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Abstract Background Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored. Methods The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches. Results Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3’-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects. Conclusions Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy.

Abstract Organic scintillators have recently gained considerable attentions in X‐ray detection for their potential applications in biomedical radiograph and security inspection. However, the weak X‐ray absorption and/or inefficient exciton utilization have limited the development and commercialization of organic scintillators. Currently, high‐performance X‐ray organic scintillators are scarce and organic scintillators with dual triplet‐harvesting channels have not been explored before. Here, we develop several proof‐of‐concept sulfone‐based organic molecules, C1–C7, using different alkoxy chains to manipulate molecular packing mode. These materials exhibit dual triplet‐harvesting channels of thermally activated delayed fluorescence (TADF) and room‐temperature phosphorescence (RTP) in aggregated state. Inspiringly, these molecules display distinct radioluminescence under the X‐ray stimulation. Among them, C6 behaves the highest light yield of 16,558 photons MeV−1. Moreover, clear X‐ray images are demonstrated in both aggregated state and single‐molecule level. High spatial resolutions of 15.0 and 10.6 line pairs per millimeter (lp mm−1) are achieved for rigid and flexible scintillator screens, exceeding most reported organic and conventional inorganic scintillators. These results highlight the great potential of organic molecules with TADF and RTP nature for efficient X‐ray scintillation and imaging.

Abstract Background Phosphatase and tensin homolog deleted on chromosome ten (PTEN) serves as a powerful tumor suppressor, and has been found to be downregulated in human bladder cancer (BC) tissues. Despite this observation, the mechanisms contributing to PTEN’s downregulation have remained elusive. Methods We established targeted genes’ knockdown or overexpressed cell lines to explore the mechanism how it drove the malignant transformation of urothelial cells or promoted anchorageindependent growth of human basal muscle invasive BC (BMIBC) cells. The mice model was used to validate the conclusion in vivo. The important findings were also extended to human studies. Results In this study, we discovered that mice exposed to N-butyl-N-(4-hydroxybu-tyl)nitrosamine (BBN), a specific bladder chemical carcinogen, exhibited primary BMIBC accompanied by a pronounced reduction in PTEN protein expression in vivo. Utilizing a lncRNA deep sequencing high-throughput platform, along with gain- and loss-of-function analyses, we identified small nucleolar RNA host gene 1 (SNHG1) as a critical lncRNA that might drive the formation of primary BMIBCs in BBN-treated mice. Cell culture results further demonstrated that BBN exposure significantly induced SNHG1 in normal human bladder urothelial cell UROtsa. Notably, the ectopic expression of SNHG1 alone was sufficient to induce malignant transformation in human urothelial cells, while SNHG1 knockdown effectively inhibited anchorage-independent growth of human BMIBCs. Our detailed investigation revealed that SNHG1 overexpression led to PTEN protein degradation through its direct interaction with HUR. This interaction reduced HUR binding to ubiquitin-specific peptidase 8 (USP8) mRNA, causing degradation of USP8 mRNA and a subsequent decrease in USP8 protein expression. The downregulation of USP8, in turn, increased PTEN polyubiquitination and degradation, culminating in cell malignant transformation and BMIBC anchorageindependent growth. In vivo studies confirmed the downregulation of PTEN and USP8, as well as their positive correlations in both BBN-treated mouse bladder urothelium and tumor tissues of bladder cancer in nude mice. Conclusions Our findings, for the first time, demonstrate that overexpressed SNHG1 competes with USP8 for binding to HUR. This competition attenuates USP8 mRNA stability and protein expression, leading to PTEN protein degradation, consequently, this process drives urothelial cell malignant transformation and fosters BMIBC growth and primary BMIBC formation.

