The transcription factor Runx3 guards cytotoxic CD8+ effector T cells against deviation towards follicular helper T cell lineage.

Activated CD8+ T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8+ TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFß transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program. Ablating Tcf7 in Runx3-deficient CD8+ TEFF cells prevented the upregulation of TFH genes and ameliorated their defective induction of cytotoxic genes. As such, Runx3-mediated Tcf7 repression coordinately enforced acquisition of cytotoxic functions and protected the cytotoxic lineage integrity by preventing TFH-lineage deviation.

Comparison of Cardiac Activated Fibroblast Imaging and Magnetic Resonance Imaging in Patients with COVID-19-Related Myocarditis.

Background: This study aimed to explore the association between cardiac fibroblast activation and cardiac magnetic resonance (CMR) imaging parameters in patients with myocarditis following infection with coronavirus 2019 (COVID-19). Methods: In this prospective study, four patients with COVID-19-related myocarditis underwent 99mTc-labeled-hydrazinonicotinamide-fibroblast activation protein inhibitor-04 (99mTc-HFAPi) single photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging. Segmental 99mTc-HFAPi activity was quantified as the percentage of average segmental myocardial count × global left ventricular target-to-background ratio. T1/T2 values, extracellular volume (ECV), and late gadolinium enhancement (LGE) were analyzed by CMR. The consistency between myocardial 99mTc-HFAPi activity and CMR parameters was explored. Results: In patients with myocarditis, the proportion of segments with abnormal 99mTc-HFAPi activity was significantly higher than in those with abnormal LGE (81.25% vs. 60.93%, p = 0.011), abnormal T2 (81.25% vs. 50.00%, p < 0.001), and abnormal ECV (81.25% vs. 59.38%, p = 0.007); however, they were similar in those with abnormal native T1 (81.25% vs. 73.43%, p = 0.291). Meanwhile, 99mTc-HFAPi imaging exhibited good consistency with native T1 (kappa = 0.69). Conclusions: Increased cardiac 99mTc-HFAPi activity is present in COVID-19-related myocarditis, which is correlated with the native T1 values in CMR.

Auto-focusing femtosecond laser manufacturing system via acoustic emission technology.

Auto-focusing technology in ultrafast laser processing, especially for non-planar structures, holds paramount importance. The existing methodologies predominantly rely on optical mechanisms, thereby being limited by the original system and material reflectivity. This work proposes an approach that utilizes laser-induced sound as a feedback signal for system control, thereby circumventing the need for optical system adjustments and facilitating almost real-time tracking. We established an ultrafast laser processing system augmented by acoustic emission technology, allowing for focus tracking on inclined planes. This system also exhibits the capability to generate diverse microscopic morphologies, including grooves and differently oriented laser-induced periodic surface structures (LIPSS), through the manipulation of the acoustic signal threshold. This method can be easily integrated into existing laser processing systems, offering new capabilities for curved surface processing, microstructure manufacturing, and transparent material processing.

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p-FGFR3 pathway.

BACKGROUND: Partial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin-1 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear. AIMS: Investigate the effects of Thbs1 on bladder remodeling caused by pBOO. METHODS: We established a pBOO model in Sprague-Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin-eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing (RNA-seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT-qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1. RESULTS: Urodynamic results showed that pressure-related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA-seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV-HUC-1), whereas anti-Thbs1 treatment inhibited the production of these cytokines in TGF-ß1-treated SV-HUC-1. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway. CONCLUSIONS: Thbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

Trends by age and sex and projections of disease prevalence from studying hypertensive heart disease in China over the past three decades.

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

MiR398-regulated antioxidants contribute to Bamboo mosaic virus accumulation and symptom manifestation.

