Enhanced compound-protein binding affinity prediction by representing protein multimodal information via a coevolutionary strategy.

Due to the lack of a method to efficiently represent the multimodal information of a protein, including its structure and sequence information, predicting compound-protein binding affinity (CPA) still suffers from low accuracy when applying machine-learning methods. To overcome this limitation, in a novel end-to-end architecture (named FeatNN), we develop a coevolutionary strategy to jointly represent the structure and sequence features of proteins and ultimately optimize the mathematical models for predicting CPA. Furthermore, from the perspective of data-driven approach, we proposed a rational method that can utilize both high- and low-quality databases to optimize the accuracy and generalization ability of FeatNN in CPA prediction tasks. Notably, we visually interpret the feature interaction process between sequence and structure in the rationally designed architecture. As a result, FeatNN considerably outperforms the state-of-the-art (SOTA) baseline in virtual drug evaluation tasks, indicating the feasibility of this approach for practical use. FeatNN provides an outstanding method for higher CPA prediction accuracy and better generalization ability by efficiently representing multimodal information of proteins via a coevolutionary strategy.

Photoreversible Aggregation of the Biliprotein Containing the First and Second GAF Domains of a Cyanobacteriochrome All2699 in Nostoc sp. PCC7120.

As plant photoreceptors, phytochromes are capable of detecting red light and far-red light, thereby governing plant growth. All2699 is a photoreceptor found in Nostoc sp. PCC7120 that specifically responds to red light and far-red light. All2699g1g2 is a truncated protein carrying the first and second GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains of All2699. In this study, we found that, upon exposure to red light, the protein underwent aggregation, resulting in the formation of protein aggregates. Conversely, under far-red light irradiation, these protein aggregates dissociated. We delved into the factors that impact the aggregation of All2699g1g2, focusing on the protein structure. Our findings showed that the GAF2 domain contains a low-complexity (LC) loop region, which plays a crucial role in mediating protein aggregation. Specifically, phenylalanine at position 239 within the LC loop region was identified as a key site for the aggregation process. Furthermore, our research revealed that various factors, including irradiation time, temperature, concentration, NaCl concentration, and pH value, can impact the aggregation of All2699g1g2. The aggregation led to variations in Pfr concentration depending on temperature, NaCl concentration, and pH value. In contrast, ΔLC did not aggregate and therefore lacked responses to these factors. Consequently, the LC loop region of All2699g1g2 extended and enhanced sensory properties.

Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

Second-Order Motion-Compensated Echo-Planar Cardiac Diffusion-Weighted MRI: Usefulness of Compressed Sensitivity Encoding.

BACKGROUND: Cardiac diffusion-weighted imaging (DWI) using second-order motion-compensated spin echo (M2C) can provide noninvasive in-vivo microstructural assessment, but limited by relatively low signal-to-noise ratio (SNR). Echo-planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues. PURPOSE: To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI. STUDY TYPE: Prospective. POPULATION: Ten ex-vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis). FIELD STRENGTH/SEQUENCE: 3-T, M2C EPICS DWI, and M2C DWI. ASSESSMENT: The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using aSNR = Mean intensity myocardium / Standard deviation myocardium $$ \mathrm{aSNR}={\mathrm{Mean}\ \mathrm{intensity}}_{\mathrm{myocardium}}/{\mathrm{Standard}\ \mathrm{deviation}}_{\mathrm{myocardium}} $$ , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5-point Likert scale. STATISTICAL TESTS: Bland-Altman analysis and paired t-tests. The threshold for statistical significance was set at P < 0.05. RESULTS: In healthy volunteers, the aSNR with a b-value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in-plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS-M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in-vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in-vivo hearts. DATA CONCLUSION: Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

DEAR model in overweight endometrial cancer patients undergoing fertility-sparing treatment: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of DEAR weight management in overweight patients undergoing fertility-sparing treatment for endometrial cancer or atypical hyperplasia. METHODS: Women with endometrial cancer or atypical hyperplasia who received fertility-sparing treatment and had a body mass index of >25 kg/m2 were randomly allocated to the DEAR (DEAR weight management) and control (self weight management) groups. Body morphology and composition, glycolipid metabolism, and tumor outcomes were assessed in both groups before and at 3 and 6 months after intervention. RESULTS: Overall, 72 subjects were included (36 in each group). Following intervention, the DEAR group showed significantly lower median body weight (69.45 vs. 78.05), body mass index (26.19 vs. 29.15), lipid accumulation index (29.21 vs. 57.86), body fat mass (24.00 vs. 29.30), visceral fat area (112.5 vs. 133.3), and glycolipid metabolic indices (except high density lipoprotein) than the control group (P < 0.05) and showed a decreasing trend. The test group achieved significantly higher complete remission (88.46% vs. 57.14%; P < 0.05); the time to complete remission did not differ significantly (P > 0.05). CONCLUSIONS: DEAR weight management can improve the studied parameters and complete remission rates in this population. REGISTRATION: NCT06169449.

αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR)-specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models; however, the related mechanisms remain unclear. Here, we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection-induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks had no effect on the mice's normal pain threshold or locomotor activity and anxiety-like behavior, as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA sequencing results identified 209 differentially expressed genes (DEGs) in the CIPN model, and simultaneously injecting GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by the cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin-induced CIPN management.

Assessment of the effectiveness of the BOPPPS model combined with case-based learning on nursing residency education for newly recruited nurses in China: a mixed methods study.

BACKGROUND: Expanding new nurse training and education is a priority for nursing educators as well as a critical initiative to stabilize the nursing workforce. Given that there is currently no standardized program for the training of new nurses in China, we investigated the effectiveness of the bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary model combined with case-based learning ((BOPPPS-CBL) for the standardized training of new nurses. METHODS: The mixed method approach with explanatory sequential (quantitative-qualitative) method was used. A questionnaire was used to compare the impact of the BOPPPS-CBL model and the Traditional Learning Model (TLM) on the core competencies of 185 new nurses for two years of standardized training. Quantitative data were analyzed using SPSS 22.0. Focus group interviews were used with four groups of new nurses and perceptions of BOPPPS-CBL training were recorded. Qualitative data were analyzed thematically. RESULTS: According to the quantitative data, more new nurses agreed that the BOPPPS-CBL model stimulated their learning and improved their core nursing competencies than the TLM. The BOPPPS-CBL group outperformed the TLM group on theoretical knowledge tests. Qualitative data revealed that 87.5% of new nurses agreed on the value of BOPPPS-CBL training, and three themes were extracted: (1) role promotion; (2) formation of new thinking to solve clinical problems; and (3) suggestions for improvement. CONCLUSION: BOPPPS-CBL training had a significant impact on improving new nurses' core competencies and promoting the transition of new nurses to clinical practice nurses in China. The study recommends BOPPPS-CBL training as an effective teaching model for the standardized training and education of new nurses.

Structure Reveals the Impact of Surface Charge Distribution on the Phase Separation and Aggregation of Slr0280.

Liquid-liquid phase separation (LLPS) plays a key role in the regulation of life activities. Here, we reported a protein from Synechocystis sp. PCC 6803 and annotated as Slr0280. To obtain a water-soluble protein, we deleted the N-terminus transmembrane domain and named it Slr0280Δ. Slr0280Δ with high concentration can undergo LLPS at a low temperature in vitro. It belongs to the phosphodiester glycosidase family of proteins and has a segment of a low-complexity sequence region (LCR), which is thought to regulate the LLPS. Our results show that electrostatic interactions impact the LLPS of Slr0280Δ. We also acquired the structure of Slr0280Δ, which has many grooves on the surface with a large distribution of positive and negative charges. This may be advantageous for the LLPS of Slr0280Δ through electrostatic interactions. Furthermore, the conserved amino acid (arginine at position 531) located on the LCR is important for maintaining the stability of Slr0280Δ as well as LLPS. Our research indicated that the LLPS of proteins can be transformed into aggregation by changing the surface charge distribution.

Research progress on the role of ET-1 in diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the common complications of diabetes mellitus, which usually progresses to end-stage renal disease and causes great damage to the health of patients. Endothelin-1 (ET-1), a molecule closely associated with the progression of DKD, has increased expression in response to high glucose stimulation and is involved in hemodynamic changes, inflammation, glomerular and tubular dysfunction in the kidney, causing an increase in proteinuria and a decrease in glomerular filtration function, ultimately leading to glomerulosclerosis and renal failure. This paper aims to review the molecular level changes, regulatory mechanisms, and mechanisms of action of ET-1 under DKD, clinical trials of ET-1 receptor antagonists in recent years and current problems, to provide basic information and new research directions and ideas for the treatment of DKD and ET-1-related research.

High-Titer Self-Propagating Capsidless Chikungunya Virus Generated in Vero Cells as a Strategy for Alphavirus Vaccine Development.

