An activity-based sensing fluorogenic probe for monitoring O-methyltransferase in plants.

Activity-based sensing probes are powerful tools for monitoring enzymatic activities in complex biological samples such as cellular and live animals; however, their application in plants remains challenging. Herein, fourteen activity-based fluorescent probes were assayed against Arabidopsis O-methyltransferases (AtOMTs). One probe, 3-BTD, displayed a high selectivity, reactivity, and fluorescence response toward AtOMTs especially the isoform AtCCoAOMT. We further characterized the features of this probe and explored whether it could be used to detect OMT activities in living plant cells. Our results show that 3-BTD can be used to visualize OMT activity in Arabidopsis, and no fluorescent signal was observed in the comt/ccoaomt double mutant, indicating that it has good specificity. Interestingly, in contrast to the observation that AtCCoAOMT-YFP accumulated in both cytoplasm and nucleus, OMT enzymatic activity tracked by 3-BTD probe was found only in the cytoplasm. This underscores the importance of activity-based sensing in studying protein function. Moreover, 3-BTD can be successfully applied in OMT visualization of different plants. This study indicates that 3-BTD can serve as a potential probe for in situ monitoring the real activity of OMT in multiple plants and provides a strategy for visualizing the activity of other enzymes in plants.

Baseline Performance of Ultrasound-Based Strategies in Breast Cancer Screening Among Chinese Women.

RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3‰) in the 35-44 years age group and 25 (4.2‰) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.

A Non-Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS/TGF-ß1 Signaling.

Pulmonary hypertension (PH) is a life-threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non-metallic nanozyme is reported for the treatment of monocrotaline (MCT)-induced PH with a therapeutic mechanism involving the ROS/TGF-ß1 signaling. The synthesized melanin-polyvinylpyrrolidone-polyethylene glycol (MPP) nanoparticles showcase ultra-small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT-PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS-driven activation of TGF-ß1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non-metallic nanozymes based on a well-understood mechanism.

Mechanistic insights into lanthipeptide modification by a distinct subclass of LanKC enzyme that forms dimers.

Naturally occurring lanthipeptides, peptides post-translationally modified by various enzymes, hold significant promise as antibiotics. Despite extensive biochemical and structural studies, the events preceding peptide modification remain poorly understood. Here, we identify a distinct subclass of lanthionine synthetase KC (LanKC) enzymes with distinct structural and functional characteristics. We show that PneKC, a member of this subclass, forms a dimer and possesses GTPase activity. Through three cryo-EM structures of PneKC, we illustrate different stages of peptide PneA binding, from initial recognition to full binding. Our structures show the kinase domain complexed with the PneA core peptide and GTPγS, a phosphate-bound lyase domain, and an unconventional cyclase domain. The leader peptide of PneA interact with a gate loop, transitioning from an extended to a helical conformation. We identify a dimerization hot spot and propose a "negative cooperativity" mechanism toggling the enzyme between tense and relaxed conformation. Additionally, we identify an important salt bridge in the cyclase domain, differing from those in in conventional cyclase domains. These residues are highly conserved in the LanKC subclass and are part of two signature motifs. These results unveil potential differences in lanthipeptide modification enzymes assembly and deepen our understanding of allostery in these multifunctional enzymes.

Ultrahigh-Resolution Visualization of Vascular Heterogeneity in Brain Tumors via Magnetic Nanoparticles-Enhanced Susceptibility-Weighted Imaging.

The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.

Gram-Scale Synthesis of Renal-Clearable Tantalum Nanodots with High Water Solubility for Computed Tomography Imaging In Vivo.

Tantalum (Ta) emerges as a promising element for advanced computed tomography (CT) imaging probes owing to its high X-ray attenuation coefficient and excellent biocompatibility. Nevertheless, the synthesis of renally clear Ta-based imaging probes through simple methods remains a significant challenge. Herein, we introduce a simple and gram-scale approach for the synthesis of renal-clearable Ta nanodots with high water solubility for CT imaging in vivo. The Ta nanodots, coordination polymers, are fabricated via coordination reactions involving Ta(OH)5, citric acid (CA), and hydrogen peroxide. The Ta nanodots exhibit an ultrasmall hydrodynamic diameter (2.8 nm), high water solubility (1.88 g/mL, 688 mg Ta/mL), superior X-ray absorption capacity, gram-scale production capability (>10 g in lab synthesis), renal-clearable ability, and good biocompatibility. The Ta nanodots possess superior CT imaging efficacy across diverse tube voltages, enabling highly sensitive gastrointestinal CT imaging, renal CT imaging, and CT angiography (CTA). Moreover, Ta nanodots maintain robust CT imaging capabilities even at high X-ray energies, and Ta nanodots-based spectral CT achieves metallic artifacts-minimized CTA. The proposed Ta nanodots present substantial potential as a potent CT imaging probe for diagnosing various diseases.

