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Abstract Background Coronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions. Objective We aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA). Methods We conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded. Results The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up. Conclusion CT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients. Graphical abstract

IntroductionIn atrial fibrillation (AF) ablation, fluoroscopy has been a standard tool for catheter guidance. However, the combination of electroanatomic mapping systems (EAMs) and intracardiac echocardiography (ICE) now allows for minimal or zero-fluoroscopy procedures. Concurrently, high-power short-duration (HPSD) ablation has emerged as a promising technique, offering enhanced resistive heating while reducing conductive heating. This approach potentially improves both safety and efficacy. Despite these advancements, there is a lack of comprehensive clinical data on the safety and effectiveness of HPSD ablation when used in conjunction with ICE-guided zero-fluoroscopy procedures.ObjectiveTo compare two different ablation strategies—high-power short-duration (HPSD) and low-power long-duration (LPLD)—both utilizing intracardiac echocardiography (ICE)-guided zero-fluoroscopy in the context of atrial fibrillation (AF) ablation.MethodsThis retrospective study included 173 consecutive patients with AF who underwent ICE-guided zero-fluoroscopy ablation. Patients were divided into two groups: HPSD and LPLD. All procedures were conducted using an EAM system with ICE guidance. Both groups underwent routine pulmonary vein isolation (PVI), with additional linear ablations performed for persistent AF when necessary. We compared treatment outcomes and the incidence of complications between the two groups.ResultsAll procedures were successfully completed under ICE-guided zero-fluoroscopy, establishing a feasible and reliable workflow. The procedure and ablation times were significantly shorter in the HPSD group compared to the LPLD group. At one-year follow-up, sinus rhythm was maintained in 77 patients in the HPSD group and 74 patients in the LPLD group, with no significant difference between the two group. Postoperative complications occurred in 5 patients in the HPSD group and 3 patients in the LPLD group. Importantly, there were no major adverse cardiac and cerebrovascular events (MACCE) in either group.ConclusionA zero-fluoroscopy workflow utilizing an EAM system combined with ICE appears to be both feasible and safe for ablation in AF patients. In patients undergoing ICE-guided zero-fluoroscopy ablation, the HPSD strategy is comparable to LPLD ablation in effectiveness while offering the benefit of shorter procedure and ablation times.

Background: The need for primary percutaneous coronary intervention (PCI) and staged PCI strategy for ST-segment elevation myocardial infarction (STEMI) with multivessel coronary disease is well documented. This study aimed to evaluate the efficiency, safety, and cost benefit of quantitative flow ratio (QFR)-guided staged PCI in patients with STEMI. Methods: We conducted a retrospective study involving 2256 patients meeting STEMI criteria having at least one lesion (≥50 %) in non-infarct-related (NIR) arteries. These patients had undergone primary PCI for infarct-related (IR) arteries and staged PCI for NIR arteries. Patients were categorized into two groups based on the strategy guided either by QFR or quantitative coronary angiography (QCA) as determined by the clinicians during primary PCI in real-world. For patients guided by QFR, a threshold of ≤0.80 serves as the cut-off value for determining the need for PCI. We recorded the demographics, clinical data, and QFR values of none-infarct-related arteries. The efficiency, safety, and cost benefit of the QFR-guided staged PCI were evaluated. Results: The QCA-guided group had a higher rate of Killip II. In the QFR-guided group, there was a higher proportion of left anterior descending coronary artery lesions in infarct-related arteries. The mean QFR value of non-infarct-related (NIR) arteries remained consistent at 0.83 across both groups, irrespective of whether the measurement was taken during the primary PCI or the staged PCI phase. Among patients with QFR ≤0.8, the QFR values during staged PCI were significantly higher than that during primary PCI, with a significantly greater increase compared to patients with QFR >0.8. The proportion of staged PCI, number of stents per patient, and cost of staged PCI per patient were significantly lower in the QFR-guided group compared to the QCA-guided group. In the long-term follow-up period, there were no statistically significant differences between the two groups in terms of major adverse cardiac events and clinic visits, except for target vessel revascularization. Conclusions: QFR resulted in a reduction in the proportion of STEMI patients with multivessel coronary disease undergoing invasive coronary angiography and staged PCI. Furthermore, it decreased the incidence of target vessel revascularization (TVR) and medical costs, without increasing major adverse cardiovascular events. Our future work will focus on large multi-center perspective studies for the feasibility of QFR guided staged PCI in patients with STEMI.

HfC-SiC modified C/C composites containing in situ formed Si-HfC-HfSi2 ablation resistant layer and SiC oxidation resistant layer were successfully prepared by reactive melt infiltration (RMI) combined with gaseous silicon infiltration (GSI). A comparative study was conducted on the anti-oxidation and anti-ablation performance of the C/C-HfC-SiC composites with GSI (noted as RG-CHS) and without GSI (noted as R-CHS). After oxidation at 1,500 °C for 200 min, the oxide film of RG-CHS remained intact. The mass and linear ablation rates decreased from 1.31 mg/s and 7.36 μm/s to 0.12 mg/s and −0.22 μm/s after GSI process, respectively. The introduction of low melting point phases and reducing surface defects can improve the high temperature oxidation resistance and plasma ablation resistance of the composites.

