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Abstract Background Fibrosing mediastinitis (FM) is a rare yet fatal condition, caused by different triggers and frequently culminating in the obstruction of the pulmonary vasculature and airways, often leading to pulmonary hypertension and right heart failure. Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by FM. Our previous study showed as high as 24% of in-stent restenosis (ISR) in FM. However, the predictors of ISR are elusive. Objectives We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM. Methods We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR. Results A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4–15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98; P = 0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86; P = 0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-up, respectively. Conclusion ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis. Trail Registration Chinese Clinical Trials Register; No.: ChiCTR2000033153. URL: http://www.chictr.org.cn . Graphical Abstract

Abstract Introduction Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. Case presentation An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent. Conclusions This report may provide new management ideas for the interventional treatment of PV occlusion.

Abstract Background Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non‐invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD–PH). Methods This study included 535 patients with COPD–PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD–PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan–Meier curves were used for a survival analysis. The nomograms were developed as online network software. Results Tricuspid regurgitation velocity, right ventricular diameter, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), the red blood cell count, New York Heart Association functional class and sex were non‐invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT‐proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD–PH and were used to create a predictive nomogram of overall survival rates. Conclusions The proposed nomograms based on a large sample size of patients with COPD–PH could be used as non‐invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD–PH. Additionally, the online network has the potential to provide artificial intelligence‐assisted diagnosis and treatment. Highlights A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non‐invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD–PH.

Chronic pulmonary artery stenosis (CPAS) is characterized by a reduction or complete obstruction of the cross-sectional area of the pulmonary artery owing to various causes. The condition exhibits similar pathophysiological progress, leading to pulmonary hypertension (PH), reduced physical endurance, right heart failure, and death. Although CPAS is often regarded as a subgroup of PH, it can manifest independently for an extended duration before the onset of PH and can significantly impact patient quality of life. It may therefore be more appropriate to consider PH as pathophysiological progression of CPAS, thereby recognizing CPAS as a distinct disease entity.

Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P

Abstract The Wilson fermion (WF) is a fundamental particle in the theory of quantum chromodynamics. Theoretical calculations have shown that the WF with a half skyrmion profile represents a quantum anomalous semimetal phase supporting a chiral edge current, but the experimental evidence is still lacking. In this work, we report a direct observation of the WF in circuit systems. We find that WFs manifest as topological spin textures analogous to the half skyrmion, half-skyrmion pair, and Néel skyrmion structures, depending on their mass. Transformations of different WF states are realized by tuning the electric elements. We further experimentally observe the propagation of chiral edge current along the domain-wall separating two circuits with contrast fractional Chern numbers. Our work provides experimental evidence for WFs in topolectrical circuits. The nontrivial analogy between the WF state and the skyrmionic structure builds an intimate connection between the two burgeoning fields.

Abstract Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets.

Pulmonary vein stenosis (PVS) is an extremely rare and lethal disease caused by multiple etiologies. PVS has a bimodal distribution in the population, affecting children and adults. Congenital PVS is the usual PVS type in children, which sometimes develops after cardiothoracic surgery. Acquired PVS, in turn, is the most common PVS type in adults. A review of the relevant literature has shown that PVS after radiofrequency ablation of atrial fibrillation is the most common, as well as that caused by compression of proliferative fibrous tissues or tumor in the mediastinum (eg, PVS caused by fibrosing mediastinitis, lung tumors, metastases, etc). This article provides a comprehensive review of PVS in terms of embryology and anatomy, etiology and triggers, classification, clinical symptoms and signs, treatment, and prognosis, intending to promote the understanding and treatment of this disease.

Abstract Fibrosing mediastinitis (FM) is a rare disease caused by different causes. If left untreated, the prognosis is poor. The common causes of FM are Tuberculosis and Histoplasma capsulatum infection. Esophageal perforation is also a rare condition that is often easily under‐ and mis‐diagnosed due to the lack of specificity of symptoms. Here we report a case of FM caused by esophageal perforation.

Abstract Background G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. Methods In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. Results A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P T and c.946G>A) were identified. Conclusions This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.

The topological properties of square-root Weyl semimetals are derived from the square of the Hamiltonian. Here, the authors propose a tight-binding model for a square-root higher-order Weyl semimetal hosting both Fermi-arc surface and hinge states.