During reactor operation, the divertor must withstand unprecedented simultaneous high heat fluxes and high-energy neutron irradiation. The extremely severe service environment of the divertor imposes a huge challenge to the bonding quality of divertor joints, i.e., the joints must withstand thermal, mechanical and neutron loads, as well as cyclic mode of operation. In this paper, potassium-doped tungsten (KW) is selected as the plasma facing material (PFM), oxygen-free copper (OFC) as the interlayer, oxide dispersion strengthened copper (ODS-Cu) alloy as the heat sink material, and reduced activation ferritic/martensitic (RAFM) steel as the structural material. In this study, a vacuum brazing technology is proposed and optimized to bond Cu and ODS-Cu alloy with the silver-free brazing material CuSnTi. The most appropriate brazing parameters are a brazing temperature of 940 °C and a holding time of 15 min. High-quality bonding interfaces have been successfully obtained by vacuum brazing technology, and the average shear strength of the as-obtained KW/Cu and ODS-Cu alloy joints is ∼268 MPa. And a fabrication route for manufacturing the flat-type divertor target based on brazing technology is set. For evaluating the reliability of the fabrication technologies under the reactor relevant condition, the high heat flux test at 20 MW/m2 for the as-manufactured flat-type KW/Cu/ODS-Cu/RAFM mockup is carried out by using the Electron-beam Material testing Scenario (EMS-60) with water cooling. This paper reports the improved vacuum brazing technology to connect Cu to ODS-Cu alloy and summarizes the production route, high heat flux (HHF) test, the pre and post non-destructive examination, and the surface results of the flat-type KW/Cu/ODS-Cu/RAFM mockup after the HHF test. The test results demonstrate that the mockup manufactured according to the fabrication route still have structural and interfacial integrity under cyclic high heat loads.

Transfer printing of small-molecular organic semiconductors often faces challenges due to surface adhesion mismatch. Here, we developed a sacrificing-layer-assisted transfer printing technique for the deposition of small-molecular thin films. High-boiling-point ethylene glycol (EG) was doped in aqueous solution poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as the sacrificing layer to manipulate residual water in film, which allowed chlorobenzene solution to spontaneously spread and form uniform film. The residual water guaranteed film delamination from the stamp, allowing for its transfer onto various substrates and seeding layers. As a proof of concept, laterally conductive organic photodetectors using recyclable EG-PEDOT:PSS electrodes and a small-molecular active layer were consecutively fabricated via transfer printing in ambient air. The resulting device exhibited a high on/off ratio of 711 and a fast rise time of 0.5 ms. Notably, the polymer electrode and the bulk heterojunction demonstrated unique repairability and recyclability.

Abstract Ternary chalcogenide, silver antimony sulfide (AgSbS2), has emerged with great potential for optoelectronic applications, thanks to its excellent optical properties, facile processability and superior stability. However, high‐performance AgSbS2‐based photodiodes have not been realized mainly due to the large dark current caused by the poor morphology and device leakage. Here, compact AgSbS2 and porous AgSbS2 thin films are fabricated mainly via modulating the sol–gel processes of the precursors. After optimizing the Ag content and the thermal annealing temperature of the AgSbS2 films, AgSbS2 photodiodes with excellent performance metrics, including low dark current density, decent specific detectivity, and superior stability, are achieved. Furthermore, the optimized AgSbS2‐based photodetectors are also introduced for heart rate detection, which exhibit excellent sensitivity and great potential for real applications.

Here the authors show that Omicron neutralizing antibody titers decline over time in mice immunized with a wild-type (WT) lipid nanoparticle (LNP)-mRNA vaccine and are robustly increased by WT or Omicron LNP-mRNA and that Omicron boosters elicit higher BA.1-neutralizing titer than WT boosters.

Abstract Background Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features. Methods We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|> 0.5) to estimate sample sizes for disease progression (disease duration > 14 years vs. ≤ 14 years). Results Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13–49 years; median disease duration, 14 years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12–27%; thoracic levels 41–60%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n = 22) much less that what would be required if using clinical disability assessment (n = 124). Conclusions SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials. Trial registration ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, https://clinicaltrials.gov/ct2/show/NCT04006418?term=NCT04006418&draw=2&rank=1 .