Abstract Background Polycystic ovary syndrome (PCOS) is a gynecological endocrine disease and could be considered a metabolic disease because it is often accompanied by obesity and insulin resistance. Brown adipose tissue (BAT) transplantation has been shown to be effective in treating PCOS rats. Results The study demonstrated that BAT successfully recovered the reproductive and metabolic phenotype of PCOS rats. The disorder estrous cycle, abnormal hyperglycemia and the expression of liver factors were improved. Differentially expressed metabolites were analyzed, among them, arachidonic acid may play a role in inhibiting cell proliferation, enhancing oxidative stress reaction, promoting estrogen expression, and reducing progesterone level in KGN cells. Conclusion Our findings suggest that BAT transplantation may be a therapeutic strategy for PCOS by changing the expression of some cytokines and metabolites. Differentially expressed metabolites might be crucially important for the pathogenesis of PCOS.

AbstractBackground Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common subtype of HLH with heterogeneous clinical presentations from self-limited to death, of which adults are worse than children.Objective To establish predictors of mortality risk in adult EBV-HLH patients for timely and appropriate treatment.Methods Patients with confirmed EBV-HLH admitted to Beijing Friendship Hospital from January 2015 to December 2019 were enrolled and statistical analysis of their laboratory test results was performed.Results Among 246 adult patients with EBV-HLH, the deceased were older (p 18,000 pg/mL or only eGFR < 90 mL/min/1.73m2), and IH2+ (i.e. the rest), respectively. In patients with the HScore ≥ 169 or meeting HLH-04, those meeting IH2+ had significantly worse prognoses than those who met IH1+ or IH- (p

This study aimed to investigate the effects of different dietary concentrate-to-forage ratios on slaughter performance, meat quality, rumen fermentation, rumen microbiota and fecal microbiota in Tibetan sheep. A total of sixty male Tibetan sheep were equally allocated into three dietary groups based on concentrate-to-forage ratios, i.e., 30:70 (C30), 50:50 (C50), and 70:30 (C70). Compared with the C30 group, sheep fed the C70 diet resulted in a higher (p < 0.05) slaughter live weight (SLW), hot carcass weight (HCW), dressing percentage (DP), eye muscle area, average daily gain (ADG), and ruminal total volatile fatty acids concentration and propionate molar proportion and lower (p < 0.05) shear force and cooking loss of meat, and ruminal acetate molar proportion and acetate:propionate ratio. Sheep in the C50 group exhibited a higher (p < 0.05) SLW, HCW, ADG, and ruminal propionate molar proportion and lower (p < 0.05) shear force and cooking loss of meat, and ruminal acetate molar proportion and acetate: propionate ratio compared with the C30 group. In rumen fluid, the relative abundance of Butyrivibrio was lower (p = 0.031) in the C30 group, and that of Ruminococcus was higher (p = 0.003) in the C70 group compared with the C50 group. In feces, genus Monoglobus and UCG_002 were the most abundant in the C30 group (p < 0.05), and the relative abundance of Prevotella was significantly higher in the C70 group than in other groups (p = 0.013). Correlation analysis revealed possible links between slaughter performance and meat quality and altered microbiota composition in the rumen and feces of Tibetan sheep. Overall, feeding a C70 diet resulted in superior carcass characteristics and meat quality in Tibetan sheep, thus laying a theoretical basis for the application of short-term remote feeding during the cold season.

ObjectiveTo test the psychometric properties of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry (C-BRIAN) in a group of young adults with and without depressive symptoms.MethodsThree hundred and seventy-eight university students were recruited as participants. Based on the scores from Center for Epidemiological Survey Depression Scale (CES-D), students were divided into the depressed group and healthy group. Explorative factor analysis was applied to assess the construct validity of the C-BRIAN. The Pittsburgh Sleep Quality Index (PSQI) and CES-D were compared with the C-BRIAN to test the convergent validity. The internal consistency of the C-BRIAN was also examined.ResultsThree factors were extracted (activities, eating patterns, and sleep factors) explaining 63.9% of the total variance. The internal consistencies were very good with a coefficient of 0.94 (overall) and 0.89–0.91 for three factors. The domains of activities, eating patterns, and sleep were moderately correlated with PSQI (r=0.579) and CES-D (r=0.559) (ps

Abstract Over the last decade, the possibility of realizing topological superconductivity (TSC) has generated much excitement. TSC can be created in electronic systems where the topological and superconducting orders coexist, motivating the continued exploration of candidate material platforms to this end. Here, we use molecular beam epitaxy (MBE) to synthesize heterostructures that host emergent interfacial superconductivity when a non-superconducting antiferromagnet (FeTe) is interfaced with a topological insulator (TI) (Bi, Sb)2Te3. By performing in-vacuo angle-resolved photoemission spectroscopy (ARPES) and ex-situ electrical transport measurements, we find that the superconducting transition temperature and the upper critical magnetic field are suppressed when the chemical potential approaches the Dirac point. We provide evidence to show that the observed interfacial superconductivity and its chemical potential dependence is the result of the competition between the Ruderman-Kittel-Kasuya-Yosida-type ferromagnetic coupling mediated by Dirac surface states and antiferromagnetic exchange couplings that generate the bicollinear antiferromagnetic order in the FeTe layer.

