TSHR signaling promotes hippocampal dependent memory formation through modulating Wnt5a/ß-catenin mediated neurogenesis.

Subclinical hyperthyroidism is defined biochemically as a low or undetectable thyroid-stimulating hormone (TSH) with normal thyroid hormone levels. Low TSHR signaling is considered to associate with cognitive impairment. However, the underlying molecular mechanism by which TSHR signaling modulates memory is poorly understood. In this study, we found that Tshr-deficient in the hippocampal neurons impairs the learning and memory abilities of mice, accompanying by a decline in the number of newborn neurons. Notably, Tshr ablation in the hippocampus decreases the expression of Wnt5a, thereby inactivating the ß-catenin signaling pathway to reduce the neurogenesis. Conversely, activating of the Wnt/ß-catenin pathway by the agonist SKL2001 results in an increase in hippocampal neurogenesis, resulting in the amelioration in the deficits of memory caused by Tshr deletion. Understanding how TSHR signaling in the hippocampus regulates memory provides insights into subclinical hyperthyroidism affecting cognitive function and will suggest ways to rationally design interventions for neurocognitive disorders.

Treatment strategies for hepatic artery complications after pediatric liver transplantation: A systematic review.

This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure.

The impact of type 2 diabetes mellitus on the clinical profile, myocardial fibrosis, and prognosis in non-ischemic dilated cardiomyopathy: a prospective cohort study.

BACKGROUND: The impact of the coexistence of type 2 diabetes mellitus (T2DM) in patients with non-ischemic dilated cardiomyopathy (DCM) on clinical profiles, myocardial fibrosis, and outcomes remain incompletely understood. METHOD: A total of 1152 patients diagnosed with non-ischemic DCM were prospectively enrolled from June 2012 to October 2021 and categorized into T2DM and non-T2DM groups. Clinical characteristics, cardiac function, and myocardial fibrosis evaluated by CMR were compared between the two groups. The primary endpoint included both all-cause mortality and heart transplantation. Cause of mortality was classified into heart failure death, sudden cardiac death, and non-cardiac death. Cox regression analysis and Kaplan-Meier analysis were performed to identify the association between T2DM and clinical outcomes. Propensity score matching (PSM) cohort including 438 patients was analyzed to reduce the bias from confounding covariates. RESULTS: Among the 1152 included DCM patients, 155 (13%) patients had T2DM. Patients with T2DM were older (55 ± 12 vs. 47 ± 14 years, P < 0.001), had higher New York Heart Association (NYHA) functional class (P = 0.003), higher prevalence of hypertension (37% vs. 21%, P < 0.001), atrial fibrillation (31% vs. 16%, P < 0.001), lower left ventricular (LV) ejection fraction (EF) (23 ± 9% vs. 27 ± 12%, P < 0.001), higher late gadolinium enhancement (LGE) presence (55% vs. 45%, P = 0.02), and significantly elevated native T1 (1323 ± 81ms vs. 1305 ± 73ms, P = 0.01) and extracellular volume fraction (ECV) (32.7 ± 6.3% vs. 31.3 ± 5.9%, P = 0.01) values. After a median follow-up of 38 months (interquartile range: 20-57 months), 239 patients reached primary endpoint. Kaplan-Meier analysis showed that patients with T2DM had worse clinical outcomes compared with those without T2DM in the overall cohort (annual events rate: 10.2% vs. 5.7%, P < 0.001). T2DM was independently associated with an increased risk of primary endpoint in the overall (Hazard ratio [HR]: 1.61, 95% CI: 1.13-2.33, P = 0.01) and PSM (HR: 1.54, 95% CI: 1.05-2.24, P = 0.02) cohorts. Furthermore, T2DM was associated with a higher risk of heart failure death (P = 0.006) and non-cardiac death (P = 0.02), but not sudden cardiac death (P = 0.16). CONCLUSIONS: Patients with T2DM represented a more severe clinical profile and experienced more adverse outcomes compared to those without T2DM in a large DCM cohort. TRIAL REGISTRATION: Trial registration number: ChiCTR1800017058; URL: https://www. CLINICALTRIALS: gov .

Fast measurement of coherence-orbital angular momentum matrices of random light beams using off-axis holography and coordinate transformation.