[Retracted] Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 5C were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been submitted for publication elsewhere prior to the submission of this paper to Oncology Reports [Wu X, Cai D, Zhang F, Li M and Wan Q: Long noncoding RNA TUSC7 inhibits cell proliferation, migration and invasion by regulating SOCS4 (SOCS5) expression through targeting miR­616 in endometrial carcinoma. Life Sci 231: 116549, 2019]. In addition, the CACNA203 western blot data shown in Fig. 2A­c and B­C respectively looked strikingly similar, even though different experiments were intended to have been shown in these figure parts. In view of the fact that the contentious data had already apparently been submitted for publication prior to the receipt of this paper at Oncology Reports, and owing to a overall lack of confidence in the presentation of the data, the Editor of has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 43: 121­132, 2020; DOI: 10.3892/or.2019.7396].

Universal Entanglement Spectrum in One-Dimensional Gapless Symmetry Protected Topological States.

Quantum entanglement marks a definitive feature of topological states. However, the entanglement spectrum remains insufficiently explored for topological states without a bulk energy gap. Using a combination of field theory and numerical techniques, we accurately calculate and analyze the entanglement spectrum of gapless symmetry protected topological states in one dimension. We highlight that the universal entanglement spectrum not only encodes the nontrivial edge degeneracy, generalizing the Li-Haldane conjecture to gapless topological states, but also contains the operator content of the underlying boundary conformal field theory. This implies that the bulk wave function can act as a fingerprint of both quantum criticality and topology in gapless symmetry protected topological states. We also identify a symmetry enriched conformal boundary condition that goes beyond the conventional conformal boundary condition.

Supramolecular Nano-Tracker for Real-Time Tracking of Drug Release and Efficient Combination Therapy.

Real-time tracking of drug release from nanomedicine in vivo is crucial for optimizing its therapeutic efficacy in clinical settings, particularly in dosage control and determining the optimal therapeutic window. However, most current real-time tracking systems require a tedious synthesis and purification process. Herein, a supramolecular nano-tracker (SNT) capable of real-time tracking of drug release in vivo based on non-covalent host-guest interactions is presented. By integrating multiple cavities into a single nanoparticle, SNT achieves co-loading of drugs and probes while efficiently quenching the photophysical properties of the probe through host-guest complexation. Moreover, SNT is readily degraded under hypoxic tumor tissues, leading to the simultaneous release of drugs and probes and the fluorescence recovery of probes. With this spatial and temporal consistency in drug loading and fluorescence quenching, as well as drug release and fluorescence recovery, SNT successfully achieves real-time tracking of drug release in vivo (Pearson r = 0.9166, R2 = 0.8247). Furthermore, the released drugs can synergize effectively with fluorescent probes upon light irradiation, achieving potent chemo-photodynamic combination therapy in 4T1-bearing mice with a significantly improved survival rate (33%), providing a potential platform to significantly advance the development of nanomedicine and achieve optimal therapeutic effects in the clinic.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

INTRODUCTION: Subjective cognitive decline (SCD) in amyloid-positive (Aß+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS: In the combined and stratified cohorts, Aß+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aß- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION: Aß+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS: SCD in amyloid-positive (Aß+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aß+ older adults with SCD could be a target population for interventional trials.

fNIRS-Driven Depression Recognition Based on Cross-Modal Data Augmentation.

Early diagnosis and intervention of depression promote complete recovery, with its traditional clinical assessments depending on the diagnostic scales, clinical experience of doctors and patient cooperation. Recent researches indicate that functional near-infrared spectroscopy (fNIRS) based on deep learning provides a promising approach to depression diagnosis. However, collecting large fNIRS datasets within a standard experimental paradigm remains challenging, limiting the applications of deep networks that require more data. To address these challenges, in this paper, we propose an fNIRS-driven depression recognition architecture based on cross-modal data augmentation (fCMDA), which converts fNIRS data into pseudo-sequence activation images. The approach incorporates a time-domain augmentation mechanism, including time warping and time masking, to generate diverse data. Additionally, we design a stimulation task-driven data pseudo-sequence method to map fNIRS data into pseudo-sequence activation images, facilitating the extraction of spatial-temporal, contextual and dynamic characteristics. Ultimately, we construct a depression recognition model based on deep classification networks using the imbalance loss function. Extensive experiments are performed on the two-class depression diagnosis and five-class depression severity recognition, which reveal impressive results with accuracy of 0.905 and 0.889, respectively. The fCMDA architecture provides a novel solution for effective depression recognition with limited data.

Entanglement Structure and Information Protection in Noisy Hybrid Quantum Circuits.

