Widespread and Functional RNA Circularization in Localized Prostate Cancer.

The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ∼90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.

Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19.

The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching mechanism underlying both initiation and progression of aggressive PCa.

Systematic pan-cancer analysis insights into ICAM1 as an immunological and prognostic biomarker.

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.

Design of Atomically Dispersed CoN4 Sites and Co Clusters for Synergistically Enhanced Oxygen Reduction Electrocatalysis.

Constructing dual-site catalysts consisting of atomically dispersed metal single atoms and metal atomic clusters (MACs) is a promising approach to further boost the catalytic activity for oxygen reduction reaction (ORR). Herein, a porous CoSA-AC@SNC featuring the coexistence of Co single-atom sites (CoN4) and S-coordinated Co atomic clusters (SCo6) in S, N co-doped carbon substrate is successfully synthesized by using porphyrinic metal-organic framework (Co-TPyP MOF) as the precursor. The introduction of the sulfur source creates abundant microstructural defects to anchor Co metal clusters, thus modulating the electronic structure of its surrounding carbon substrate. The synergistic effect between the two types of active sites and structural advantages, in turn, results in high ORR performance of CoSA-AC@SNC with half-wave potential (E1/2) of 0.86 V and Tafel slope of 50.17 mV dec-1. Density functional theory (DFT) calculations also support the synergistic effect between CoN4 and SCo6 by detailing the catalytic mechanism for the improved ORR performance. The as-fabricated Zn-air battery (ZAB) using CoSA-AC@SNC demonstrates impressive peak power density of 174.1 mW cm-2 and charge/discharge durability for 148 h. This work provides a facile synthesis route for dual-site catalysts and can be extended to the development of other efficient atomically dispersed metal-based electrocatalysts.

High-Density CoSe2 Sites Embedded within 2D Porous N-Doped Carbon for High-Performance Oxygen Reduction Reaction Electrocatalysis.

Designing and fabricating efficient and stable nonprecious metal-based oxygen reduction reaction (ORR) electrocatalysts is a pressing and challenging task for the pursuit of sustainable new energy devices. Herein, porous P-CoSe2@NC electrocatalysts with high-density carbon-coated CoSe2 sites were successfully fabricated based on a pyridyl-porphyrinic metal-organic framework (Co-TPyP MOF) via a molten salt-assisted synthesis method. The hierarchical pore and N-doping carbon substrate of P-CoSe2@NC promotes mass transfer and electron-transfer efficiency, which is beneficial to maximize CoSe2 site utilization. Well-designed P-CoSe2@NC exhibits efficient ORR catalytic activity with a high half-wave potential of 0.863 V and excellent catalytic stability. Meanwhile, rechargeable aqueous primary/quasi-solid-state ZABs based on a P-CoSe2@NC air cathode show a high peak power density and exceptional operating stability, catering to the demands of practical applications. The qualified performance and structure stability of the electrocatalytic system may be mainly attributed to the protection of the CoSe2 nanoparticle by the coated carbon layer. Given the rational design of the structure and the component of the electrocatalyst with enhanced ORR activity, we believe that this work has provided a reliable pathway to the development of high-performance transition-metal chalcogenides for energy-storage and -conversion devices.

NiCoP cocatalyst modified g-C3N4 as ohmic junction photocatalyst for efficient degradation of tetracycline under visible light.

Increasing the electron-hole recombination rate in g-C3N4 can effectively improve its photocatalytic performance. In this work, NiCoP/g-C3N4 (NCP/PCN) composites with ohmic junction were formed by embedding granular NiCoP in irregularly porous g-C3N4. There was almost no barrier between the metal and the semiconductor in ohmic junction, which made it easier for electrons to slip from PCN to NCP along the curved energy band, and NCP acted as an electron collector to rapidly capture the slipping electrons. In addition, porous g-C3N4 prepared by supramolecular self-assembly could provide a shorter diffusion path for electrons. Thus, the electron-hole was effectively separated and the photocatalytic performance was improved. The band electronic structure and existence of ohmic junction in 7-NCP/PCN composite were demonstrated by XPS, ESR and DFT calculation. Finally, a reasonable photocatalytic degradation mechanism and possible tetracycline degradation path were proposed. This work has significant potential for providing an effective method for the design of non-precious metal photocatalysts.

Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

Evaluating the performance and influencing factors of three portable black carbon monitors for field measurement.