Abstract Despite extensive study, the bandgap characteristics of lead halide perovskites are not well understood. Usually, these materials are considered as direct bandgap semiconductors, while their photoluminescence quantum yield (PLQY) is very low in the solid state or single crystal (SC) state. Some researchers have noted a weak indirect bandgap below the direct bandgap transition in these perovskites. Herein, application of pressure to a CsPbBr3 SC and first‐principles calculations reveal that the nature of the bandgap becomes more direct at a relatively low pressure due to decreased dynamic Rashba splitting. This effect results in a dramatic PLQY improvement, improved more than 90 times, which overturns the traditional concept that the PLQY of lead halide perovskite SC cannot exceed 10%. Application of higher pressure transformed the CsPbBr3 SC into a pure indirect bandgap phase, which can be maintained at near‐ambient pressure. It is thus proved that lead halide perovskites can induce a phase transition between direct and indirect bandgaps. In addition, distinct piezochromism is observed for a perovskite SC for the first time. This work provides a novel framework to understand the optoelectronic properties of these important materials.

Perovskite single crystals are commonly grown in organic solvents, which require relatively high temperature condition. Here, the authors develop a low-temperature crystallisation strategy to grow CsPbBr3 single crystals in water with improved charge transport properties and stability.

Owing to large exciton binding energy, quasi-2D perovskite is promising for light-emitting application, yet inhomogeneous phases distribution limits the potential. Here, the authors improve the performance by using MeS additive to regulate the phase distribution and to reduce defect density in the films.

BackgroundCue-induced craving is widely considered to be the most important risk factor for relapse during abstinence from methamphetamine (Meth). There is limited research regarding electroencephalography (EEG) microstates of Meth-dependent patients under exposure to drug-related cues. Our objective was to investigate whether EEG microstate temporal characteristics could capture neural correlates of cue-induced Meth craving in virtual reality (VR) environments.MethodsEEG recordings of 35 Meth-dependent patients and 30 healthy controls (HCs) were collected during eyes-open state and cue-induced state, respectively. Group differences and condition differences in temporal parameters of four microstate classes were compared.ResultsThe results demonstrated the greater presence of microstate B in both Meth-dependent patients and HCs during the cue-induced condition, compared to resting state. In addition, for Meth-dependent patients, microstate C occurred significantly less frequently, along with a tendency of increased occurrence for class D during the cue-induced condition, compared to resting state. However, the change direction of class C and class D in HCs was completely opposite to that of Meth-dependent patients. The cue-induced condition also elicited different changes in transition probability between Meth-dependent patients and HCs.ConclusionThis study explored the features of EEG microstates in Meth-dependent patients during the cue-induced condition, which can improve our understanding of Meth addiction and contribute to the development of effective assessments and intervention tools.

Perovskites are appealing for optoelectronics, but high-quality perovskite single crystals should be grown at low temperature to minimize trap density. Here, the authors report a room-temperature liquid-diffused-induced crystallization for growth of high-quality hybrid perovskite single crystals.

The divertor is usually exposed to extreme incident heat flux conditions in nuclear fusion engineering and its ability to remove the heat is extremely crucial for the safe operation of magnetic confinement nuclear fusion device. The evaluation of the heat removal capacity of the divertor has been always based on high heat flux (HHF) tests. Yet such methods are only available for the small size of experimental components, it is more difficult to compare under different loading and cooling conditions. In order to assess the heat removal capacity in real time and accurately, a new method was developed to characterize the heat removal capacity of the divertor and other high heat load components based on the cooling water thermal decay time constant, the time constants model has also been established. The thermal decay time constant was obtained by fitting the characteristic curves of the water temperature differences with time during the cooling phase of different components under HHF tests. This index is used to quantitatively analyze, characterize and evaluate the heat transfer capacity of the system of the divertor.