We propose an effective protocol to measure the coherence-orbital angular momentum (COAM) matrix of an arbitrary partially coherent beam. The method is based on an off-axis holography scheme and the Cartesian-polar coordinate transformation, which enables to simultaneously deal with all the COAM matrix elements of interest. The working principle is presented and discussed in detail. A proof-of-principle experiment is carried out to reconstruct the COAM matrices of partially coherent beams with spatially uniform and non-uniform coherence states. We find an excellent agreement between the experimental results and the theoretical predictions. In addition, we show that the OAM spectrum of a partially coherent beam can also be directly acquired from the measured COAM matrix.

Enabling endogenous distributed acoustic sensing in a digital subcarrier coherent transmission system.

To monitor the health of the fiber network and its ambient environment in densely populated access/metro network areas, in this Letter, an endogenous distributed acoustic sensing (DAS) has been proposed and achieved in a coherent digital subcarrier multiplexing (DSCM) system. Rather than specially allocating a sensing probe in general integrated communication and sensing schemes, the fractional Fourier transformed (FrFT) training sequence (TS) designated for time/frequency synchronization in DSCM coherent communications has been repurposed for sensing. While achieving excellent synchronization performance of communication, the FrFT-based TS can also be concurrently utilized to perform distributed vibration sensing. Experimental results demonstrate that the FrFT-based timing/frequency synchronization sequence is repurposed to achieve a DAS sensitivity of 70 p ε/Hz at a spatial resolution of 5 m, along with 100-Gb/s 16 quadrature amplitude modulation (QAM) DSCM transmission, without a loss of spectral efficiency.

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. PURPOSE: Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. STUDY TYPE: Prospective. POPULATION: Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). FIELD STRENGTH/SEQUENCE: Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. ASSESSMENT: Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. STATISTICAL TESTS: Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. RESULTS: 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. DATA CONCLUSIONS: Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Reference Ranges of Ventricular Morphology and Function in Healthy Chinese Adults: A Multicenter 3 T MRI Study.

BACKGROUND: Magnetic resonance imaging (MRI) reference ranges for ventricular morphology and function in the Chinese population are lacking. PURPOSE: To establish the MRI reference ranges of left and right ventricular (LV and RV) morphology and function based on a large multicenter cohort. STUDY TYPE: Prospective. POPULATION: One thousand and twelve healthy Chinese Han adults. FIELD STRENGTH/SEQUENCE: Balanced steady-state free procession cine sequence at 3.0 T. ASSESSMENT: Biventricular end-diastolic, end-systolic, stroke volume, and ejection fraction (EDV, ESV, SV, and EF), LV mass (LVM), end-diastolic and end-systolic dimension (LVEDD and LVESD), anteroseptal wall thickness (AS), and posterolateral wall thickness (PL) were measured. Body surface area (BSA) and height were used to index biventricular parameters. Parameters were compared between age groups and sex. STATISTICAL TESTS: Independent-samples t-tests or Mann-Whitney U test to compare mean values between sexes; ANOVA or Kruskal-Wallis test to compare mean values among age groups; linear regression to assess the relationships between cardiac parameters and age (correlation coefficient, r). A P value <0.05 was considered statistically significant. RESULTS: The biventricular volumes, LVM, LVEDD, RVEDV/LVEDV ratio, LVESD, AS, and PL were significantly greater in males than in females, even after indexing to BSA or height, while LVEF and RVEF were significantly lower in males than in females. For both sexes, age was significantly negatively correlated with biventricular volumes (male and female: LVEDV [r = -0.491; r = -0.373], LVESV [r = -0.194; r = -0.184], RVEDV [r = -0.639; r = -0.506], RVESV [r = -0.270; r = -0.223]), with similar correlations after BSA normalization. LVEF (r = 0.043) and RVEF (r = 0.033) showed a significant correlation with age in females, but not in males (P = 0.889; P = 0.282). DATA CONCLUSION: MRI reference ranges for biventricular morphology and function in Chinese adults are presented and show significant associations with age and sex. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Nidogen-2 is a Novel Endogenous Ligand of LGR4 to Inhibit Vascular Calcification.