Black carbon (BC) is associated with adverse human health and climate change. Mapping BC spatial distribution imperatively requires low-cost and portable devices. Several portable BC monitors are commercially available, but their accuracy and reliability are not always satisfactory during continuous field observation. This study evaluated three models of portable black carbon monitors, C12, MA350 and DST, and investigates the factors that affect their performance. The monitors were tested in urban Beijing, where portable devices running for one month alongside a regular-size reference aethalometer AE33. The study considers several factors that could influence the monitors' performance, including ambient weather, aerosol composition, loading artifacts, and built-in algorithms. The results show that MA350 and DST present considerable discrepancies to the reference instrument, mainly occurring at lower concentrations (0-500 ng/m3) and higher concentrations (2500-8000 ng/m3), respectively. These discrepancies were likely caused by the anomalous noise of MA350 and the loading artifacts of DST. The study also suggests that the ambient environment has limited influence on the monitors' performance, but loading artifacts and accompanying compensation algorithms can result in unrealistic data. Based on the evaluation, the study suggests that C12 is the best choice for unsupervised field measurement, DST should be used in scenarios where frequent maintenance is available, and MA350 is suitable for research purposes with post-processing applicable. The study highlights the importance of assigning portable BC monitors to appropriate applications and the need for optimized real-time compensation algorithms.

Device-Independent Quantum Key Distribution Based on the Mermin-Peres Magic Square Game.

Device-independent quantum key distribution (DIQKD) is information-theoretically secure against adversaries who possess a scalable quantum computer and who have supplied malicious key-establishment systems; however, the DIQKD key rate is currently too low. Consequently, we devise a DIQKD scheme based on the quantum nonlocal Mermin-Peres magic square game: our scheme asymptotically delivers DIQKD against collective attacks, even with noise. Our scheme outperforms DIQKD using the Clauser-Horne-Shimony-Holt game with respect to the number of game rounds, albeit not number of entangled pairs, provided that both state visibility and detection efficiency are high enough.

Low-rank latent matrix-factor prediction modeling for generalized high-dimensional matrix-variate regression.

Motivated by diagnosing the COVID-19 disease using two-dimensional (2D) image biomarkers from computed tomography (CT) scans, we propose a novel latent matrix-factor regression model to predict responses that may come from an exponential distribution family, where covariates include high-dimensional matrix-variate biomarkers. A latent generalized matrix regression (LaGMaR) is formulated, where the latent predictor is a low-dimensional matrix factor score extracted from the low-rank signal of the matrix variate through a cutting-edge matrix factor model. Unlike the general spirit of penalizing vectorization plus the necessity of tuning parameters in the literature, instead, our prediction modeling in LaGMaR conducts dimension reduction that respects the geometric characteristic of intrinsic 2D structure of the matrix covariate and thus avoids iteration. This greatly relieves the computation burden, and meanwhile maintains structural information so that the latent matrix factor feature can perfectly replace the intractable matrix-variate owing to high-dimensionality. The estimation procedure of LaGMaR is subtly derived by transforming the bilinear form matrix factor model onto a high-dimensional vector factor model, so that the method of principle components can be applied. We establish bilinear-form consistency of the estimated matrix coefficient of the latent predictor and consistency of prediction. The proposed approach can be implemented conveniently. Through simulation experiments, the prediction capability of LaGMaR is shown to outperform some existing penalized methods under diverse scenarios of generalized matrix regressions. Through the application to a real COVID-19 dataset, the proposed approach is shown to predict efficiently the COVID-19.

Describing proton transfer modes in shared proton systems with constrained nuclear-electronic orbital methods.

Proton transfer is crucial in various chemical and biological processes. Because of significant nuclear quantum effects, accurate and efficient description of proton transfer remains a great challenge. In this Communication, we apply constrained nuclear-electronic orbital density functional theory (CNEO-DFT) and constrained nuclear-electronic orbital molecular dynamics (CNEO-MD) to three prototypical shared proton systems and investigate their proton transfer modes. We find that with a good description of nuclear quantum effects, CNEO-DFT and CNEO-MD can well describe the geometries and vibrational spectra of the shared proton systems. Such a good performance is in significant contrast to DFT and DFT-based ab initio molecular dynamics, which often fail for shared proton systems. As an efficient method based on classical simulations, CNEO-MD is promising for future investigations of larger and more complex proton transfer systems.

Synthesis of High Specific Surface Lithium-Ion Sieve Templated by Bacterial Cellulose for Selective Adsorption of Li.