Using machine learning to predict the intensity of pain from fMRI has attracted rapidly increasing interests. However, due to remarkable inter- and intra-individual variabilities in pain responses, the performance of existing fMRI-based pain prediction models is far from satisfactory. The present study proposed a new approach which can design a prediction model specific to each individual or each experimental trial so that the specific model can achieve more accurate prediction of the intensity of nociceptive pain from single-trial fMRI responses. More precisely, the new approach uses a supervised k-means method on nociceptive-evoked fMRI responses to cluster individuals or trials into a set of subgroups, each of which has similar and consistent fMRI activation patterns. Then, for a new test individual/trial, the proposed approach chooses one subgroup of individuals/trials, which has the closest fMRI patterns to the test individual/trial, as training samples to train an individual-specific or a trial-specific pain prediction model. The new approach was tested on a nociceptive-evoked fMRI dataset and achieved significantly higher prediction accuracy than conventional non-specific models, which used all available training samples to train a model. The generalizability of the proposed approach is further validated by training specific models on one dataset and testing these models on an independent new dataset. This proposed individual-specific and trial-specific pain prediction approach has the potential to be used for the development of individualized and precise pain assessment tools in clinical practice.

The main objective of yoga pose grading is to assess the input yoga pose and compare it to a standard pose in order to provide a quantitative evaluation as a grade. In this paper, a computer vision-based yoga pose grading approach is proposed using contrastive skeleton feature representations. First, the proposed approach extracts human body skeleton keypoints from the input yoga pose image and then feeds their coordinates into a pose feature encoder, which is trained using contrastive triplet examples; finally, a comparison of similar encoded pose features is made. Furthermore, to tackle the inherent challenge of composing contrastive examples in pose feature encoding, this paper proposes a new strategy to use both a coarse triplet example—comprised of an anchor, a positive example from the same category, and a negative example from a different category, and a fine triplet example—comprised of an anchor, a positive example, and a negative example from the same category with different pose qualities. Extensive experiments are conducted using two benchmark datasets to demonstrate the superior performance of the proposed approach.

Optoelectronics: Unipolar electron transport in fullerene diodes Fullerenes are commonly used in organic solar cells to attract and trap negatively charged electrons, whilst being able to block positively charged holes in photodiodes applications. Then the question is whether or not fullerenes conduct only one type of charge carriers, namely being unipolar, or are bipolar depending on the setups. A team led by Paul Meredith at Australia's University of Queensland evaluated the electron and hole transport mobility in neat PC70BM and PC60BM films using metal-insulator-semiconductor diodes, which are sensitive to the intrinsic transport properties of the samples. Their data showed that the hole mobility in bulk fullerenes is orders of magnitude lower than that of electrons and below the limits of their measurement, 10–9 cm2/Vs, indicating fullerenes are predominately unipolar. This research may help us better design fullerene-based optoelectronics and solar cells with high charge injection and extraction capability.

Decoding subjective pain perception from functional magnetic resonance imaging (fMRI) data using machine learning technique is gaining a growing interest. Despite the well-documented individual differences in pain experience and brain responses, it still remains unclear how and to what extent these individual differences affect the performance of between-individual fMRI-based pain prediction. The present study is aimed to examine the relationship between individual differences in pain prediction models and between-individual prediction error, and, further, to identify brain regions that contribute to between-individual prediction error. To this end, we collected and analyzed fMRI data and pain ratings in a laser-evoked pain experiment. By correlating different types of individual difference metrics with between-individual prediction error, we are able to quantify the influence of these individual differences on prediction performance and reveal a set of brain regions whose activities are related to prediction error. Interestingly, we found that the precuneus, which does not have predictive capability to pain, could also affect the prediction error. This study elucidates the influence of interindividual variability in pain on the between-individual prediction performance, and the results will be useful for the design of more accurate and robust fMRI-based pain prediction models.