Abstract An axion insulator is a three-dimensional (3D) topological insulator (TI), in which the bulk maintains the time-reversal symmetry or inversion symmetry but the surface states are gapped by surface magnetization. The axion insulator state has been observed in molecular beam epitaxy (MBE)-grown magnetically doped TI sandwiches and exfoliated intrinsic magnetic TI MnBi2Te4 flakes with an even number layer. All these samples have a thickness of ~ 10 nm, near the 2D-to-3D boundary. The coupling between the top and bottom surface states in thin samples may hinder the observation of quantized topological magnetoelectric response. Here, we employ MBE to synthesize magnetic TI sandwich heterostructures and find that the axion insulator state persists in a 3D sample with a thickness of ~ 106 nm. Our transport results show that the axion insulator state starts to emerge when the thickness of the middle undoped TI layer is greater than ~ 3 nm. The 3D hundred-nanometer-thick axion insulator provides a promising platform for the exploration of the topological magnetoelectric effect and other emergent magnetic topological states, such as the high-order TI phase.

Objective: Benign childhood epilepsy with centrotemporal spikes (BECTS) affects brain network hierarchy and cognitive function; however, it remains unclear how hierarchical change affects cognition in patients with BECTS. A major aim of this study was to examine changes in the macro-network function hierarchy in BECTS and its potential contribution to cognitive function. Methods: Overall, the study included 50 children with BECTS and 69 healthy controls. Connectome gradient analysis was used to determine the brain network hierarchy of each group. By comparing gradient scores at each voxel level and network between groups, we assessed changes in whole-brain voxel-level and network hierarchy. Functional connectivity was used to detect the functional reorganization of epilepsy caused by these abnormal brain regions based on these aberrant gradients. Lastly, we explored the relationships between the change gradient and functional connectivity values and clinical variables and further predicted the cognitive function associated with BECTS gradient changes. Results: In children with BECTS, the gradient was extended at different network and voxel levels. The gradient scores frontoparietal network was increased in the principal gradient of patients with BECTS. The left precentral gyrus (PCG) and right angular gyrus gradient scores were significantly increased in the principal gradient of children with BECTS. Moreover, in regions of the brain with abnormal principal gradients, functional connectivity was disrupted. The left PCG gradient score of children with BECTS was correlated with the verbal intelligence quotient (VIQ), and the disruption of functional connectivity in brain regions with abnormal principal gradients was closely related to cognitive function. VIQ was significantly predicted by the principal gradient map of patients. Significance: The results indicate connectome gradient disruption in children with BECTS and its relationship to cognitive function, thereby increasing our understanding of the functional connectome hierarchy and providing potential biomarkers for cognitive function of children with BECTS.

Abstract Inter-site interaction in densely populated single-atom catalysts has been demonstrated to have a crucial role in regulating the electronic structure of metal atoms, and consequently their catalytic performances. We herein report a general and facile strategy for the synthesis of several densely populated single-atom catalysts. Taking cobalt as an example, we further produce a series of Co single-atom catalysts with varying loadings to investigate the influence of density on regulating the electronic structure and catalytic performance in alkene epoxidation with O2. Interestingly, the turnover frequency and mass-specific activity are significantly enhanced by 10 times and 30 times with increasing Co loading from 5.4 wt% to 21.2 wt% in trans-stilbene epoxidation, respectively. Further theoretical studies reveal that the electronic structure of densely populated Co atoms is altered through charge redistribution, resulting in less Bader charger and higher d-band center, which are demonstrated to be more beneficial for the activation of O2 and trans-stilbene. The present study demonstrates a new finding about the site interaction in densely populated single-atom catalysts, shedding insight on how density affects the electronic structure and catalytic performance for alkene epoxidation.

Quantum anomalous Hall junctions show great promise for advancing next-generation electronic circuits. Here, the authors demonstrate a scalable method for synthesizing heterostructures of magnetic topological insulators with regions of distinct Chern numbers and characterize the chiral interface modes that emerge at the interface.

The nonlinear Hall effect (NLHE) results in a second-harmonic transverse voltage in response to alternating longitudinal current in zero magnetic field and has so far only been observed at low temperatures in bulk materials. Here, the authors observe bulk NLHE at room temperature in the Dirac material BaMnSb2, which will provide a large photocurrent for applications in THz detection.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome with a high mortality rate. There is no biomarker to predict the early therapeutic response. Objective: Our study explores the significance of serum ferritin in predicting the response of induction therapy. Methods: We retrospectively analyzed the clinical data of 102 adult patients with HLH admitted to our hospital. These patients received HLH-94 regimen for induction therapy. The patients were divided into remission group and non-remission group according to the response of induction therapy. Results: Ferritin values between 1–4 weeks post induction were predictive of remission (p