BACKGROUND: Vascular calcification is closely related to the all-cause mortality of cardiovascular events. Basement membrane protein nidogen-2 is a key component of the vascular extracellular matrix microenvironment and we recently found it is pivotal for the maintenance of contractile phenotype in vascular smooth muscle cells (VSMCs). However, whether nidogen-2 is involved in VSMCs osteochondrogenic transition and vascular calcification remains unclear. METHODS: VSMCs was treated with high-phosphate to study VSMC calcification in vitro. Three different mice models (5/6 nephrectomy-induced chronic renal failure, cholecalciferol-overload, and periadventitially administered with CaCl2) were used to study vascular calcification in vivo. Membrane protein interactome, coimmunoprecipitation, flow cytometric binding assay, surface plasmon resonance, G protein signaling, VSMCs calcium assays were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Nidogen-2 protein levels were significantly reduced in calcified VSMCs and aortas from mice in different vascular calcification model. Nidogen-2 deficiency exacerbated high-phosphate-induced VSMC calcification, whereas the addition of purified nidogen-2 protein markedly alleviated VSMC calcification in vitro. Nidogen-2-/- mice exhibited aggravated aorta calcification compared to wild-type (WT) mice in response to 5/6 nephrectomy, cholecalciferol-overload, and CaCl2 administration. Further unbiased coimmunoprecipitation and interactome analysis of purified nidogen-2 and membrane protein in VSMCs revealed that nidogen-2 directly binds to LGR4 (leucine-rich repeat G-protein-coupled receptor 4) with KD value 26.77 nM. LGR4 deficiency in VSMCs in vitro or in vivo abolished the protective effect of nidogen-2 on vascular calcification. Of interest, nidogen-2 biased activated LGR4-Gαq-PKCα (protein kinase Cα)-AMPKα1 (AMP-activated protein kinase α1) signaling to counteract VSMCs osteogenic transition and mineralization. CONCLUSIONS: Nidogen-2 is a novel endogenous ligand of LGR4 that biased activated Gαq- PKCα-AMPKα1 signaling and inhibited vascular calcification.

Long-term changes in frailty and incident type 2 diabetes: A prospective cohort study based on the UK Biobank.

AIMS: To estimate the association between long-term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. METHODS: We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow-up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow-up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33-1.43) and 1.69 (95% CI 1.59-1.79), respectively (both p < 0.001), in the multivariable-adjusted model. During a median follow-up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1-point increase in the final FP was associated with a 25% (95% CI 1.14-1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5-point/year increase in ΔFP was associated with a 52% (95% CI 1.18-1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00-4.58; p < 0.001). Using the frailty index did not materially change the results. CONCLUSIONS: Long-term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk.

Prognostic value of mid-term cardiovascular magnetic resonance follow-up in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study.

BACKGROUND: The prognostic value of follow-up cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) patients is unclear. We aimed to investigate the prognostic value of cardiac function, structure, and tissue characteristics at mid-term CMR follow-up. METHODS: The study population was a prospectively enrolled cohort of DCM patients who underwent guideline-directed medical therapy with baseline and follow-up CMR, which included measurement of biventricular volume and ejection fraction, late gadolinium enhancement, native T1, native T2, and extracellular volume. During follow-up, major adverse cardiac events (MACE) were defined as a composite endpoint of cardiovascular death, heart transplantation, and heart-failure readmission. RESULTS: Among 235 DCM patients (median CMR interval: 15.3 months; interquartile range: 12.5-19.2 months), 54 (23.0%) experienced MACE during follow-up (median: 31.2 months; interquartile range: 20.8-50.0 months). In multivariable Cox regression, follow-up CMR models showed significantly superior predictive value than baseline CMR models. Stepwise multivariate Cox regression showed that follow-up left ventricular ejection fraction (LVEF; hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.91-0.96; p < 0.001) and native T1 (HR, 1.01; 95% CI, 1.00-1.01; p = 0.030) were independent predictors of MACE. Follow-up LVEF ≥ 40% or stable LVEF < 40% with T1 ≤ 1273 ms indicated low risk (annual event rate < 4%), while stable LVEF < 40% and T1 > 1273 ms or LVEF < 40% with deterioration indicated high risk (annual event rate > 15%). CONCLUSIONS: Follow-up CMR provided better risk stratification than baseline CMR. Improvements in the LVEF and T1 mapping are associated with a lower risk of MACE.