Background: Misdiagnosis and underdiagnosis of pulmonary hypertension caused by fibrosing mediastinitis (PH-FM) are considerably prevalent due to unspecific symptoms and as well as the lack of awareness of this fatal disease. Objectives: The aim of this study was to evaluate the diagnostic accuracy of the chest X-ray (CXR) for screening the patients with PH-FM from those with pulmonary hypertension (PH). Design: This was a retrospective observational cohort study. Methods: The patients with suspected PH were recruited between October 2014 and October 2020. All the clinical data and CXR findings were collected. The sensitivity, specificity, and likelihood ratio of the CXR features were calculated. Logistic regression was used to identify the factors associated with the CXR characteristics and FM and to generate a prediction model. Finally, the diagnostic efficiency of the prediction model was evaluated using nomogram and internal validation. Results: The patients with PH-FM ( n = 36) and PH caused by the diseases other than FM (PH-non-FM, n = 62) were enrolled. The CXR features, including atelectasis, pleural effusion, consolidation, nodules, calcification, interlobular septal thickening, and interstitial reticulation, were more prevalent in patients with PH-FM than in those with PH-non-FM (all p

Acute coronary syndrome (ACS) is a severe type of coronary heart disease (CHD) with increasing prevalence and significant challenges for prevention and treatment. Metabolomics is an emerging technology with intrinsic dynamics and flexibility to better delineate the phenotypic and metabolic alterations in organisms at the time of altered pathological states. It provides new insights into the complex pathological mechanisms of cardiovascular disease and contributes to the early detection, monitoring and evaluation of ACS. In this review, we analyze and summarize the literature related to ACS metabolomics which has contributed to the diagnosis and prevention of ACS.

Purpose: To detect previously undetectable changes in vessel density and structural thickness, the two biomechanics-related parameters reflecting hemodynamics and tensile strength, respectively, in the peripheral and central fundi of nonpathological myopic eyes with an advanced ultrawide-field optical coherence tomography angiography (OCTA) system.Methods: A cross-sectional observational clinical study was carried out by recruiting 155 eyes from 79 college students aged 18–28 years. The eyes were stratified into normal, low-myopia, medium-myopia, and high-myopia groups according to diopter. A newly developed OCTA system with scanning dimensions of 24 mm × 20 mm, acquisition speed of 400 kHz, and imaging range of 6 mm was used to examine the vessel densities of superficial vascular complex (SVC), deep vascular complex (DVC), choriocapillary (ChC), and choroidal vessel (ChV) layers, as well as the thicknesses of the inner retina, outer retina, and choroid in the nonpathological myopic eyes.Results: The vessel densities in ChV at the temporal, inferotemporal, inferior, and inferonasal regions in the fundus periphery were significantly reduced in myopic subjects as compared to normal controls (all p < 0.05). The thicknesses of the inner retinal segments in most peripheral regions of the fundus became attenuated along with myopia severity (all p < 0.05). The thicknesses of the outer retinal segments were diminished at the superior and supranasal regions of the peripheral fundi of myopic subjects as compared to normal controls (all p < 0.05). At the central macular region, the decreased vessel densities of SVC and DVC were correlated with the attenuated thicknesses of inner retinal segments, respectively (all p < 0.05).Conclusion: As revealed for the first time by the advanced ultrawide-field OCTA system, the two biomechanics-related parameters that include the densities of the choroidal vessels and thicknesses of the inner retina segments were significantly reduced in the periphery of nonpathological myopic fundi and the reductions were associated with myopia severity. At the central macular region, the newly developed device provides consistent results with the previous findings. Therefore, it is important to use the noninvasive, ultrawide-field OCTA with high resolution for early detection of fundus changes in subjects with nonpathological high myopia.Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2100054093.

Abstract Lymphomatoid granulomatosis is a rare, vascular‐centric, and vessel‐destroying lymphoproliferative disease that hardly involves the pulmonary arteries. Herein, we report a case with severe right heart failure and pulmonary arterial stenosis caused by pulmonary artery lymphomatoid granulomatosis. This case was diagnosed by percutaneous transluminal pulmonary artery biopsy and was effectively treated with stent implantation and steroid administration.