Background and objective: As a partial positive allosteric modulator of the gamma-aminobutyric acid A (GABAA) receptor, dimdazenil was used for the treatment of insomnia with the potential to alleviate associated side effects compared to full agonists. The objective of this trial is to assess the safety, tolerability, food effect and pharmacokinetics following single and multiple doses of dimdazenil in Chinese healthy subjects.Methods: In this phase 1 trial, 36 healthy subjects aged ≥18 years were assigned to receive a single dose of 1.5, 2.5, or 5 mg dimdazenil, with each dose cohort consisting of 12 subjects, and 14 subjects were assigned to receive a multiple 2.5 mg daily dose of dimdazenil for 5 days. Safety, tolerability, and pharmacokinetic characteristics were evaluated.Results: Of the 50 subjects enrolled and 49 completed the trial, the incidences of treatment-emergent adverse events (AEs) in the single-dose groups of 1.5, 2.5, and 5 mg were 16.7%, 58.3% and 66.7% respectively, while 61.5% in the multiple-dose group. There were no serious AEs, deaths, AEs leading to discontinuation or AEs of requiring clinical intervention in any treatment groups. The most treatment-emergent AEs were dizziness (n = 4, 8.2%), hyperuricemia (n = 2, 6.1%), upper respiratory tract infection (n = 2, 6.1%), diastolic blood pressure decreased (n = 2, 6.1%), blood TG increased (n = 2, 6.1%) and RBC urine positive (n = 2, 6.1%). All AEs were mild-to-moderate and transient, and no severe AEs were documented in any study phase. The PK profile of dimdazenil and its active metabolite Ro46-1927 was linear across 1.5–5 mg oral doses in humans. The median Tmax for dimdazenil was in the range of 0.5–1.5 h, and the apparent terminal t1/2z ranged from 3.50 to 4.32 h. Taking Dimdazenil with food may delay Tmax and decrease Cmax, without affecting the total exposure (AUC). No relevant accumulations of dimdazenil and Ro 46–1927 were observed in multiple-dose group.Conclusion: Dimdazenil was generally well tolerated in healthy Chinese subjects after single and 5 days-multiple dosing. The pharmacokinetic properties of dimdazenil are compatible with a drug for the treatment of insomnia.Clinical Trial Registration: chinadrugtrials.org.cn, identifier CTR20201978

Urban renewal planning and development are vital for enhancing the living quality of city residents. However, such improvement activities are often expensive, time-consuming, and in need of standardization. The convergence of remote sensing technologies, social big data, and artificial intelligence solutions has created unprecedented opportunities for comprehensive digital planning and analysis in urban renewal development and management. However, fast interdisciplinary development imposes some challenges because the data collected and the solutions built are defined piece by piece and require further fusion and integration of knowledge, evaluation standards, systematic analyses, and new methodologies. To address these challenges, we propose a municipal and urban renewal development index (MUDI) system with data modeling and mathematical analysis models. The MUDI system is applied and studied in three circumstances: (1) at regional level, 337 cities are selected in China to demonstrate the MUDI system’s comparable analysis capabilities on a large scale across cities; (2) at city level, 285 residential communities are selected in Xiamen to demonstrate the use of remote sensing data as key MUDIs for a temporal urban land change analysis; and (3) at the level of residential neighborhoods’ urban renewal practices, Xiamen’s Yingping District is selected to demonstrate the MUDI system’s project management capabilities. We find that the MUDI system is highly effective in municipal and urban data model building through the abstraction and summation of grid-based satellite and social big data. Secondly, the MUDI system enables comprehension of the high dimensionality and complexity of multisource datasets for municipal and urban renewal development. Thirdly, the system is applied to enable the use of the newly developed UMAP algorithm, a model based on Riemannian geometry and algebraic topology, and the carrying out of a principal component analysis for the key dimensions and an index correlation analysis. Fourthly, various artificial intelligence-driven algorithms can be developed for urban renewal analyses based on the MUDIs. The MUDI system is a new and effective method for urban renewal planning and management that can be flexibly extended and applied to various cities and urban districts.

Abstract This study examined the structural brain differences across individuals of different BD stages and the risks of developing bipolar disorder (BD) associated with these brain differences. A total of 221 participants who were recruited from the Guangzhou Brain Hospital and the community were categorized into four groups: NC (healthy control) (N = 77), high risk (HR) (N = 42), ultra-high risk (UHR) (N = 38), and bipolar disorder (BD) (N = 64) based on a list of criteria. Their demographics, clinical characteristics, and diffusion magnetic resonance imaging (dMRI) data were collected. ANCOVA results showed that the HR group had significantly reduced mean diffusivity (MD) (p = 0.043) and radial diffusivity (RD) (p = 0.039) of the left portico-ponto-cerebellar tracts when compared with the BD group. Moreover, logistic regression results showed that the specific diffusivity measures of cerebellar tracts (e.g., cortico-ponto-cerebellar tract), particularly the RD and MD revealed differences between groups at different BD stages after controlling for the covariates. The findings suggested that specific diffusivity (RD and MD) of cerebellar tracts (e.g., cortico-ponto-cerebellar tract) revealed differences between groups at different BD stages which is helpful in detecting the trajectory changes in BD syndromes in the early stages of BD, particularly when the BD syndromes start from HR stage.