Virus infections that cause mosaic or mottling in leaves commonly also induce increased levels of reactive oxygen species (ROS). However, how ROS contributes to symptoms is less well documented. Bamboo mosaic virus (BaMV) causes chlorotic mosaic symptoms in both Brachypodium distachyon and Nicotiana benthamiana. The BaMV △CPN35 mutant with an N-terminal deletion of its coat protein gene exhibits asymptomatic infection independently of virus titer. Histochemical staining of ROS in mock-, BaMV-, and BaMV△CPN35-infected leaves revealed that hydrogen peroxide (H2O2) accumulated solely in BaMV-induced chlorotic spots. Moreover, exogenous H2O2 treatment enhanced yellowish chlorosis in BaMV-infected leaves. Both BaMV and BaMV△CPN35 infection could induce the expression of Cu/Zu superoxide dismutase (CSD) antioxidants at messenger RNA and protein level. However, BaMV triggered the abundant accumulation of full-length NbCSD2 preprotein (prNbCSD2, without transit peptide cleavage), whereas BaMV△CPN35 induced a truncated prNbCSD2. Confocal microscopy showed that majority of NbCSD2-green fluorescent protein (GFP) predominantly localized in the cytosol upon BaMV infection, but BaMV△CPN35 infection tended to cause NbCSD2-GFP to remain in chloroplasts. By 5'-RNA ligase-mediated rapid amplification of cDNA ends, we validated CSDs are the targets of miR398 in vivo. Furthermore, BaMV infection increased the level of miR398, while the level of BaMV titer was regulated positively by miR398 but negatively by CSD2. In contrast, overexpression of cytosolic form NbCSD2, impairing the transport into chloroplasts, greatly enhanced BaMV accumulation. Taken together, our results indicate that induction of miR398 by BaMV infection may facilitate viral titer accumulation, and cytosolic prNbCSD2 induction may contribute to H2O2 accumulation, resulting in the development of BaMV chlorotic symptoms in plants.

Functional significance of myocardial activity at 18F-FAPI PET/CT in hypertrophic cardiomyopathy identified by cardiac magnetic resonance feature-tracking strain analysis.

PURPOSE: This study aimed to evaluate the functional significance of 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) activity in hypertrophic cardiomyopathy (HCM) by comparison with cardiac magnetic resonance feature-tracking (CMR-FT) strain analysis. METHODS: A total of 49 HCM patients were included in this study. Two independent control groups of healthy participants with a matched age and sex to the HCM patients were also enrolled. Left ventricular (LV) 18F-FAPI activity was analyzed for extent (FAPI%) and intensity (maximum target-to-background ratio, TBRmax). The CMR tissue characterization parameters of the LV included late gadolinium enhancement, native T1 value, and extracellular volume fraction. LV strain analysis was performed in radial, circumferential, and longitudinal peak strains (PS). RESULTS: Intense LV myocardial 18F-FAPI uptake was observed in HCM patients, whereas no obvious uptake was detected in healthy participants (median TBRmax, 9.1 vs. 1.2, p < 0.001). The strain parameters of HCM patients, compared with healthy participants, were significantly impaired (mean radial PS, 23.5 vs. 36.0, mean circumferential PS, -14.5 vs. -20.0, and mean longitudinal PS, -9.9 vs. -16.0, all p < 0.001). At segmental levels, there was a moderate correlation between 18F-FAPI activity and strain parameters. The number of positive 18F-FAPI uptake segments (n = 653) was higher than that of hypertrophic segments (n = 190) and positive CMR tissue characterization segments (n = 525) (all p < 0.001). In segments with negative CMR tissue characterization findings, the strain capacity of positive 18F-FAPI uptake segments was lower than that of negative 18F-FAPI uptake segments (median radial PS, 30.5 vs. 36.1, p = 0.026 and median circumferential PS, -18.4 vs. -19.7, p = 0.041). CONCLUSION: 18F-FAPI imaging can partially reflect the potential strain reduction in HCM patients. 18F-FAPI imaging detects more involved myocardium than CMR tissue characterization techniques, and the additionally identified myocardium has impaired strain capacity.

Oriented Plate-like KNbO3 Polycrystals: Topochemical Mesocrystal Conversion and Piezoelectric and Photocatalytic Responses.

KNbO3 (KN) with a perovskite structure is an outstanding representative of lead-free piezoelectric materials, and its mesocrystals have broad application prospects in the fields of catalysis, energy storage, and conversion. However, the formation conditions of KN mesocrystals reported so far are difficult owing to their high aspect ratio and excellent preferred orientation. In this study, the solvothermal process was used successfully to prepare the flake-like potassium salt of Lindquist hexaniobate (K8Nb6O19·10H2O). Subsequently, the precursor niobate was calcined to prepare two-dimensional (2D) plate-like KN mesocrystals. The formation mechanism of the plate-like KN mesocrystals is further revealed from a paired topochemical mesocrystal conversion of K8Nb6O19·10H2O niobate. Finally, the microscopic piezoelectric and photocatalytic responses of the obtained plate-like KN mesocrystals were investigated. The high piezoelectric coefficient of plate-like KN mesocrystals implies that excellent charge separation promotes the photocatalytic performance of rhodamine B (RhB). This study provides a strategy for the efficient application of 2D oriented materials in the field of piezoelectricity and photocatalysis.