The level of pain perception is correlated with the magnitude of pain-evoked brain responses, such as laser-evoked potentials (LEP), across trials. The positive LEP-pain relationship lays the foundation for pain prediction based on single-trial LEP, but cross-individual pain prediction does not have a good performance because the LEP-pain relationship exhibits substantial cross-individual difference. In this study, we aim to explain the cross-individual difference in the LEP-pain relationship using inter-stimulus EEG (isEEG) features. The isEEG features (root mean square as magnitude and mean square successive difference as temporal variability) were estimated from isEEG data (at full band and five frequency bands) recorded between painful stimuli. A linear model was fitted to investigate the relationship between pain ratings and LEP response for fast-pain trials on a trial-by-trial basis. Then the correlation between isEEG features and the parameters of LEP-pain model (slope and intercept) was evaluated. We found that the magnitude and temporal variability of isEEG could modulate the parameters of an individual's linear LEP-pain model for fast-pain trials. Based on this, we further developed a new individualized fast-pain prediction scheme, which only used training individuals with similar isEEG features as the test individual to train the fast-pain prediction model, and obtained improved accuracy in cross-individual fast-pain prediction. The findings could help elucidate the neural mechanism of cross-individual difference in pain experience and the proposed fast-pain prediction scheme could be potentially used as a practical and feasible pain prediction method in clinical practice.

Introduction: Current clinical detection of Human immunodeficiency virus 1 (HIV-1) is used to target viral genes and proteins. However, the immunoassay, such as viral culture or Polymerase Chain Reaction (PCR), lacks accuracy in the diagnosis, as these conventional assays rely on the stable genome and HIV-1 is a highly-mutated virus. Next generation sequencing (NGS) promises to be transformative for the practice of infectious disease, and the rapidly reducing cost and processing time mean that this will become a feasible technology in diagnostic and research laboratories in the near future. The technology offers the superior sensitivity to detect the pathogenic viruses, including unknown and unexpected strains. Aim: To leverage the NGS technology in order to improve current HIV-1 diagnosis and genotyping methods. Materials and Methods: Ten blood samples were collected from HIV-1 infected patients which were diagnosed by RT PCR at Singapore Communicable Disease Centre, Tan Tock Seng Hospital from October 2014 to March 2015. Viral RNAs were extracted from blood plasma and reversed into cDNA. The HIV-1 cDNA samples were cleaned up using a PCR purification kit and the sequencing library was prepared and identified through MiSeq. Results: Two common mutations were observed in all ten samples. The common mutations were identified at genome locations 1908 and 2104 as missense and silent mutations respectively, conferring S37N and S3S found on aspartic protease and reverse transcriptase subunits. Conclusion: The common mutations identified in this study were not previously reported, therefore suggesting the potential for them to be used for identification of viral infection, disease transmission and drug resistance. This was especially the case for, missense mutation S37N which could cause an amino acid change in viral proteases thus reducing the binding affinity of some protease inhibitors. Thus, the unique common mutations identified in this study could be used as diagnostic biomarkers to indicate the origin of infection as being from Singapore.

Leukoaraiosis is common in patients with acute ischemic stroke. The results from many studies investigating the association between leukoaraiosis and intracranial hemorrhage after thrombolysis remain conflicting.A meta-analysis was performed to compare the risk of post-thrombolytic intracranial hemorrhage in patients with and without leukoaraiosis. Relevant reports were identified by searching PubMed, EmBase, Cochrane Library, and ISI Web of Science through December 2015 using a combination of subjective and random terms. Eligible studies that were original articles with a clear definition of leukoaraiosis and intracranial hemorrhage were selected and analyzed. Funnel plots, Egger's test, and Begg's test were conducted to assess the publication bias. Sensitivity analysis was also performed to evaluate the influence of each individual study.Eleven trials that enrolled 6912 participants were included. There was a significantly increased risk for acute ischemic stroke patients with leukoaraiosis (odds ratio: 1.89, 95% confidence interval 1.51-2.37, P