An Ascovirus Utilizes Different Types of Host Larval Regulated Cell Death Mechanisms To Produce and Release Vesicles.

Ascoviruses are insect-specific viruses that are thought to utilize the cellular apoptotic processes of host larvae to produce numerous virion-containing vesicles. In this study, we monitored the in vivo infection processes of Heliothis virescens ascovirus 3h (HvAV-3h) to illustrate the regulated cell death (RCD) of host cells. Transmission electron microscopic observations did not reveal any morphological markers of apoptosis in the fat bodies or hemocytes of HvAV-3h-infected Helicoverpa armigera or Spodoptera exigua larvae. However, several hemocytes showed the morphological criteria for necrosis and/or pyroptosis. Further in vitro biochemical tests were performed to confirm the RCD type of host cells after infection with HvAV-3h. Different morphological characteristics were found between the early (prior to 24 hours post-infection, [hpi]) and later (48 to 120 hpi) stages in both HvAV-3h infected larval fat bodies and hemocytes. In the early stages, the virions could only be found in several adipohemocytes, and the fat bodies were cleaving their contained lipid inclusions into small lipid dots. In the later stage, both fat bodies and hemocytes were filled with numerous virions. According to the morphological characteristics of HvAV-3h infected larval fat bodies or hemocytes, the pathogenic characteristics and infection patterns of HvAV-3h in the host larvae were described, and the systematic pathogenic mode of ascovirus infection was refined in this study. This study details the complete infection process of ascoviruses, which provides insights into the relationship between a pathogenesis of an insect virus and the RCD of different host tissues at different stages of infection. IMPORTANCE Viruses and other pathogens can interrupt host cellular apoptosis to gain benefits, such as sufficient resources and a stable environment that enables them to complete their replication and assembly. It is unusual for viruses to code proteins with homology to caspases, which are commonly recognized as apoptosis regulators. Ascoviruses are insect viruses with special cytopathology, and they have been hypothesized to induce apoptosis in their host larvae via coding a caspase-like protein. This enables them to utilize the process of cellular apoptosis to facilitate vesicle formation and replication. However, our previous studies revealed different trends. The fat bodies and hemocytes of Heliothis virescens ascovirus 3h (HvAV-3h)-infected larvae did not show any morphological markers of apoptosis but did display necrosis and/or pyroptosis morphological characteristics. The pathogenic characteristics and infection patterns of HvAV-3h in the host larvae were described, which can help us understand the relationship between the pathogenesis of an insect virus and host RCD.

The impact of diabetes mellitus on cardiac function assessed by magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

Glycemic control and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: insight from ventricular remodeling using cardiac MRI.

BACKGROUND: Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. METHODS: A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c < 6.5% (intensive control), HbA1c 6.5-7.5% (modest control), and HbA1c > 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. RESULTS: Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c < 6.5%: hazard ratio (HR) = 2.42, 95% confidence interval (CI) = 1.07-5.45; P = 0.033; HbA1c > 7.5%: HR = 2.24, 95% CI = 1.01-4.99; P = 0.038] and secondary outcomes (HbA1c < 6.5%: HR = 2.84, 95% CI = 1.16-6.96; P = 0.022; HbA1c > 7.5%: HR = 2.65, 95% CI = 1.08-6.50; P = 0.038) compared with those in the middle HbA1c category. CONCLUSIONS: We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.

Sex differences in clinical profile, left ventricular remodeling and cardiovascular outcomes among diabetic patients with heart failure and reduced ejection fraction: a cardiac-MRI-based study.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. METHODS: A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. RESULTS: Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. CONCLUSIONS: Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study.

BACKGROUND: Microvascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique. METHODS: Twelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function. RESULTS: With the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = - 0.353, P = 0.022), LV remodeling index (r = - 0.312, P = 0.033), fasting blood glucose (r = - 0.313, P = 0.043), and HbA1c (r = - 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration. CONCLUSIONS: Myocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI.

BACKGROUND: Sarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition. METHODS: A total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model. RESULTS: Patients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (ß = -0.25; P < 0.001), rather than body mass index (ß = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4-52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92-0.99; P = 0.01). CONCLUSIONS: With respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

Free-Breathing Compressed Sensing Cine Cardiac MRI for Assessment of Left Ventricular Strain by Feature Tracking in Children.