Abstract Coronavirus disease 2019 (COVID‐19) causes a pandemic around the globe. Debilitating and even deadly complications have occurred to the millions. A recent study reported 31% of right ventricular dilation in the hospitalized COVID‐19 patients, which is significantly associated with the mortality. Therefore, we sought to search for the lines of evidence in the literature that COVID‐19 may contribute to right heart dysfunction. The relevant literature and data from PubMed, Embase, Cochrane Library databases, and Web of Science were searched using the MeSH terms including ‘COVID‐19’, ‘SARS‐CoV‐2’, ‘novel coronavirus pneumonia’, ‘novel coronavirus’, ‘right heart failure’, ‘right heart dysfunction’, ‘pulmonary hypertension’, ‘pulmonary embolism’, and various combinations. The collected literature and data were sorted and summarized. Literature reports that angiotensin‐converting enzyme 2 (ACE2) is the host receptor mediating the cell entry of severe acute respiratory syndrome coronavirus 2. Clinical and experimental evidence shows that loss of function of ACE2 aggravates pulmonary hypertension and gain of function of ACE2 exerts protection on cardiopulmonary circulation. Moreover, the patients with COVID‐19 are more susceptible to pulmonary embolism and severe pneumonia‐induced acute respiratory distress syndrome. Therefore, COVID‐19 may cause right heart dysfunction by inducing pulmonary hypertension, pulmonary embolism, and acute respiratory distress syndrome. Particular attention should be paid to the function of the right heart, the overlooked chamber in COVID‐19. Blood gas analysis, laboratory test of cardiac injury markers, physical examination, and echocardiography should be performed to identify right heart failure as early as possible. Once the right heart failure is confirmed, the therapeutic modalities following the guidelines of European Society of Cardiology should be employed to reduce mortality.

Abstract Background Whether glutathione S-transferase (GST) null polymorphisms, namely GSTM1 null, GSTP1 null and GSTT1 null polymorphisms, influence the risk of coronary artery disease (CAD) or not remains unclear. Thus, the authors performed a meta-analysis to more robustly estimate associations between GST null polymorphisms and the risk of CAD by integrating the results of previous publications. Methods Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible studies, and 45 genetic association studies were finally selected to be included in this meta-analysis. Results We found that GSTM1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.37, p = 0.003) and mixed population (OR = 1.61, p = 0.004), GSTP1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.03), whereas GSTT1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.02), Caucasians (OR = 1.23, p = 0.02) and East Asians (OR = 1.38, p

We propose a method to generate magnetic skyrmions by focusing spin waves totally reflected by a curved film edge. The edge contour is derived to be parabolic and frequency-independent based on the identical magnonic path length principle. We performed micromagnetic simulations to verify our theoretical design. Under proper conditions, the reflected spin waves first converge at the focal point with the enhanced intensity leading to the emergence of magnetic droplets, which are then converted to magnetic skyrmion accompanied by a change in the topological charge. We numerically obtain the phase diagram of skyrmion generation with respect to the amplitude and frequency of the driving field. Our finding would be helpful for the design of spintronic devices combining the advantage of skyrmionics and magnonics.

As a common disease, hypertension (HTN) can lead to severe complications such as heart failure, renal failure and stroke. However, delayed diagnosis often happens because of no obvious symptoms in earlier stage. This paper addresses the issue through a novel cloud based auxiliary medical system for HTN. Nowadays, telemedicine has been used to diagnose and monitor HTN by sharing and consulting personal health status with doctors. Its high flexibility and processing ability have helped to reduce the overall cost of medical care and enhanced the control rate. Technically, telemedicine uses communication, holographic imaging and computer science to achieve the management for long-distance patients. This paper presents a novel system based on cloud computing and mobile Internet, which can provide telemedicine services for HTN patients. This system could help patients reduce costs, provide flexible communication platform and powerful computing services, and also automatically collect patients’ blood pressure status. As an auxiliary medical system, the data of patients can be processed with instant status feedbacks in the cloud environment, thus patients can actually know their current cardiac status and take necessary measures for efficient management. Also, related doctors could help patients resolve mild symptoms out of office. Keywords: Hypertension, Telemedicine, Cloud computing, Mobile internet

Abstract Background Familial hypercholesterolemia (FH) can lead to premature coronary heart disease. Anticardiolipin antibody may be a contributor for thrombosis. Here, we report an adult with possible FH suffered from premature myocardial infarction that may be triggered by transient increased anticardiolipin antibody. Case presentation A 29-year-old male had presented with a history of 2-h chest pain and numbness of left upper arm before 5 days. The electrocardiogram (ECG) had demonstrated inferior wall myocardial infarction (MI). Five days later he was admitted to our hospital and diagnosed as acute MI and possible FH (premature coronary heart disease, low density lipoprotein cholesterol of 5.90 mmol/L) with increased anticardiolipin antibody (up to 120 RU/ml). Other auto-antibodies including β2-glicoprotein antibodies IgM, IgA, IgG, lupus anticoagulant (LA), antinuclear antibodies, anti-myocardial antibody were normal. Coronary artery angiography (CAG) showed right coronary artery was total occlusion from the middle segment. Then he underwent percutaneous coronary intervention with a stent. Four days later, he was discharged with complete recovery. CAG showed intra-stent restenosis and anticardiolipin antibody level was normal and the patient had no any symptoms at 6-month follow-up. Conclusions Transient elevated anticardiolipin antibody may be a trigger or biomarker of cardiac thrombotic events in younger atherosclerotic patients.

