integrity, purine synthesis, ATP generation, and subsequent aerobic glucose metabolism. Overexpressing CCL5 in WT mice also enhanced memory-cognition performance as well as hippocampal neuronal activity and connectivity through promotion of de novo purine and glutamate metabolism. Thus, CCL5 actions on glucose aerobic metabolism are critical for mitochondrial function which contribute to hippocampal spine and synapse formation, improving learning and memory.
Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and ...migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-β3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-β3 antibody. Human tumors with high TGF-β3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-β3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.
Two new 2,3‐dicyanopyrazinophenanthrene‐based acceptors (A) p‐QCN and m‐QCN were synthesized to blend with a donor (D) CPTBF for the exciplex formation. The energy levels of p‐QCN and m‐QCN are ...modulated by the peripheral substituents 4‐ and 3‐benzonitrile, respectively. Exciplex‐forming blends were identified by the observation of the red‐shifted emissions from various D : A blends with higher ratios of donor for suppressing the aggregation of acceptor. The two‐component relaxation processes observed by time‐resolved photoluminescence support the thermally activated delayed fluorescence (TADF) character of the exciplex‐forming blends. The device employing CPTBF : p‐QCN and (2 : 1) and CPTBF : m‐QCN (2 : 1) blend as the emitting layer (EML) gave EQEmax of 1.76 % and 5.12 %, and electroluminescence (EL) λmax of 629 nm and 618 nm, respectively. The device efficiency can be further improved to 4.32 % and 5.57 % with CPTBF : p‐QCN and (4 : 1) and CPTBF : m‐QCN (4 : 1) as the EML, which is consistent with their improved photoluminescence quantum yields (PLQYs). A new fluorescent emitter BPBBT with photoluminescence (PL) λmax of 726 nm and a high PLQY of 67 % was synthesized and utilized as the dopant of CPTBF : m‐QCN (4 : 1) cohost system. The device employing CPTBF : m‐QCN (4 : 1): 5 wt.% BPBBT as the EML gave an EQEmax of 5.02 % and EL λmax centered at 735 nm, however, the weak residual exciplex emission remains. By reducing the donor ratio, the exciplex emission can be completely transferred to BPBBT and the corresponding device with CPTBF : m‐QCN (2 : 1): 5 wt.% BPBBT as the EML can achieve EL λmax of 743 nm and EQEmax of 4.79 %. This work manifests the high efficiency near infrared (NIR) OLED can be realized by triplet excitons harvesting of exciplex‐forming cohost system, followed by the effective energy transfer to an NIR fluorescent dopant.
A yellow‐orange emission exciplex‐forming blend composed of a 2,3 dicyanopyrazinophenanthrene‐based acceptor and a carbazole‐based donor is employed as a thermally activated delayed fluorescence (TADF) cohost system for a donor‐acceptor‐donor‐configured organic near‐infrared emitter to achieve an organic light‐emitting device with electroluminescence centered at 743 nm and a maximum external quantum efficiency of 4.79 % by virtue of the effective energy transfer mechanism.
Organic–inorganic lead halide perovskite solar cells are considered as one of the most promising technologies for future photovoltaics because they show high power conversion efficiency (PCE) and can ...be fabricated through a simple solution process. Non-toxic alkaline-earth metal cations are suitable candidates to replace toxic lead in perovskite because they maintain the charge balance in perovskite and some of them meet the tolerance factor of Goldschmidt's rule. We investigated four kinds of alkaline-earth metal cations (Mg
2+
, Ca
2+
, Sr
2+
, and Ba
2+
) to replace lead cations partially. Among these four alkaline-earth metals, the Ba
2+
is most suitable for Pb
2+
replacement in perovskite films and exhibits the best power conversion efficiency. Furthermore, we systematically studied the crystal structure, absorption behavior and surface morphology of Ba
2+
-doped perovskite films with different doping levels. The relationship between the charge carrier dynamics and Ba
2+
concentration was evaluated by the time-resolved photoluminescence (TRPL) technique. The Ba
2+
-doped perovskite films that can be processed in the environment containing moisture (1.0% relative humidity) are stable. At the optimal 3.0 mol% Ba
2+
replacement, the PCE of the fabricated solar cell is increased from 11.8 to 14.0%, and the PCE of champion devices is as high as 14.9% with increased storage stability.
Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is ...essential to monitor patients' immune status for detecting a rejection/graft failure early on.
We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (
) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation.
in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server.
Datasets covering VDJ regions of
indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients.
Clonal diversity in
-
3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of
iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.
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