BACKGROUND: Cardiac MRI feature-tracking (FT) with breath-holding (BH) cine balanced steady state free precession (bSSFP) imaging is well established. It is unclear whether FT-strain measurements can be reliably derived from free-breathing (FB) compressed sensing (CS) bSSFP imaging. PURPOSE: To compare left ventricular (LV) strain analysis and image quality of an FB CS bSSFP cine sequence with that of a conventional BH bSSFP sequence in children. STUDY TYPE: Prospective. SUBJECTS: 40 children able to perform BHs (cohort 1 [12.1 ± 2.2 years]) and 17 children unable to perform BHs (cohort 2 [5.2 ± 1.8 years]). FIELD STRENGTH/SEQUENCE: 3T, bSSFP sequence with and without CS. ASSESSMENT: Acquisition times and image quality were assessed. LV myocardial deformation parameters were compared between BH cine and FB CS cine studies in cohort 1. Strain indices and image quality of FB CS cine studies were also assessed in cohort 2. Intraobserver and interobserver variability of strain parameters was determined. STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient (ICC), and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: In cohort 1, the mean acquisition time of the FB CS cine study was significantly lower than for conventional BH cine study (15.6 s vs. 209.4 s). No significant difference were found in global circumferential strain rate (P = 0.089), global longitudinal strain rate (P = 0.366) and EuroCMR image quality scores (P = 0.128) between BH and FB sequences in cohort 1. The overall image quality score of FB CS cine in cohort 2 was 3.5 ± 0.5 with acquisition time of 14.7 ± 2.1 s. Interobserver and intraobserver variabilities were good to excellent (ICC = 0.810 to 0.943). DATA CONCLUSION: FB CS cine imaging may be a promising alternative technique for strain assessment in pediatric patients with poor BH ability. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Association of Pulmonary Transit Time and Pulmonary Blood Volume From First-Pass Perfusion Cardiac MRI With Diastolic Dysfunction and Left Ventricle Deformation in Restrictive Cardiomyopathy.

BACKGROUND: Patients with restrictive cardiomyopathy (RCM) have impaired diastolic filling and hemodynamic congestion. Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) reflect the hemodynamic status, but the relationship with left ventricle (LV) dysfunction remains unclear. PURPOSE: To evaluate the PTT and PBVi in RCM patients, the association with diastolic dysfunction and LV deformation, and the effects on the occurrence of major adverse cardiac events (MACE) in RCM patients. STUDY TYPE: Retrospective. POPULATION: 137 RCM patients (88 men, age 58.80 ± 10.83 years) and 68 age- and sex-matched controls (46 men, age 57.00 ± 8.59 years). FIELD STRENGTH/SEQUENCE: 3.0T/Balanced steady-state free precession sequence, recovery prepared echo-planar imaging sequence, and phase-sensitive inversion recovery sequence. ASSESSMENT: The LV function and peak strain (PS) parameters were measured. The PTT was calculated and corrected by heart rate (PTTc). The PBVi was calculated as the product of PTTc and RV stroke volume index. STATISTICAL TESTS: Chi-squared test, student's t-test, Mann-Whitney U test, Pearson's or Spearman's correlation, multivariate linear regression, Kaplan-Meier survival analysis, and Cox regression models analysis. A P-value <0.05 was considered statistically significant. RESULTS: The PTTc showed a significant correlation with the E/A ratio (r = 0.282), and PBVi showed a significant correlation with the E/e' ratio, E/A ratio, and diastolic dysfunction stage (r = 0.222, 0.320, and 0.270). PTTc showed an independent association with LVEF, LV circumferential PS, and LV longitudinal PS (ß = 0.472, 0.299, and 0.328). In Kaplan-Meier analysis, higher PTTc and PBVi were significantly associated with MACE. In multivariable Cox regression analysis, PTTc was a significantly independent predictor of the MACE in combination with both cardiac MRI functional and tissue parameters (hazard ratio: 1.23/1.32, 95% confidence interval: 1.10-1.42/1.20-1.46). DATA CONCLUSION: PTTc and PBVi are associated with diastolic dysfunction and deteriorated LV deformation, and PTTc independently predicts MACE in patients with RCM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Infantile hemangioma in a subadult Chinese pangolin: a case report.

BACKGROUND: Hemangiomas are a relatively common type of tumor in humans and animals. Various subtypes of hemangiomas have been described in the literature. The classification methods for hemangiomas differ between human and veterinary medicine, and the basis for tumor classification can be found in the literature. CASE PRESENTATION: This study describes a tumor in the subcutaneous tissue of the right dorsum of an artificially rescued juvenile Chinese pangolin. Computed tomography (CT) examination yielded the preliminary diagnosis of a vascular malformation, and surgery was performed to resect the tumor. Histopathological examination showed that the tumor mainly was consisted of adipose tissue, capillaries, and spindle cells in the fibrous stroma. Immunohistochemistry showed the positive expression of CD31, CD34, α-SMA, GLUT1 and WT-1 in the tumor tissue, and the tumor was eventually diagnosed as an infantile haemangioma. CONCLUSION: The final diagnosis of infantile hemangioma was depended on the histopathological immunohistochemical and CT examination of the neoplastic tissue. This is the first report of infantile hemangioma in a critically endangered species Chinese pangolin.

