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.
Highly reactive copper‐dihydride clusters, Cu15(H)2(S2CNR2)6(C2Ph)6(PF6) {R = nBu (1H), nPr (2H), iBu (3H)}, are isolated during the reaction of Cu28H15{S2CNnBu2}12(PF6) with ten equivalents of ...phenylacetylene. They are found to be intermediates in the formation of the earlier reported two‐electron superatom Cu13(S2CNR2)6(C2Ph)4+. Better yields are obtained by reacting dithiocarbamate sodium salts, Cu(CH3CN)4(PF6), BH4− and phenylacetylene. The presence of two hydrides in the isolated clusters is confirmed by the synthesis and characterization of its deuteride analogue Cu15(D)2(S2CNR2)6(C2Ph)6+, and a single‐crystal neutron structure of 2H. Structural characterization of 1H reveals a new bicapped icosahedral copper(I) cage encapsulating a linear copper dihydride (CuH2)− unit. Reaction of 3H with Au(I) salts yields a highly luminescent AuCu12(S2CNiBu2)6(C2Ph)4+ cluster.
A 15‐nuclear copper dihydride cluster Cu15(H)2(S2CNR2)6(C2Ph)6(PF6) (1) containing a linear CuH2− complex embedded in a Cu1414+ cage is isolated and structurally characterized. This cluster readily converts to a two‐electron superatom cluster Cu1311+ at elevated temperatures. Highly luminescent AuCu12(S2CNR2)6(C2Ph)4+ cluster is isolated by reacting 1 with Au(I) salts.
In sharp contrast to surface hydrides, reactivities of interstitial hydrides are difficult to explore. When treated with a metal ion (Cu+, Ag+, and Au+), the stable CuI dihydride template ...Cu11H2{S2P(OiPr)2}6(C≡CPh)3 (H2Cu11) generates surprisingly three very different compounds, namely CuH2Cu11{S2P(OiPr)2}6(C≡CPh)3+ (1), AgH2Cu14{S2P(OiPr)2}6((C≡CPh)6+ (2), and AuCu11{S2P(OiPr)2}6(C≡CPh)3Cl (3). Compounds 1 and 2 are both MI species and maintain the same number of hydride ligands as their H2Cu11 precursor. Neutron diffraction revealed the first time a trigonal‐pyramidal hydride coordination mode in the AgCu3 environment of 2. 3 has no hydride and exhibits a mixed‐valent AuCu1110+ metal core, making it a two‐electron superatom.
While the reaction of the Cu11H2{S2P(OiPr)2}6(C≡CPh)3 template with Cu+ or Ag+ produces Cu12H2 and AgCu14H2 species in which the hydrides behave as Lewis bases, in the reaction with Au+, the hydrides act as reducing agents, leading to a luminescent, two‐electron Au@Cu11 superatom, whose metal core has a defect fcc structure.
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.
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.
Although atomically precise polyhydrido copper nanoclusters are of prime interest for a variety of applications, they have so far remained scarce. Herein, this work describes the synthesis of a ...dithiophosphate‐protected copper(I) hydride‐rich nanocluster (NC), Cu30H18{S2P(OnPr)2}12 (1H), fully characterized by various spectroscopic methods and single‐crystal X‐ray diffraction. The X‐ray structure of 1H reveals an unprecedented central Cu12 hollow icosahedron. Six faces of this icosahedron are capped by Cu3 triangles, the whole Cu30 core being wrapped by twelve dithiophosphate ligands and the whole cluster has ideal S6 symmetry. The locations of the 18 hydrides in 1H were ascertained by a single‐crystal neutron diffraction study. They are composed of three types: capping μ3‐H, interstitial μ4‐H (seesaw) and μ5‐H ligands (square pyramidal), in good agreement with the DFT simulations. The numbers of hydrides and ligand resonances in the 1H NMR spectrum of 1H are in line with their coordination environment in the solid state, retaining the S6 symmetry in solution. Furthermore, two new Se‐protected polyhydrido copper nanoclusters, Cu30H18{Se2P(OR)2}12 (2H: R=iPr 3H: R=iBu) were synthesized from their sulfur relative 1H via ligand displacement reaction and their X‐ray structures feature the exceptional case where both the NC shape and size are fully conserved during the course of ligand exchange. DFT and TD‐DFT calculations allow understanding the bonding and optical properties of clusters 1H–3H. In addition, the reaction of 1H with Pd(PPh3)2Cl2 in the presence of terminal alkynes led to the formation of new bimetallic Cu−Pd alloy clusters PdCu14H2{S2P(OnPr)2}6(C≡CR)6 (4: R=Ph; 5: R=C6H4F).