ObjectivesTo describe the clinical characteristics and outcomes of adult macrophage activation syndrome (MAS) patients and to provide experience for the treatment.MethodsAdult patients with MAS admitted to Beijing Friendship Hospital from December 2014 to September 2021 were enrolled in this study. Clinical data of patients were collected and analyzed.ResultsA total of 118 adult MAS patients entered this study. MAS was the first manifestation in 43 (36.4%) patients, while 75 (63.6%) developed MAS after the diagnosis of autoimmune disease (AID) with a median diagnostic interval of 2 (0.5–359) months. Eighty-two patients were initially treated with glucocorticoid-based regimen; the overall response (OR) rate at the 2-week posttreatment was 37.8%. Forty-five patients switched to etoposide-based regimen, and the OR rate was 84.4%. Thirty-six patients were initially treated with etoposide-based regimen, and the OR rate at the 2-week posttreatment was 80.6%. Serum IL-18 (P = 0.021), IFN-γ (P = 0.013), IP-10 (P = 0.001), IL-10 (P = 0.041), IL-1RA (P < 0.001), and TNF-α (P = 0.020) levels of patients were significantly decreased in the remission phase than in the active phase. Levels of SDF-1α (P = 0.018) and IL-7 (P = 0.022) were higher in refractory patients, while the GRO-α level had a strong tendency toward statistical significance (P = 0.050). The probability of overall survival (OS) at 3, 6, and 36 months after HLH diagnosis were 89.8%, 89.0%, and 87.9%, retrospectively. The active MAS status at the 2-week post initial treatment [P = 0.009, HR = 15.281, 95% CI, (0.1.972, 118.430)] and baseline neutrophil count (Neu)

Abstract Cell death and immune response are at the core of life. In past decades, the endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in the production of type I interferons (IFNs) and pro-inflammatory cytokines in response to DNA derived from invading microbial pathogens or damaged hosts by activating multiple transcription factors. In addition to this well-known function in infection, inflammation, and immunity, emerging evidence suggests that the STING1-dependent signaling network is implicated in health and disease by regulating autophagic degradation or various cell death modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic cell death, and immunogenic cell death [ICD]). Here, we outline the latest advances in our understanding of the regulating mechanisms and signaling pathways of STING1 in autophagy and cell death, which may shed light on new targets for therapeutic interventions.

BackgroundIntracerebral hemorrhage (ICH) is the devastating subtype of stroke with cardiovascular complications, resulting in high rates of mortality and morbidity with the release of inflammatory factors. Previous studies have demonstrated that activation of α7nAChR can reduce immune and inflammation-related diseases by triggering the cholinergic anti-inflammatory pathway (CAIP). α7nAChR mediates protection from nervous system inflammation through AMPK-mTOR-p70S6K-associated autophagy. Therefore, the purpose of this study is to explore whether the activation of α7nAChR improves cerebral and cardiac dysfunction after ICH through autophagy.MethodsMale C57BL/6 mice were randomly divided into five groups (1): Control + saline (2), ICH+ saline (3), ICH + PNU-282987 (4), ICH+ PNU-282987 + MLA (5), ICH + PNU-282987 + 3-MA. The neurological function was evaluated at multiple time points. Brain water content was measured at 3 days after ICH to assess the severity of brain edema. PCR, immunofluorescence staining, and Western Blot were performed at 7 days after ICH to detect inflammation and autophagy. Picro-Sirius Red staining was measured at 30 days after ICH to evaluate myocardial fibrosis, echocardiography was performed at 3 and 30 days to measure cardiac function.ResultsOur results indicated that the PNU-282987 reduced inflammatory factors (MCP-1, IL-1β, MMP-9, TNF-α, HMGB1, TLR2), promoted the polarization of macrophage/microglia into anti-inflammatory subtypes(CD206), repaired blood-brain barrier injury (ZO-1, Claudin-5, Occludin), alleviated acute brain edema and then recovered neurological dysfunction. Echocardiography and PSR indicated that activation of α7nAChR ameliorated cardiac dysfunction. Western Blot showed that activation of α7nAChR increased autophagy protein (LC3, Beclin) and decreased P62. It demonstrated that the activation of α7nAChR promotes autophagy and then recovers brain and heart function after ICH.ConclusionsIn conclusion, PNU-282987 promoted the cerebral and cardiac functional outcomes after ICH in mice through activated α7nAChR, which may be attributable to promoting autophagy and then reducing inflammatory reactions after ICH.

Background: Most acute coronary syndromes occur due to coronary thrombosis caused by plaque rupture (PR) and plaque erosion (PE). Precise in vivo differentiation between PR and PE is challenging for intravascular imaging. This study is the first to determine the diagnostic performance of the novel 60 MHz high-definition intravascular ultrasound (HD-IVUS) for differentiating atherosclerotic plaque morphology influenced by local hemodynamic flow in rabbits. This study evaluated the diagnostic performance of 60 MHz HD-IVUS in identifying thrombosis in rabbits. Methods: We established 60 rabbit models of atherosclerosis with left common carotid artery (LCCA) stenosis and 30 FeCl3-induced LCCA thrombosis. Intravascular imaging was assessed with 60 MHz HD-IVUS and fourier-domain optical coherence tomography (FD-OCT). The present study investigated the diagnostic accuracy of 60 MHz HD-IVUS for PR and PE, as well as thrombosis, using OCT-diagnosis as a standard reference. Results: 60 MHz HD-IVUS for identifying atherosclerotic plaque morphology using plaque cavity and minor intimal irregularities showed high sensitivity and specificity; 92.0 and 90.0% for identifying OCT-defined PR, and 80.0 and 70.0% for OCT-defined PE, respectively. In a rabbit thrombus model, 60 MHz HD-IVUS showed high sensitivity (88.0%) and specificity (80.0%) in identifying OCT-defined thrombosis. Conclusions: 60 MHz HD-IVUS can accurately identify PR and thrombosis. Further studies should confirm the clinical value of this novel technique in PE diagnosis.