In recent years, with the development of batteries, ceramics, glass and other industries, the demand for lithium has increased rapidly. Due to the rich lithium resources in seawater and salt-lake brine, the question of how to selectively adsorb and separate lithium ions from such brine has attracted the attention and research of many scholars. The Li-ion sieve stands out from other methods thanks to its excellent special adsorption and separation performance. In this paper, mesoporous titanium dioxide and lithium hydroxide were prepared by hydrothermal reaction using bacterial cellulose as a biological template. After calcination at 600 °C, spinel lithium titanium oxide Li2TiO3 was formed. The precursor was eluted with HCl eluent to obtain H2TiO3. The lithium titanate were characterized by IR, SEM and X-ray diffraction. The adsorption properties of H2TiO3 were studied by adsorption pH, adsorption kinetics, adsorption isotherm and competitive adsorption. The results show that H2TiO3 has a single-layer chemical adsorption process, and has a good adsorption effect on lithium ions at pH 11.0, with a maximum adsorption capacity of 35.45 mg g-1. The lithium-ion sieve can selectively adsorb Li+, and its partition coefficient is 2242.548 mL g-1. It can be predicted that the lithium-ion sieve prepared by biological template will have broad application prospects.

Stabilizing Liquids Using Interfacial Supramolecular Assemblies.

Stabilizing liquids based on supramolecular assembly (non-covalent intermolecular interactions) has attracted significant interest, due to the increasing demand for soft, liquid-based devices where the shape of the liquid is far from the equilibrium spherical shape. The components comprising these interfacial assemblies must have sufficient binding energies to the interface to prevent their ejection from the interface when the assemblies are compressed. Here, we highlight recent advances in structuring liquids based on non-covalent intermolecular interactions. We describe some of the progress made that reveals structure-property relationships. In addition to treating advances, we discuss some of the limitations and provide a perspective on future directions to inspire further studies on structured liquids based on supramolecular assembly.

Device-Independent Quantum Key Distribution with Random Postselection.

Device-independent quantum key distribution (QKD) can permit the superior security even with unknown devices. In practice, however, the realization of device-independent QKD is technically challenging because of its low noise tolerance. In the photonic setup, due to the limited detection efficiency, a large amount of the data generates from no-detection events which contain few correlations but contribute high errors. Here, we propose the device-independent QKD protocol with random postselection, where the secret keys are extracted only from the postselected subset of outcomes. This could not open the detection loophole as long as the entropy of the postselected subset is evaluated from the information of the entire set of data, including both detection and no-detection events. This postselection has the advantage to significantly reduce the error events, thus relaxing the threshold of required detection efficiency. In the model of collective attacks, our protocol can tolerate detector efficiency as low as 68.5%, which goes beyond standard security proofs. The results make a concrete step for the implementation of device-independent QKD in practice.

Toward a Photonic Demonstration of Device-Independent Quantum Key Distribution.

The security of quantum key distribution (QKD) usually relies on that the users' devices are well characterized according to the security models made in the security proofs. In contrast, device-independent QKD-an entanglement-based protocol-permits the security even without any knowledge of the underlying quantum devices. Despite its beauty in theory, device-independent QKD is elusive to realize with current technologies. Especially in photonic implementations, the requirements for detection efficiency are far beyond the performance of any reported device-independent experiments. In this Letter, we report a proof-of-principle experiment of device-independent QKD based on a photonic setup in the asymptotic limit. On the theoretical side, we enhance the loss tolerance for real device imperfections by combining different approaches, namely, random postselection, noisy preprocessing, and developed numerical methods to estimate the key rate via the von Neumann entropy. On the experimental side, we develop a high-quality polarization-entangled photon source achieving a state-of-the-art (heralded) detection efficiency about 87.5%. Although our experiment does not include random basis switching, the achieved efficiency outperforms previous photonic experiments involving loophole-free Bell tests. Together, we show that the measured quantum correlations are strong enough to ensure a positive key rate under the fiber length up to 220 m. Our photonic platform can generate entangled photons at a high rate and in the telecom wavelength, which is desirable for high-speed generation over long distances. The results present an important step toward a full demonstration of photonic device-independent QKD.

Measurement-Device-Independent Verification of a Quantum Memory.