An atomically and structurally precise polyhydrido copper nanocluster Cu30H18{S2P(OnPr)2}12 which embodied an unprecedented inner hollow Cu12 icosahedron core has been isolated and fully characterized by single‐crystal neutron diffraction analysis; while existence of Ag12 and Au12 icosahedra have reported in the year 2013 and 2019, respectively.
A structurally precise hydride‐containing Pt‐doped Cu‐rich nanocluster PtH2Cu14{S2P(OiPr)2}6(CCPh)6 (1) has been synthesized. It consists of a bicapped icosahedral Cu14 cage that encapsulates a ...linear PtH2 unit. Upon the addition of two equivalents of CF3COOH to 1, two hydrido clusters are isolated. These clusters are PtHCu11{S2P(OiPr)2}6(CCPh)4 (2), which is a vertex‐missing Cu11 cuboctahedron encaging a PtH moiety, and PtH2Cu11{S2P(OiPr)2}6(CCPh)3 (3), a distorted 3,3,4,4,4‐pentacapped trigonal prismatic Cu11 cage enclosing a PtH2 unit. The electronic structure of 2, analyzed by Density Functional Theory, is a 2e superatom. The electrocatalytic activities of 1–3 for hydrogen evolution reaction (HER) were compared. Notably, Cluster 2 exhibited an exceptionally excellent HER activity within metal nanoclusters, with an onset potential of −0.03 V (at 10 mA cm−2), a Tafel slope of 39 mV dec−1, and consistent HER activity throughout 3000 cycles in 0.5 M H2SO4. Our study suggests that the accessible central Pt site plays a crucial role in the remarkable HER activity and may provide valuable insights for establishing correlations between catalyst structure and HER activity.
To optimize the HER performance, the size, composition, and structure of bimetallic PtH−Cu NCs are controlled with atomic precision. The addition of CF3COOH to cluster 1 resulted in the structural change from a bicapped icosahedral Cu14 cage encapsulating a linear PtH2 unit (HER‐inactive cluster) to a vertex‐missing Cu11 cuboctahedron encaging a PtH moiety in cluster 2 (HER‐active cluster) and distorted 3,3,4,4,4‐pentacapped trigonal prismatic Cu11 cage enclosing a PtH2 unit in cluster 3. Cluster 2 reveals the highest HER activity among the bimetallic NC catalysts with a near‐zero onset potential (η) of −0.03 V (at 10 mA cm−2).
Osteoporosis is a disease that reduces bone mass and microarchitecture, which makes bones fragile. Postmenopausal osteoporosis occurs due to estrogen deficiency. Raloxifene is a selective estrogen ...receptor modulator used to treat postmenopausal osteoporosis. However, it has a low bioavailability, which requires long-term, high-dose raloxifene administration to be effective and causes several side effects. Herein, raloxifene was encapsulated in human serum albumin (HSA)-based nanoparticles (Ral/HSA/PSS NPs) as an intravenous-injection pharmaceutical formulation to increase its bioavailability and reduce the treatment dosage and time. In vitro results indicated that raloxifene molecules were well distributed in HSA-based nanoparticles as an amorphous state, and the resulting raloxifene formulation was stabile during long-term storage duration. The Ral/HSA/PSS NPs were both biocompatible and hemocompatible with a decreased cytotoxicity of high-dose raloxifene. Moreover, the intravenous administration of the prepared Ral/HSA/PSS NPs to rats improved raloxifene bioavailability and improved its half-life in plasma. These raloxifene-loaded nanoparticles may be a potential nanomedicine candidate for treating postmenopausal osteoporosis with lower raloxifene dosages.
The structurally precise Cu‐rich hydride nanoclusters PdCu14H2(dtc/dtp)6(C≡CPh)6 (dtc: di‐butyldithiocarbamate (1); dtp: di‐isopropyl dithiophosphate (2)) were synthesized from the reaction of ...polyhydrido copper clusters Cu28H15(S2CNnBu2)12+ or Cu20H11{S2P(OiPr)2}9 with phenyl acetylene in the presence of Pd(PPh3)2Cl2. Their structures and compositions were determined by single‐crystal X‐ray diffraction and the results supported by ESI‐mass spectrometry. Hydride positions in 1 were confirmed by single‐crystal neutron diffraction. Each hydride is connected to one Pd0 and four CuI atoms in slightly distorted trigonalbipyramidal geometry. The anatomies of clusters 1 and 2 are very similar and DFT calculations allow rationalizing the interactions between the encapsulated PdH22− unit and its Cu14 bicapped icosahedral cage. As a result, Pd has the highest coordination number (14) so far recorded.
Come in number 14: A unique methodology was used to synthesize atomically precise palladium‐alloyed copper hydride clusters. X‐ray and neutron diffraction revealed that a 14‐electron PdH22− unit is iono‐covalently encapsulated within a bicapped icosahedral Cu1414+ cage and, as a result, the central Pd0 adopts the coordination number of 14.
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