In the context of measurement-induced entanglement phase transitions, the influence of quantum noises, which are inherent in real physical systems, is of great importance and experimental relevance. In this Letter, we present a comprehensive theoretical analysis of the effects of both temporally uncorrelated and correlated quantum noises on entanglement generation and information protection. This investigation reveals that entanglement within the system follows q^{-1/3} scaling for both types of quantum noises, where q represents the noise probability. The scaling arises from the Kardar-Parisi-Zhang fluctuation with effective length scale L_{eff}∼q^{-1}. More importantly, the information protection timescales of the steady states are explored and shown to follow q^{-1/2} and q^{-2/3} scaling for temporally uncorrelated and correlated noises, respectively. The former scaling can be interpreted as a Hayden-Preskill protocol, while the latter is a direct consequence of Kardar-Parisi-Zhang fluctuations. We conduct extensive numerical simulations using stabilizer formalism to support the theoretical understanding. This Letter not only contributes to a deeper understanding of the interplay between quantum noises and measurement-induced phase transition but also provides a new perspective to understand the effects of Markovian and non-Markovian noises on quantum computation.

A hemicyanine-based near-infrared fluorescent probe with large Stokes shift for non-invasive bioimaging of brown adipose tissue.

Brown adipose tissue (BAT), characterized by the presence of numerous mitochondria, plays a key role in metabolism and energy expenditure. Accurately reporting the presence and activation of BAT is beneficial to study obesity, diabetes, and other metabolic disorders. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, non-radioactivity, and simple operation. However, most NIR probes for BAT imaging exhibit small Stokes shifts, which may lead to self-quenching, reducing the signal-to-noise ratio, and introducing cross-talk. Herein, we rationally designed and synthesized a series of hemicyanine-based NIR fluorescent probes HCYBAT-1-3. Among them, HCYBAT-1 demonstrated favorable properties such as near-infrared emission (776 nm), large Stokes shift (139 nm), good biocompatibility and specific mitochondrial targeting (Pearson's colocalization coefficient of 0.87). Meanwhile, HCYBAT-1 was successfully employed to differentiate BAT from white adipose tissue (WAT). Quantitative analysis of NIR fluorescent images showed that HCYBAT-1 could be used for real-time monitoring of BAT activation in mice stimulated by norepinephrine (NE) and cold exposure. Overall, probe HCYBAT-1 showcased its efficacy in non-invasive evaluation of BAT metabolism in vivo with high selectivity and sensitivity.

A Minimalist Iron Oxide Nanoprobe for the High-Resolution Depiction of Stroke by Susceptibility-Weighted Imaging.

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

Real-time detection of gastrointestinal leaks via bismuth chelate-enhanced X-ray gastroenterography.

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

Bismuth drug-inspired ultra-small dextran coated bismuth oxide nanoparticles for targeted computed tomography imaging of inflammatory bowel disease.

Bismuth (Bi)-based computed tomography (CT) imaging contrast agents (CAs) hold significant promise for diagnosing gastrointestinal diseases due to their cost-effectiveness, heightened sensitivity, and commendable biocompatibility. Nevertheless, substantial challenges persist in achieving an easy synthesis process, remarkable water solubility, and effective targeting ability for the potential clinical transformation of Bi-based CAs. Herein, we show Bi drug-inspired ultra-small dextran coated bismuth oxide nanoparticles (Bi2O3-Dex NPs) for targeted CT imaging of inflammatory bowel disease (IBD). Bi2O3-Dex NPs are synthesized through a simple alkaline precipitation reaction using bismuth salts and dextran as the template. The Bi2O3-Dex NPs exhibit ultra-small size (3.4 nm), exceptional water solubility (over 200 mg mL-1), high Bi content (19.75 %), excellent biocompatibility and demonstrate higher X-ray attenuation capacity compared to clinical iohexol. Bi2O3-Dex NPs not only enable clear visualization of the GI tract outline and intestinal loop structures in CT imaging but also specifically target and accumulate at the inflammatory site in colitis mice after oral administration, facilitating a precise diagnosis and enabling targeted CT imaging of IBD. Our study introduces a novel and clinically promising strategy for synthesizing high-performance Bi2O3-Dex NPs for diagnosing gastrointestinal diseases.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

Innovative Multivariable Model Combining MRI Radiomics and Plasma Indexes Predicts Alzheimer's Disease Conversion: Evidence from a 2-Cohort Longitudinal Study.

To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer's disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model's performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor.

Non-Hermitian Moiré Valley Filter.

A valley filter capable of generating a valley-polarized current is a crucial element in valleytronics, yet its implementation remains challenging. Here, we propose a valley filter made of a graphene bilayer which exhibits a 1D moiré pattern in the overlapping region of the two layers controlled by heterostrain. In the presence of a lattice modulation between layers, electrons propagating in one layer can have valley-dependent dissipation due to valley asymmetric interlayer coupling, thus giving rise to a valley-polarized current. Such a process can be described by an effective non-Hermitian theory, in which the valley filter is driven by a valley-resolved non-Hermitian skin effect. Nearly 100% valley polarization can be achieved within a wide parameter range and the functionality of the valley filter is electrically tunable. The non-Hermitian topological scenario of the valley filter ensures high tolerance against imperfections such as disorder and edge defects. Our work opens a new route for efficient and robust valley filters while significantly relaxing the stringent implementation requirements.