Abstract Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Street vitality plays an important role in improving residents’ quality of life and advancing urban development. However, traditional research methods pay minimal attention to pedestrians’ behavior, ignoring crowd preferences vis-à-vis the street-space. Utilizing the historic block of Shapowei in Xiamen as an illustrative example, this manuscript systematically examines the impact of this historic block’s built environment on street vitality. Using multimode analysis technologies including Global Positioning System (GPS) and Geographic Information System (GIS) software helps analyze time and space data on pedestrians; evaluates the space perception of the residents; assesses the street’s visual appeal, as well as the appeal of its commercial activities; identifies the environmental elements and rules of the high-vitality street space. Therefore, it puts forward suggestions for street planning and architectural design. This article constructs a street vitality evaluation system based on pedestrians’ time and space data, providing a new perspective for the research and design of the historical block space. In conclusion, the research suggests that the spatial change of the street, the openness of the building facade, and the spatial distribution of the shops have different impacts on pedestrians’ activities when the built-up environment is a concern.

AimsAcute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).MethodsThis retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.ResultsOxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.ConclusionsLevosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.

Stimulator of interferon response cGAMP interactor 1 (STING1), also known as TMEM173, is an immune adaptor protein that governs signal crosstalk that is implicated in many physiological and pathological processes. Although it has been established that STING1 traffics from the endoplasmic reticulum (ER) to Golgi apparatus (Golgi) upon DNA-triggered activation, emerging evidence reveals that STING1 can be transported to different organelles, which dictate its immune-dependent (e.g., the production of type I interferons and pro-inflammatory cytokines) and -independent (e.g., the activation of autophagy and cell death) functions. In this brief review, we outline the roles of STING1 in different organelles (including the ER, ER-Golgi intermediate compartment, Golgi, mitochondria, endosomes, lysosomes, and nucleus) and discuss the potential relevance of these roles to diseases and pharmacological interventions.

Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. Portulaca oleracea L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, via integrating bioinformatics analysis and experimental pharmacology both in vitro and in vivo. The phenotypes and mechanisms of POL were carefully investigated by performing a set of in vivo and in vitro experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including FASN, CPT1a, SERBP1c, ACC1, and SCD1. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-α, IL-6, and IL-1β. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH via down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.

BackgroundMalignancies, especially lymphoma, are a common cause of adult secondary HLH and an independent risk factor for the prognosis of HLH patients.MethodsPatients with lymphoma alone or concurrent lymphoma-associated phagocytic syndrome (LAHS) admitted to Beijing Friendship Hospital from January 2016 to December 2020 were enrolled in this study.FindingsThere were 348 lymphoma patients, 104 concurrent with LAHS. The pathological type of lymphoma without LAHS was dominated by B-cell lymphoma, while those with LAHS were T/NK-cell lymphoma predominantly (p < 0.001). Superficial lymph node enlargement was more significant in patients with B-LAHS (p = 0.006), while patients with T/NK-LAHS had lower neutrophil counts (p = 0.005), lower fibrinogen levels (p < 0.001), higher transaminase levels, and more co-infection with EBV (p < 0.001). B-LAHS had significantly higher IL-10 levels than with T/NK-LAHS (p = 0.006), and NK/T-LAHS had significantly higher IP-10 levels than other T-LAHS (p = 0.008). Age, platelet count, IPI, history of NK/T lymphoma, and no remission of HLH were independent risk factors for prognosis in patients with non-Hodgkin lymphoma-associated phagocytic syndrome (NHL-LAHS), and a prognostic risk score model for NHL-LAHS was developed.ConclusionLAHS is a life-threatening disease with a poor prognosis. The prognostic risk score model for NHL-LAHS with a good fit and validation for the test has value for clinical application.

Hyperglycemia-induced endothelial cell senescence has been widely reported to be involved in the pathogenesis of type 2 diabetes mellitus‒accelerated atherosclerosis. Thus, understanding the underlying mechanisms and identifying potential therapeutic targets for endothelial cell senescence are valuable for attenuating atherosclerosis progression. C1q/tumor necrosis factor-related protein 9 (CTRP9), an emerging potential cardiokine, exerts a significant protective effect with respect to atherosclerosis, particularly in endothelial cells. However, the exact mechanism by which CTRP9 prevents endothelial cells from hyperglycemia-induced senescence remains unclear. This study aimed to investigate the effects of CTRP9 on hyperglycemia-induced endothelial cell senescence and atherosclerotic plaque formation in diabetic apolipoprotein E knockout (ApoE KO) mice. Human umbilical vein endothelial cells (HUVECs) were cultured in normal glucose (5.5 mM) and high glucose (40 mM) with or without recombinant human CTRP9 protein (3 μg/ml) for 48 h. Purified lentiviruses overexpressing CTRP9 (Lv-CTRP9) and control vectors containing green fluorescent protein (Lv-GFP) were injected via the tail vein into streptozotocin-induced diabetic ApoE KO mice. Results revealed that exposure of HUVECs to HG significantly increased the expression of Krüppel-like factor 4 (KLF4) and cyclin-dependent kinase inhibitor p21 (p21) and decreased that of telomerase reverse transcriptase (TERT). Treatment with recombinant human CTRP9 protein protected HUVECs from HG-induced premature senescence and dysfunction. CTRP9 promoted the phosphorylation of AMP-activated kinase (AMPK), attenuated the expression of KLF4 and p21 induced by HG, and increased the expression of TERT in HUVECs. Furthermore, in the background of AMPKα knockdown or KLF4 activation, the protective effects of CTRP9 were abolished. In-vivo experiments showed that the overexpression of CTRP9 inhibited vascular senescence and reduced atherosclerotic plaque formation in ApoE KO mice with diabetes. In conclusion, we demonstrate that KLF4 upregulation plays a crucial role in HG-induced endothelial senescence. This anti-atherosclerotic effect of CTRP9 may be partly attributed to the inhibition of HG-induced endothelial senescence through an AMPKα/KLF4-dependent mechanism, suggesting that CTRP9 could benefit further therapeutic approaches for type 2 diabetes mellitus‒accelerated atherosclerosis.