Pulmonary endarterectomy (PEA) is used to treat chronic thromboembolic pulmonary hypertension (CTEPH) patients, and it can effectively remove organized thrombotic materials and proliferative intima as well as improve hemodynamics. It has been reported that the levels of several inflammatory factors were altered in the peri-operative period of PEA. Even though their specific role remains unknown, this could have some relevance. In this study, we reviewed the recently published data addressing these factors in PEA, attempting to understand their potential implications.

Electromagnetic metasurfaces with excellent electromagnetic wave regulation properties are promising for designing high-performance polarization control devices, while the application prospect of electromagnetic metasurfaces is limited because of the current development situations of the complex structure, low conversion efficiency, and narrow working bandwidth. In this work, we design a type of reflective terahertz metasurface made of a simple structure that can achieve multiple polarization modulation with high efficiency. It is shown that the presented metasurface can realize ultra-broadband, cross-polarization conversion with the relative working bandwidth reaching 94% and a conversion efficiency of over 90%. In addition, the proposed metasurface can also efficiently accomplish different polarization conversion functions, such as linear-to-linear, linear-to-circular, or circular-to-linear polarization conversion in multiple frequency bands. Due to the excellent properties, the designed metasurface can be used as a high-efficiency multi-functional polarization modulation device, and it has important application value in terahertz imaging, communication, biological detection, and other fields.

Pulmonary thromboembolism (PTE) is the third leading cause of death in cardiovascular diseases. PTE is believed to be caused by thrombi detached from deep veins of lower extremities. The thrombi travel with systemic circulation to the lung and block pulmonary arteries, leading to sudden disruption of hemodynamics and blood gas exchange. However, this concept has recently been challenged by accumulating evidence demonstrating that de novo thrombosis may be formed in pulmonary arteries without deep venous thrombosis. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH), a subtype of pulmonary hypertension, could have different pathogenesis than traditional PTE. Therefore, this article summarized and compared the risk factors, the common and specific pathogenic mechanisms underlying PTE, in situ pulmonary artery thrombosis, and CTEPH at molecular and cellular levels, and suggested the therapeutic strategies to these diseases, aiming to facilitate understanding of pathogenesis, differential diagnosis, and precision therapeutics of the three pulmonary artery thrombotic diseases.

Objective Whether splenectomy increases the risk of chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We conducted a systematic review and meta-analysis to explore the association between splenectomy and CTEPH.Design Systematic review and meta-analysis.Data sources PubMed, Embase and Cochrane Library databases.Methods Two authors independently searched and extracted the data. The Newcastle-Ottawa Scale and the Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to assess the quality of the included studies, and each quality item was graded as low risk or high risk. A random-effects model was used to calculate different effective values.Results In total, 8 trials involving 6183 participants fulfilled the inclusion criteria. The overall pooled crude prevalence of splenectomy was 4.0% (95% CI 0.03 to 0.06, I2=71.5%, p

Background: Right ventricular function (RVF) is an independent predictor of prognosis for patients undergoing aortic valve replacement: transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). The effect of transfemoral aortic valve replacement (TF-TAVR) on RVF is uncertain. We aimed to perform a meta-analysis of the effect of TF-TAVR on RVF in patients with aortic stenosis (AS) and compare the effect of TF-TAVR with SAVR. Methods: We searched relevant studies from PubMed, Embase, Cochrane Library databases, and Web of Science. Furthermore, two reviewers (Wang AQ and Cao YS) extracted all relevant data, which were then double checked by another two reviewers (Zhang M and Qi GM). We used the forest plot to present results. Tricuspid annular plane systolic excursion (TAPSE) was the primary outcome. Results: This meta-analysis included 11 studies. There were 353 patients who underwent TF-TAVR, and 358 patients who were subjected to SAVR. There was no significant difference in TAPSE at 1 week and 6 months as well as right ventricular ejection fraction (RVEF) at

Background/Aims: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH’s anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Methods: Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH’s anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH’s protection. Results: Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested partial rescue of functional defects by α-MSH in diabetic retinas; and H&E staining revealed significantly increased thickness of all layers in α-MSH-treated diabetic retinas. Mechanistically, α-MSH corrected aberrant transcript and protein expression of pro-inflammatory factor and tight junction genes in the diseased retinas; moreover, it prevented abnormal changes in TEER and permeability in HG-stimulated RF6A cells, and this anti-hyperpermeability was abolished by a universal MCR blocker or an antagonist specific to MC4R. Conclusions: This study showed previously undescribed protective effects of α-MSH on inhibiting BRB breakdown and vascular leakage, improving electrophysiological functions and morphology in early diabetic retinas, which may be due to its down-regulating pro-inflammatory factors and augmenting tight junctions. α-MSH acts predominantly on MC4R to antagonize hyperpermeability in retinal microvessel endothelial cells.