Graphitized Carbon-Supported Co@Co3O4 for Ozone Decomposition over the Entire Humidity Range.

Ground-level ozone (O3) pollution has emerged as a significant concern due to its detrimental effects on human health and the ecosystem. Catalytic removal of O3 has proven to be the most efficient and cost-effective method. However, its practical application faces substantial challenges, particularly in relation to its effectiveness across the entire humidity range. Herein, we proposed a novel strategy termed "dual active sites" by employing graphitized carbon-loaded core-shell cobalt catalysts (Co@Co3O4-C). Co@Co3O4-C was synthesized via the pyrolysis of a Co-organic ligand as the precursor. By utilizing this approach, we achieved a nearly constant 100% working efficiency of the Co@Co3O4-C catalyst for catalyzing O3 decomposition across the entire humidity range. Physicochemical characterization coupled with density functional theory calculations elucidates that the presence of encapsulated metallic Co nanoparticles enhances the reactivity of the cobalt oxide capping layer. Additionally, the interface carbon atom, strongly influenced by adjacent metallic Co nuclei, functions as a secondary active site for the decomposition of O3 decomposition. The utilization of dual active sites effectively mitigates the competitive adsorption of H2O molecules, thus isolating them for adsorption in the cobalt oxide capping layer. This optimized configuration allows for the decomposition of O3 without interference from moisture. Furthermore, O3 decomposition monolithic catalysts were synthesized using a material extrusion-based three-dimensional (3D) printing technology, which demonstrated a low pressure drop and exceptional mechanical strength. This work provides a "dual active site" strategy for the O3 decomposition reaction, realizing O3 catalytic decomposition over the entire humidity range.

Role of the In-Situ-Formed Surface (Pt-S-O)-Ti Active Structure in SO2-Promoted C3H8 Combustion over a Pt/TiO2 Catalyst.

Typically, SO2 unavoidably deactivates catalysts in most heterogeneous catalytic oxidations. However, for Pt-based catalysts, SO2 exhibits an extraordinary boosting effect in propane catalytic oxidation, but the promotive mechanism remains contentious. In this study, an in situ-formed tactful (Pt-S-O)-Ti structure was concluded to be a key factor for Pt/TiO2 catalysts with a substantial SO2 tolerance ability. The experiments and theoretical calculations confirm that the high degree of hybridization and orbital coupling between Pt 5d and S 3p orbitals enable more charge transfer from Pt to S species, thus forming the (Pt-S-O)-Ti structure with the oxygen atom dissociated from the chemisorbed O2 adsorbed on oxygen vacancies. The active oxygen atom in the (Pt-S-O)-Ti active structure is a robust site for C3H8 adsorption, leading to a better C3H8 combustion performance. This work can provide insights into the rational design of chemical bonds for high SO2 tolerance catalysts, thereby improving economic and environmental benefits.

Management of Isolated Abdominal Aortic Dissection: Indications and Strategies for Treatment.

BACKGROUND: The aim of this paper was to report our experience in the management of isolated abdominal aortic dissection with endovascular aortic repair and conservative treatment. METHODS: A cohort of 22 consecutive patients with isolated abdominal aortic dissection was treated between January 2016 and December 2021. We reviewed the demographics, clinical features, therapeutic modalities and follow-up results. Retrospective data analysis from patient charts was performed. RESULTS: Twenty-two patients were enrolled in this study from 2 centers. The mean age was 66.2 ± 13.3 years. Hypertension was the primary risk factor. Seventeen (72.7%) patients were asymptomatic, and 18 patients were subrenal artery type (type II). A total of 12 patients had successful endovascular repair (EVAR), and 10 patients underwent conservative treatment. In the group receiving conservative treatment, no patients required EVAR during follow-up, and 4 patients died. However, none of them had aortic causes: 2 patients had cardiac causes, the other 2 had cancer, and the others remained symptom-free. The latest computed tomographic angiography images showed that abdominal aortic dissection still existed, and the extent of the false lumen did not increase significantly. CONCLUSIONS: Both conservative treatment and EVAR are effective treatment options. Appropriate treatment needs to be performed according to different patients' clinical manifestations and doctors' experience.