In our previous study, we found that a new type of Chikungunya virus particle with a complete capsid deletion (ΔC-CHIKV) is still infectious in BHK-21 cells and demonstrated its potential as a live attenuated vaccine candidate. However, the low yield as well as the disability to propagate in vaccine production cell line Vero of ΔC-CHIKV are not practical for commercial vaccine development. In this study, we not only achieved the successful propagation of the viral particle in Vero cells, but significantly improved its yield through construction of a chimeric VEEV-ΔC-CHIKV and extensive passage in Vero cells. Mechanistically, high production of VEEV-ΔC-CHIKV is due to the improvement of viral RNA packaging efficiency conferred by adaptive mutations, especially those in envelope proteins. Similar to ΔC-CHIKV, the passaged VEEV-ΔC-CHIKV is safe, immunogenic, and efficacious, which protects mice from CHIKV challenge after only one shot of immunization. Our study demonstrates that the utilization of infectious capsidless viral particle of CHIKV as a vaccine candidate is a practical strategy for the development of alphavirus vaccine. IMPORTANCE Chikungunya virus (CHIKV) is one of important emerging alphaviruses. Currently, there are no licensed vaccines against CHIKV infection. We have previously found a new type of Chikungunya virus particle with a complete capsid deletion (ΔC-CHIKV) as a live attenuated vaccine candidate that is not suitable for commercial vaccine development with the low viral titer production. In this study, we significantly improved its production through construction of a chimeric VEEV-ΔC-CHIKV. Our results proved the utilization of infectious capsidless viral particle of CHIKV as a safe and practical vaccine candidate.

LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346.

Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

Enzymatic glucosylation of polyphenols using glucansucrases and branching sucrases of glycoside hydrolase family 70.

Polyphenols exhibit various beneficial biological activities and represent very promising candidates as active compounds for food industry. However, the low solubility, poor stability and low bioavailability of polyphenols have severely limited their industrial applications. Enzymatic glycosylation is an effective way to improve the physicochemical properties of polyphenols. As efficient transglucosidases, glycoside hydrolase family 70 (GH70) glucansucrases naturally catalyze the synthesis of polysaccharides and oligosaccharides from sucrose. Notably, GH70 glucansucrases show broad acceptor substrate promiscuity and catalyze the glucosylation of a wide range of non-carbohydrate hydroxyl group-containing molecules, including benzenediol, phenolic acids, flavonoids and steviol glycosides. Branching sucrase enzymes, a newly established subfamily of GH70, are shown to possess a broader acceptor substrate binding pocket that acts efficiently for glucosylation of larger size polyphenols such as flavonoids. Here we present a comprehensive review of glucosylation of polyphenols using GH70 glucansucrase and branching sucrases. Their catalytic efficiency, the regioselectivity of glucosylation and the structure of generated products are described for these reactions. Moreover, enzyme engineering is effective for improving their catalytic efficiency and product specificity. The combined information provides novel insights on the glucosylation of polyphenols by GH70 glucansucrases and branching sucrases, and may promote their applications.

Machine learning-based multiparametric magnetic resonance imaging radiomics model for distinguishing central neurocytoma from glioma of lateral ventricle.

OBJECTIVES: To develop a machine learning-based radiomics model based on multiparametric magnetic resonance imaging (MRI) for preoperative discrimination between central neurocytomas (CNs) and gliomas of lateral ventricles. METHODS: A total of 132 patients from two medical centers were enrolled in this retrospective study. Patients from the first medical center were divided into a training cohort (n = 74) and an internal validation cohort (n = 30). Patients from the second medical center were used as the external validation cohort (n = 28). Features were extracted from contrast-enhanced T1-weighted and T2-weighted images. A support vector machine was used for radiomics model investigation. Performance was evaluated using the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The model's performance was also compared with those of three radiologists. RESULTS: The radiomics model achieved an AUC of 0.986 in the training cohort, 0.933 in the internal validation cohort, and 0.903 in the external validation cohort. In the three cohorts, the AUC values were 0.657, 0.786, and 0.708 for radiologist 1; 0.838, 0.799, and 0.790 for radiologist 2; and 0.827, 0.871, and 0.862 for radiologist 3. When assisted by the radiomics model, two radiologists improved their performance in the training cohort (p < 0.05) but not in the internal or external validation cohorts. CONCLUSIONS: The machine learning radiomics model based on multiparametric MRI showed better performance for distinguishing CNs from lateral ventricular gliomas than did experienced radiologists, and it showed the potential to improve radiologist performance. KEY POINTS: • The machine learning radiomics model shows excellent performance in distinguishing CNs from gliomas. • The radiomics model outweighs two experienced radiologists (area under the receiver operating characteristic curve, 0.90 vs 0.79 and 0.86, respectively). • The radiomics model has the potential to enhance radiologist performance.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in asymptomatic heart-transplanted patients.