Left ventricular concentric hypertrophy with cardiac magnetic resonance imaging improves risk stratification in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: The development of left ventricular (LV) remodeling has been associated with an increased cardiovascular risk and cardiogenic death, and different patterns of remodeling result in varying levels of prognosis. OBJECTIVE: To investigate the association between different patterns of LV remodeling and clinical outcomes in the preclinical stage of patients with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: A total of 148 patients with DMD and 43 sex- and age-matched healthy participants were enrolled. We used the four-quadrant analysis method to investigate LV remodeling based on cardiac magnetic resonance (MR) imaging. Kaplan-Meier curves were generated to illustrate the event-free survival probability stratified by the LV remodeling pattern. Cox regression models were constructed and compared to evaluate the incremental predictive value of the LV remodeling pattern. RESULTS: During the median follow-up period of 2.2 years, all-cause death, cardiomyopathy, and ventricular arrhythmia occurred in 5, 35, and 7 patients, respectively. LV concentric hypertrophy (hazard ratio 2.91, 95% confidence interval 1.47-5.75, P=0.002) was an independent predictor of composite endpoint events. Compared to the model without LV concentric hypertrophy, the model with LV concentric hypertrophy had significant incremental predictive value (chi-square value 33.5 vs. 25.2, P=0.004). CONCLUSION: Age and late gadolinium enhancement positivity were positively correlated with clinical outcomes according to the prediction models. LV concentric hypertrophy was also an independent predictor for risk stratification and provided incremental value for predicting clinical outcomes in the preclinical stage of patients with DMD.

Health hazards of preconception phthalate exposure: A scoping review of epidemiology studies.

There is a close relationship between preconception health and maternal and child health outcomes, and the consequences may be passed down from generation to generation. In 2018, Lancet published three consecutive articles emphasizing the importance of the preconception period. Phthalic acid ester (PAE) exposure during this period may affect gametogenesis and epigenetic information in gametophytes, thereby affecting embryonic development and offspring health. Therefore, this article reviews the effects of parental preconception PAE exposure on reproductive/birth outcomes and offspring health, to provide new evidence on this topic. We searched Web of Science, MEDLINE (through PubMed), the China National Knowledge Infrastructure (CNKI), ScienceDirect, and the VIP Journal Library from the date of database establishment to July 3, 2024. Finally, 12 articles were included. Three studies investigated the health hazards (effects on birth weight, abortion, etc.) of women's preconception PAE exposure. Nine studies involved both parents. Nine studies considered the impacts of PAE preconception exposure on reproductive/birth outcomes, focusing on birth weight, pregnancy loss, preterm birth, embryo quality, and placental weight. Three studies considered the impacts of preconception PAE exposure on offspring behavior. The results of this review suggested that parental preconception PAE exposure may have an impact on reproductive/birth outcomes and offspring behavior, including birth weight, child behavior, and dietary behavior. However, studies on the health hazards of preconception PAE exposure are relatively scarce, and the outcomes of current studies are varied. It is necessary to use systematic reviews to verify an accurate research question to provide recommendations for public health policy making.

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In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Constraint-induced movement therapy alleviates motor impairment by inhibiting the accumulation of neutrophil extracellular traps in ischemic cortex.

Stroke is a major cause of mortality and morbidity and most acute strokes are ischemic. Evidence-based medicine has demonstrated the effectiveness of constraint-induced movement therapy (CIMT) in the recovery of motor function in patients after ischemic stroke, but the specific treatment mechanism remains unclear. Herein, our integrated transcriptomics and multiple enrichment analysis studies, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) studies show that CIMT conduction broadly curtails immune response, neutrophil chemotaxis, and chemokine-mediated signaling pathway, CCR chemokine receptor binding. Those suggest the potential effect of CIMT on neutrophils in ischemic mice brain parenchyma. Recent studies have found that accumulating granulocytes release extracellular web-like structures composed of DNA and proteins called neutrophil extracellular traps (NETs), which destruct neurological function primarily by disrupting the blood-brain barrier and promoting thrombosis. However, the temporal and spatial distribution of neutrophils and their released NETs in parenchyma and their damaging effects on nerve cells remain unclear. Thus, utilizing immunofluorescence and flow cytometry, our analyses uncovered that NETs erode multiple regions such as primary motor cortex (M1), striatum (Str), nucleus of the vertical limb of the diagonal band (VDB), nucleus of the horizontal limb of the diagonal band (HDB) and medial septal nucleus (MS), and persist in the brain parenchyma for at least 14 days, while CIMT can reduce the content of NETs and chemokines CCL2 and CCL5 in M1. Intriguingly, CIMT failed to further reduce neurological deficits after inhibiting the NET formation by pharmacologic inhibition of peptidylarginine deiminase 4 (PAD4). Collectively, these results demonstrate that CIMT could alleviate cerebral ischemic injury induced locomotor deficits by modulating the activation of neutrophils. These data are expected to provide direct evidence for the expression of NETs in ischemic brain parenchyma and novel insights into the mechanisms of CIMT protecting against ischemic brain injury.