Evaluation of activities of daily living using an electronic version of the Longshi Scale in patients with stroke: reliability, consistency, and preference.

BACKGROUND: The Longshi Scale is a pictorial assessment tool for evaluating activities of daily living (ADL) in patients with stroke. The paper-based version presents challenges; thus, the WeChat version was created to enhance accessibility. Herein, we aimed to validate the inter-rater and test-retest reliabilities of the WeChat version of the Longshi Scale and explore its potential clinical applications. METHODS: We recruited 115 patients with stroke in the study. The ADL results of each patient were assessed using both the WeChat and paper-based version of the Longshi Scale; each evaluation was conducted by 28 health professionals and 115 caregivers separately. To explore the test-retest reliability of the WeChat version, 22 patients were randomly selected and re-evaluated by health professionals using the WeChat version. All evaluation criteria were recorded, and all evaluators were surveyed to indicate their preference between the two versions. RESULTS: Consistency between WeChat and the paper-based Longshi Scale was high for ADL scores by health professionals (ICC2,1 = 0.803-0.988) and caregivers (ICC2,1 = 0.845-0.983), as well as for degrees of disability (κw = 0.870 by professionals; κw = 0.800 by caregivers). Bland-Altman analysis showed no significant discrepancies. The WeChat version exhibited good test-retest reliability (κw = 0.880). The WeChat version showed similar inter-rater reliability in terms of the ADL score evaluated using the paper-based version (ICC2,1 = 0.781-0.941). The time to complete assessments did not differ significantly, although the WeChat version had a shorter information entry time (P < 0.001, 95% confidence interval: -43.463 to -15.488). Health professionals favored the WeChat version (53.6%), whereas caregivers had no significant preference. CONCLUSIONS: The WeChat version of the Longshi Scale is reliable and serves as a suitable alternative for health professionals and caregivers to assess ADL levels in patients with stroke. The WeChat version of the Longshi Scale is considered user-friendly by health professionals, although it is not preferred by caregivers. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Second People's Hospital of Shenzhen (approval number: 20210812003-FS01) and registered on the Clinical Trial Register Center website: clinicaltrials.gov on January 31, 2022 (registration no.: NCT05214638).

Design, construction and application of algae-bacteria synergistic system for treating wastewater.

The wastewater treatment technology of algae-bacteria synergistic system (ABSS) is a promising technology which has the advantages of low energy consumption, good treatment effect and recyclable high-value products. In this treatment technology, the construction of an ABSS is a very important factor. At the same time, the emergence of some new technologies (such as microbial fuel cells and bio-carriers, etc.) has further enriched constructing the novel ABSS, which could improve the efficiency of wastewater treatment and the biomass harvesting rate. Thus, this review focuses on the construction of a novel ABSS in wastewater treatment in order to provide useful suggestions for the technology of wastewater treatment.

Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition.

G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed in nonolfactory tissues and emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of a larger mechanism for odor discrimination. Here, we demonstrate that the OR extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid over the orthosteric pocket. We demonstrate using molecular dynamics simulations that ECL2 controls the shape and volume of the odorant-binding pocket, maintains the pocket hydrophobicity, and acts as a gatekeeper of odorant binding. Therefore, we propose the interplay between the specific orthosteric pocket and the variable, less specific ECL2 controls OR specificity and promiscuity. Furthermore, the 3D models created here enabled virtual screening of new OR agonists and antagonists, which exhibited a 70% hit rate in cell assays. Our approach can potentially be generalized to structure-based ligand screening for other G protein-coupled receptors that lack high-resolution 3D structures.

A positive feedback circuit driven by m6A-modified circular RNA facilitates colorectal cancer liver metastasis.

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Cardiac MRI to Predict Sudden Cardiac Death Risk in Dilated Cardiomyopathy.