Introduction: It has been reported that sex has well-established relationships with the prevalence of coronary artery disease (CAD) and the major adverse cardiovascular events. Compared with men, the difference of coronary artery and myocardial characteristics in women has effects on anatomical and functional evaluations. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in acute myocardial infarction patients is unknown. This study aimed to evaluate the sex differences in the non-infarct-related artery (NIRA)-based QFR in patients with ST-elevation myocardial infarction (STEMI).Methods: In this study, 353 patients with STEMI who underwent angiographic cQFR assessment and interventional therapy were included. According to contrast-flow QFR (cQFR) standard operating procedures: reliable software was used to modeling the hyperemic flow velocity derived from coronary angiography in the absence of pharmacologically induced hyperemia. 353 patients were divided into two groups according to sex. A cQFR ≤0.80 was considered hemodynamically significant, whereas invasive coronary angiography (ICA) luminal stenosis ≥50% was considered obstructive. Demographics, clinical data, NIRA-related anatomy, and functional cQFR values were recorded. Clinical outcomes included the NIRA reclassification rate between men and women, according to the ICA and cQFR assessments.Results: Women were older and had a higher body mass index (BMI) than men. The levels of diastolic blood pressure, troponin I, peak creatine kinase-MB, low-density lipoprotein cholesterol, N terminal pro B-type natriuretic peptide, stent diameter, and current smoking rate were found to be significantly lower in the female group than in the male group. Women had a lower likelihood of a positive cQFR ≤0.80 for the same degree of stenosis and a lower rate of NIRA revascularization. Independent predictors of positive cQFR included male sex and diameter stenosis (DS) >70%.Conclusions: cQFR values differ between the sexes, as women have a higher cQFR value for the same degree of stenosis. The findings suggest that QFR variations by sex require specific interpretation, as these differences may affect therapeutic decision-making and clinical outcomes.

Background: Acute systolic heart failure (ASHF) is one of the most serious complications of the acute coronary syndrome (ACS), and increases the likelihood of adverse clinical outcomes. It remains unclear whether the use of non-invasive ventilation (NIV) could improve symptoms and reduce mortality in patients with ASHF derived from ACS. Methods: Data on biological, clinical, and demographic factors, as well as therapy data, were collected from patients with ASHF in the cardiac department. A total of 1257 ACS patients with ASHF were included in the study. Patients were divided into two groups. The control group received standard oxygen therapy. The comparison group consisted of those who underwent NIV as part of their immediate care. During hospitalization and at follow-up, information on both groups was systematically compared. Results: In comparison with the control group, mean 24-hour urine output was found to be significantly higher in the NIV group. A significant reduction in the duration of symptoms was observed among patients in the NIV group from the time of admission until relief of dyspnea. Heart rate, C-reactive protein, estimated glomerular filtration rate, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was also improved, compared with those in the control group. The NIV group was found to have a higher survival rate. NIV was independently related to all-cause mortality in 1-year follow-up (hazard ratio, 0.674; p = 0.045). Conclusions: Our study shows that NIV, as compared with standard oxygen therapy, has a beneficial impact on heart rate, metabolic balance, and relief of dyspnea in ACS patients with ASHF which results in reduced intubation rate, duration of in-hospital stay, and 1-year mortality.