OBJECTIVES: To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). METHODS: From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. RESULTS: During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. CONCLUSION: Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. KEY POINTS: • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

Ringlike late gadolinium enhancement provides incremental prognostic value in non-classical arrhythmogenic cardiomyopathy.

BACKGROUND: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. METHODS: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. RESULTS: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13-56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89-54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). CONCLUSION: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

Aberrant Topological Properties of Brain Functional Network in Children with Obstructive Sleep Apnea Derived from Resting-State fMRI.

To examine the difference in the topological properties of brain functional network between the children with obstructive sleep apnea (OSA) and healthy controls, and to explore the relationships between these properties and cognitive scores of OSA children. Twenty-four OSA children (6.5 ± 2.8 years, 15 males) and 26 healthy controls (8.0 ± 2.9 years, 11 males) underwent resting-state fMRI (rs-fMRI), based on which brain functional networks were constructed. We compared the global and regional topological properties of the network between OSA children and healthy controls. Partial correlation analysis was performed between topological properties and cognitive scores across OSA children. When comparing the OSA children with the healthy controls, lower full-scale intelligent quotient (FIQ) and verbal intelligent quotient (VIQ) were observed. Additionally, nodal degree centrality decreased in the bilateral anterior cingulate and paracingulate gyrus, but increased in the right middle frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Nodal efficiency decreased in the right precentral gyrus, and the bilateral anterior cingulate and paracingulate gyrus, but increased in the left fusiform gyrus. Nodal betweenness centrality increased in the dorsolateral part of the right superior frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Further, the nodal degree centrality in the left supramarginal gyrus was positively correlated with FIQ. In contrast, none of global topological properties showed difference between those two groups. The outcomes of OSA may impaired the regional topological properties of the brain functional network of OSA children, which may be potential neural mechanism underlying the cognitive declines of these patients.

Stable perovskite solar cells with 22% efficiency enabled by inhibiting migration/loss of iodide ions.

Iodide ions (I- and I3-) in perovskites tend to migrate resulting in phase segregation and degradation of perovskite films and devices under illumination or operation conditions. In order to overcome this intrinsic difficulty, passivation and additive strategies have been developed in many studies. In this work, we introduced polyetheramine (PEA) into perovskite films to inhibit the migration and loss of iodides and suppress defects related to these migrated ions. The perovskite films with PEA barely suffered iodide loss even under long-term ultraviolet (UV) illumination and possessed a lower trap density than that of the pristine films before and after aging under UV illumination. Density functional theory (DFT) calculations revealed that PEA can form strong interactions with iodides and Pb2+ in perovskites via PbO and H-I bonds, and the iodide ions (I- and I3-) could be locked firmly by PEA, preventing them from migration or loss. Using this method, the efficiency of perovskite solar cells (PSCs) can be improved from 19.71% (without PEA) to 22.02% (with PEA). After 200 h of maximum power point (MPP) tracking, the efficiency of PSCs with PEA remained 89% of its initial value and that of PSCs without PEA fully degraded.

Biomimetic platelet-camouflaged drug-loaded polypyrrole for the precise targeted antithrombotic therapy.

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.

The comparison of diffusion tensor imaging in human hearts between 1.5 T and 3.0 T.

BACKGROUND: The aim was to compare the diffusion tensor imaging (DTI) indices derived from human hearts between 1.5 T and 3.0 T scanners. Additionally, the reproducibility of DTI indices was assessed between 1.5 T and 3.0 T scanners. METHODS: A total of 18 ex-vivo hearts were derived from patients who underwent heart transplantation. The DTI schemes were performed at 1.5 T and 3.0 T, respectively. Then, the same slices from each ex-vivo heart were selected for image analysis. The student's t-test or Wilcoxon-rank test was used to compare the statistical differences. The agreement of DTI indices was mainly reported as the interclass correlation coefficient (ICC). RESULTS: No significant differences (all P > 0.05) were found in the DTI indices between 1.5 T and 3.0 T scanners. Interestingly, the ICC of all DTI indices was relatively lower with a low b-value. The reproducibility of the helix angle (HA) was relatively lower when compared to the other DTI indices. CONCLUSION: The DTI indices of ex-vivo human hearts between 1.5 T and 3.0 T scanners had no significant differences. The consistency of DTI indices needed caution using a low b-value with different field strengths, and the relatively low reproducibility of HA should be considered.