Background Sudden cardiac death (SCD) is one of the leading causes of death in individuals with nonischemic dilated cardiomyopathy (DCM). However, the risk stratification of SCD events remains challenging in clinical practice. Purpose To determine whether myocardial tissue characterization with cardiac MRI could be used to predict SCD events and to explore a SCD stratification algorithm in nonischemic DCM. Materials and Methods In this prospective single-center study, adults with nonischemic DCM who underwent cardiac MRI between June 2012 and August 2020 were enrolled. SCD-related events included SCD, appropriate implantable cardioverter-defibrillator shock, and resuscitation after cardiac arrest. Competing risk regression analysis and Kaplan-Meier analysis were performed to identify the association of myocardial tissue characterization with outcomes. Results Among the 858 participants (mean age, 48 years; age range, 18-83 years; 603 men), 70 (8%) participants experienced SCD-related events during a median follow-up of 33.0 months. In multivariable competing risk analysis, late gadolinium enhancement (LGE) (hazard ratio [HR], 1.87; 95% CI: 1.07, 3.27; P = .03), native T1 (per 10-msec increase: HR, 1.07; 95% CI: 1.04, 1.11; P < .001), and extracellular volume fraction (per 3% increase: HR, 1.26; 95% CI: 1.11, 1.44; P < .001) were independent predictors of SCD-related events after adjustment of systolic blood pressure, atrial fibrillation, and left ventricular ejection fraction. An SCD risk stratification category was developed with a combination of native T1 and LGE. Participants with a native T1 value 4 or more SDs above the mean (1382 msec) had the highest annual SCD-related events rate of 9.3%, and participants with a native T1 value 2 SDs below the mean (1292 msec) and negative LGE had the lowest rate of 0.6%. This category showed good prediction ability (C statistic = 0.74) and could be used to discriminate SCD risk and competing heart failure risk. Conclusion Myocardial tissue characteristics derived from cardiac MRI were independent predictors of sudden cardiac death (SCD)-related events in individuals with nonischemic dilated cardiomyopathy and could be used to stratify participants according to different SCD risk categories. Clinical trial registration no. ChiCTR1800017058 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sakuma in this issue.

High-security constellation shaped self-homodyne coherent system with 4-D joint encryption.

In recent years, the self-homodyne coherent (SHC) system and the constellation shaping (CS) technique have drawn considerable attention due to their abilities to further improve the transmission capacity for various scenarios. From the security point of view, the CS technique and the SHC infrastructure also provide new dimensions for encryption. We propose a high-security and reliable SHC system based on the CS technique and the digital chaos. With a four-dimensional hyperchaotic system, chaotic sequences are generated and used for the exclusive or operation, chaotic constant composition distribution matching, phase disturbance, and optical-layer time-delay disturbance. Moreover, 64-ary circular quadrature amplitude modulation (64CQAM) format is adopted for transmission due to its advantages of sensitivity to phase noise, immunity to conventional digital signal processing, and ability of time-mismatch masking, which is verified by simulation in a SHC system. Last, we conduct an experimental verification in a 20GBaud probabilistically shaped 64CQAM SHC system. Consequently, with a large-linewidth laser source, optical-layer security can be protected by time mismatches of tens of picoseconds. And the digital-layer security is protected by an enormous key space of 10127. The proposed scheme can provide reliable real-time encryption for the optical fiber transmission, serving as a potential candidate for the future high-capacity inter/intra-datacenter security interconnect.

Propagation of coherence-OAM matrix of an optical beam in vacuum and turbulence.

Propagation of the coherence-orbital angular momentum (COAM) matrix of partially coherent beams in homogeneous and isotropic turbulence, e.g., atmosphere, is formulated using the extended Huygens-Fresnel principle. It is found that under the effect of turbulence the elements in the COAM matrix will generally be affected by other elements, resulting in certain OAM mode dispersion. We show that if turbulence is homogeneous and isotropic, there exists an analytic "selection rule" for governing such a dispersion mechanism, which states that only the elements having the same index difference, say l - m, may interact with each other, where l and m denote OAM mode indices. Further, we develop a wave-optics simulation method incorporating modal representation of random beams, multi-phase screen method and the coordinate transformation to simulate propagation of the COAM matrix of any partially coherent beam propagating in free space or in turbulent medium. The simulation method is thoroughly discussed. As examples, the propagation characteristics of the most representative COAM matrix elements of circular and elliptical Gaussian Schell-model beams in free space and in turbulent atmosphere are studied, and the selection rule is numerically demonstrated.