Background: Electrocautery and staplers are regarded as the two most common surgical instruments for dissecting the intersegmental plane in segmentectomy. We performed a meta-analysis to compare electrocautery and staplers in terms of their safety and effects.Methods: A systematic search strategy was performed using PubMed, and the retrieval time was up to April 1, 2020. Odds ratio (OR) and mean differences (MDs) with 95% CI were applied to determine the effectiveness of dichotomous or continuous variables, respectively.Results: Six studies including 385 patients were included. The electrocautery had a higher incidence rate of postoperative complication [OR= 1.92, 95% CI (1.12, 3.28), P = 0.02)] and air leak [OR: 3.91, 95% CI (1.64, 9.35), P = 0.002)]. No significant difference was found in the comparison of surgery time, blood loss, and duration of tube days or hospitality days.Conclusions: Our study indicated that patients under segmentectomy were associated with better safety by using stapler than electrocautery in the reduction of postoperative complications.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been reported to have negative psychological impact on mental health. Nonetheless, there are few studies investigating the impacts on pregnant women. This study investigated the psychological impact of COVID-19 pandemic on pregnant women, and the associated risk factors that moderated this impact.Methods and Materials: A total of 2,798 pregnant participants were recruited from the Guangzhou Women and Children's Medical Center. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI) were used to assess depression, generalized anxiety disorder and insomnia, respectively, during and before the COVID-19 pandemic. The Impact of Event Scale-Revised (IES-R) was used to assess psychological stress during the COVID-19 pandemic.Results: During the COVID-19 pandemic, over one third of pregnant participants reported mild depression, around 20% experienced mild generalized anxiety, about one third reported problems with sleeping, and more than 15% felt mild psychological stress. The occurrence of psychological problems was significantly higher during the COVID-19 pandemic when compared to before the outbreak. The previously described pattern that pregnant women in the first trimester are more likely to report depression, and those in the third trimester are more likely to report insomnia and psychological stress, was also recognized in our study population. Mental health issues existing before the outbreak were risk factors, while family support was a protective factor in the occurrence of the measured mental health problems during the COVID-19 pandemic.Conclusion: Our data suggest pregnant women's mental health is inevitably affected during the COVID-19 pandemic. Pregnant women in the first and third trimester and those who experienced mental issues before the outbreak may be particularly affected.

Abstract Background Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. Methods Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. Results We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. Conclusions Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.

Fractional quantum Hall states in 2D electron gases arise due to strong electron-electron interactions, which makes a general theoretical understanding difficult. Fu et al. present data showing the ν = 5/3 quantum Hall state has a 3/2 plateau in the diagonal resistance that has not been captured by existing models.

Male sterility is an important agronomic trait for hybrid vigor utilization and hybrid seed production, but its underlying mechanisms remain to be uncovered. Here, we investigated the mechanisms of male sterility in peach using a combined cytology, physiology, and molecular approach. Cytological features of male sterility include deformed microspores and tapetum cells along with absence of pollen grains. Microspores had smaller nucleus at the mononuclear stage and were compressed into belts and subsequently disappeared in the anther cavity, whereas tapetum cells were swollen and vacuolated, with a delayed degradation to flowering time. Male sterile anthers had an ROS burst and lower levels of major antioxidants, which may cause abnormal development of microspores and tapetum, leading to male sterility in peach. In addition, the male sterility appears to be cytoplasmic in peach, which could be due to sequence variation in the mitochondrial genome. Our results are helpful for further investigation of the genetic mechanisms underlying male sterility in peach.

Abstract Background Foot-and-mouth disease (FMD), which is caused by foot-and-mouth disease virus (FMDV), is a highly contagious tansboundary disease of cloven-hoofed animals and causes devastating economic damages. Accurate, rapid and simple detection of FMDV is critical to containing an FMD outbreak. Recombinase polymerase amplification (RPA) has been explored for detection of diverse pathogens because of its accuracy, rapidness and simplicity. A visible and equipment-free reverse-transcription recombinase polymerase amplification assay combined with lateral flow strip (LFS RT-RPA) was developed to detect the FMDV using primers and LF probe specific for the 3D gene. Results The FMDV LFS RT-RPA assay was performed successfully in a closed fist using body heat for 15 min, and the products were visible on the LFS inspected by the naked eyes within 2 min. The assay could detect FMDV serotypes O, A and Asia1, and there were no cross-reactions with vesicular stomatitis virus (VSV), encephalomyocarditis virus (EMCV), classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus 2 (PCV2) and pseudorabies virus (PRV). The analytical sensitivity was 1.0 × 102 copies in vitro transcribed FMDV RNA per reaction, which was the same as a real-time RT-PCR. For the 55 samples, FMDV RNA positive rate was 45.5% (25/55) by LFS RT-RPA and 52.7% (29/55) by real-time RT-PCR. For the LFS RT-RPA assay, the positive and negative predicative values were 100% and 80%, respectively. Conclusions The performance of the LFS RT-RPA assay was comparable to real-time RT-PCR, while the LFS RT-RPA assay was much faster and easier to be performed. The developed FMDV LFS RT-RPA assay provides an attractive and promising tool for rapid and reliable detection of FMDV in under-equipped laboratory and at point-of-need facility, which is of great significance in FMD control in low resource settings.

(TaSe_{4})_{2}I, a quasi-one-dimensional (1D) crystal, shows a characteristic temperature-driven metal-insulator phase transition. Above the charge density wave (CDW) temperature T_{c}, (TaSe_{4})_{2}I has been predicted to harbor a Weyl semimetal phase. Below T_{c}, it becomes an axion insulator. Here, we performed angle-resolved photoemission spectroscopy measurements on the (110) surface of (TaSe_{4})_{2}I and observed two sets of Dirac-like energy bands in the first Brillouin zone, which agree well with our first-principles calculations. Moreover, we found that each Dirac band exhibits an energy splitting of hundreds of millielectron volts under certain circumstances. In combination with core level measurements, our theoretical analysis showed that this Dirac band splitting is a result of surface charge polarization due to the loss of surface iodine atoms. Our findings here shed light on the interplay between band topology and CDW order in Peierls compounds and will motivate more studies on topological properties of strongly correlated quasi-1D materials.