Background: Acute right heart failure (RHF) is the main cause of death in patients with acute pulmonary embolism and emergent pulmonary hypertension. However, the molecular mechanisms underpinning the acute RHF and the interactions between the right (RV) and left ventricles (LVs) under the diseased condition remain unknown. Methods and results: The Sprague Dawley male rats were randomly divided into the normal control, sham, and pulmonary artery banding (PAB) groups. One hour after the PAB operation, after measuring the haemodynamic and anatomical parameters, the free walls of RV and LV were harvested to detect the differential gene expression profiling by high-throughput RNA sequencing. The results showed that the PAB lead to 50–60% obstruction of the main pulmonary artery, which was accompanied by the significant elevation in the positive rate of rise in RV pressure and the maximum RV pressure as compared to the sham group. Moreover, compared with the counterparts in the sham group, the RV and LV in the PAB group exhibited 2057 differentially expressed genes (DEGs, 1159 upregulated and 898 downregulated) and 1196 DEGs (709 upregulated and 487 downregulated), respectively (DEG criteria: |log 2 fold change| ≥1, q value ≤0.05). In comparison to the sham group, the enriched pathways in the PAB group include nuclear factor-κB signalling pathway, extracellular matrix–receptor interaction, and nucleotide oligomerization domain-like receptor signalling pathway. Conclusions: The PAB rat model exhibited the haemodynamic and gene expression changes in the RV that lead to acute RHF. Further, the acute RHF induced by pressure overload also caused gene expression changes in the LV, suggesting the molecular interactions between the RV and LV under the diseased condition.

Higher-order topological insulators are a new class of topological phases of matter, originally conceived for electrons in solids. It has been suggested that the Z_{N} Berry phase (Berry phase quantized into 2π/N) is a useful tool to characterize the symmetry-protected topological states, whereas the experimental evidence is still elusive. Recently, topolectrical circuits have emerged as a simple yet very powerful platform for studying topological physics that are challenging to realize in condensed-matter systems. Here, we present an experimental observation of second-order corner states characterized by the Z_{3} Berry phase in topolectrical circuits. We demonstrate theoretically and experimentally that the localized second-order topological states are protected by a generalized chiral symmetry of tripartite lattices, and they are pinned to “zero energy.” By introducing extra capacitors within sublattices in the circuit, we are able to examine the robustness of the zero modes against both chiral-symmetry-conserving and breaking disturbances. Our Rapid Communication paves the way for testing exotic topological band theory by electrical-circuit experiments.

Background/Aims: Previous studies have indicated that long non-coding RNAs (lncRNA) are related to the occurrence and development of many human diseases, such as cancer and the HELLP and the brachydactyly syndromes. However, studies of LncRNA in heart failure have not yet been reported. Here, we investigated cardiac lncRNA expression profiles in the myocardial-specific knockout pdk1 gene (KO) mouse model of heart failure. Methods: Cardiac samples were obtained from PDK1 KO and WT mice on postnatal (P) day 8 (P8) and day 40 (P40), and lncRNA expression profiles were analyzed by sequencing and screening using the Arraystar mouse lncRNA microarray. Quantitative real-time PCR analysis of these lncRNAs confirmed the identity of some genes. Results: Comparisons of the KO and control groups showed fold changes of >1.5 in the expression levels of 2,024 lncRNAs at P8, while fold changes of >2 in the expression levels of 4,095 lncRNAs were detected at P40. Nineteen lncRNAs were validated by RT-PCR. Bioinformatic and pathway analyses indicated that mkk7, a sense overlap lncRNA, may be involved in the pathological processes of heart failure through the MAPK signaling pathway. Conclusion: These data reveal differentially expressed lncRNA in mice with a myocardial-specific deletion of the pdk1 gene, which may provide new insights into the mechanism of heart failure in PDK1 knockout mice.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20–20.04 U/g Hb in male and 12.29–23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%–45% of the NMM, female: 30%–79% of the NMM), and low hemolysis-risk CDLs (male: ≥45% of the NMM, female: ≥79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes. [ABSTRACT FROM AUTHOR]