In this Letter we report an experiment that verifies an atomic-ensemble quantum memory via a measurement-device-independent scheme. A single photon generated via Rydberg blockade in one atomic ensemble is stored in another atomic ensemble via electromagnetically induced transparency. After storage for a long duration, this photon is retrieved and interfered with a second photon to perform a joint Bell-state measurement (BSM). The quantum state for each photon is chosen based on a quantum random number generator, respectively, in each run. By evaluating correlations between the random states and BSM results, we certify that our memory is genuinely entanglement preserving.

Remote Blind State Preparation with Weak Coherent Pulses in the Field.

Quantum computing has seen tremendous progress in past years. Due to implementation complexity and cost, the future path of quantum computation is strongly believed to delegate computational tasks to powerful quantum servers on the cloud. Universal blind quantum computing (UBQC) provides the protocol for the secure delegation of arbitrary quantum computations, and it has received significant attention. However, a great challenge in UBQC is how to transmit a quantum state over a long distance securely and reliably. Here, we solve this challenge by proposing a resource-efficient remote blind qubit preparation (RBQP) protocol, with weak coherent pulses for the client to produce, using a compact and low-cost laser. We experimentally verify a key step of RBQP-quantum nondemolition measurement-in the field test over 100 km of fiber. Our experiment uses a quantum teleportation setup in the telecom wavelength and generates 1000 secure qubits with an average fidelity of (86.9±1.5)%, which exceeds the quantum no-cloning fidelity of equatorial qubit states. The results prove the feasibility of UBQC over long distances, and thus serves as a key milestone towards secure cloud quantum computing.

Influence of gender and age on the Dysphonia Severity Index: A normative study in a Shanghainese population.

Dysphonia Severity Index (DSI) is an objective multi-parametric measurement of voice quality, which has been widely used in different countries. Studies indicate that DSI may be influenced by vocal pathology, age and geographical factors, whereas gender does not significantly affect DSI. The purpose of this study was to investigate the effects of gender and age on the DSI and related parameters in a Shanghainese population. The present study measured the DSI and the parameters maximum phonation time (MPT), highest fundamental frequency (HF0), lowest intensity (LI) and Jitter in 187 Shanghainese subjects, including 106 young adults aged 18-23 years (52 males and 54 females) and 81 children aged 7-9 years (44 boys and 37 girls). Two-way analysis of variance indicated that HF0 was significantly higher in female subjects than in male subjects, in both young adults and children. Gender was not significantly associated with MPT, LI, jitter or DSI. With regard to age, MPT and DSI were significantly higher in young adults than in children, and HF0 and LI were significantly lower. No significant associations between age and jitter were detected. In terms of clinic significance, the results of this study may contribute to the establishment of a normal reference range for Shanghainese DSI values, and the influence of gender and age on DSI and its separate components.

Peptide recognition by heterochromatin protein 1 (HP1) chromoshadow domains revisited: Plasticity in the pseudosymmetric histone binding site of human HP1.

Heterochromatin protein 1 (HP1), a highly conserved non-histone chromosomal protein in eukaryotes, plays important roles in the regulation of gene transcription. Each of the three human homologs of HP1 includes a chromoshadow domain (CSD). The CSD interacts with various proteins bearing the PXVXL motif but also with a region of histone H3 that bears the similar PXXVXL motif. The latter interaction has not yet been resolved in atomic detail. Here we demonstrate that the CSDs of all three human HP1 homologs have comparable affinities to the PXXVXL motif of histone H3. The HP1 C-terminal extension enhances the affinity, as does the increasing length of the H3 peptide. The crystal structure of the human HP1γ CSD (CSDγ) in complex with an H3 peptide suggests that recognition of H3 by CSDγ to some extent resembles CSD-PXVXL interaction. Nevertheless, the prolyl residue of the PXXVXL motif appears to play a role distinct from that of Pro in the known HP1ß CSD-PXVXL complexes. We consequently generalize the historical CSD-PXVXL interaction model and expand the search scope for additional CSD binding partners.

Crystal structure of the WD40 domain of human PRPF19.

Human Pre-mRNA Processing factor 19 (hPRPF19) is an important component in human spliceosome machinery. hPRPF19 contains a WD40 repeats domain at its C-terminus, which is also conserved in yeast. Here we determined the crystal structure of the C-terminal WD40 repeat domain of hPRPF19 by X-ray crystallography. Our structural analysis revealed some significantly different structure features between the human and yeast Prp19 WD40 repeat domain. However, there are also conserved clusters of residues at the bottom surface of the fourth and the fifth WD40 repeats, which provides the important implication for the conserved Prp19 proteins in both human and yeast.