Correction: Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?

[This corrects the article DOI: 10.1371/journal.ppat.1008421.].

Fisheye lens-based UWOC system with an FOV of ±90°.

The link alignment is a challenge in underwater wireless optical communication (UWOC). This paper proposes a UWOC system adopting a fisheye lens with a field of view (FOV) of ±90° at the receiver to alleviate alignment requirement, and a mobile scanning device (MSD) is exploited to track the variation of the imaging position generated by the fisheye lens due to different incidence angles. In a 7-m tap water channel, a transmission with a data rate of 400 Mbps and an FOV of ±90° is realized with 16-quadrature amplitude modulating-orthogonal frequency division multiplexing (16-QAM-OFDM) modulation and orthogonal matching pursuit (OMP) channel estimation algorithm.

Association of diabetes mellitus and glycemic control with left ventricular function and deformation in patients after acute myocardial infarction: a 3 T cardiac magnetic resonance study.

BACKGROUND: Diabetes mellitus (DM) is considered a major risk factor for myocardial infarction (MI), and MI patients with DM have a poor prognosis. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients after acute MI. MATERIALS AND METHODS: One hundred thirteen MI patients without DM [MI (DM-)], 95 with DM [MI (DM+)] and 71 control subjects who underwent CMRscanning were included. LV function, infarct size and LV global peak strains in the radial, circumferential and longitudinal directions were measured. MI (DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV global myocardial strain for all MI patients and MI (DM+) patients were assessed using multivariable linear regression analyses. RESULTS: Compared with control subjects, both MI (DM-) and MI (DM+) patients presented higher LV end-diastolic and end-systolic volume index and lower LV ejection fraction. LV global peak strains progressively declined from the control group to the MI(DM-) group to the MI(DM+) group (all p < 0.05). Subgroup analysis showed that LV global radial PS and longitudinal PS were worse in MI(MD+) patients with poor glycemic control than in those with good glycemic control (all p < 0.05). DM was an independent determinant of impaired LV global peak strain in radial, circumferential and longitudinal directions in patients after acute MI (ß = - 0.166, 0.164 and 0.262, both p < 0.05). The HbA1c level was independently associated with a decreased LV global radial PS (ß = - 0.209, p = 0.025) and longitudinal PS (ß = 0.221, p = 0.010) in MI (DM+) patients. CONCLUSIONS: DM has an additive deleterious effect on LV function and deformation in patients after acute MI, and HbA1c was independently associated with impaired LV myocardial strain.

Early longitudinal changes in left ventricular function and morphology in diabetic pigs: evaluation by 3.0T magnetic resonance imaging.

BACKGROUND: Previous researches on large animal models of diabetic cardiomyopathy were insufficient. The aim of this study was to evaluate early changes in left ventricular (LV) function and morphology in diabetic pigs using a cardiac magnetic resonance (CMR) time-volume curve and feature tracking technique. METHODS: Streptozotocin (STZ) was used to induce diabetic in sixteen pigs. 3.0T MRI scanned the pig's heart before and 2, 6, 10 and 16 months after modelling. CMR biomarkers, including time-volume curve and myocardial strain, were compared to analyse the longitudinal changes in LV function and morphology. Pearson correlation was used to evaluate the relationship between LV strain and remodelling. Cardiac specimens were obtained at 6, 10, and 16 months after modelling to observe the myocardial ultrastructural and microstructure at different courses of diabetes. RESULTS: Twelve pigs developed diabetes. The 80% diastolic volume recovery rate (DVR) at 6 months after modelling was significantly higher than that before modelling (0.78 ± 0.08vs. 0.67 ± 0.15). The LV global longitudinal peak strain (GLPS) (- 10.21 ± 3.15 vs. - 9.74 ± 2.78 vs. - 9.38 ± 3.71 vs. - 8.71 ± 2.68 vs. - 6.59 ± 2.90%) altered gradually from the baseline data to 2, 6, 10 and 16 months after modelling. After 16 months of modelling, the LV remodelling index (LVRI) of pigs increased compared with that before modelling (2.19 ± 0.97 vs. 1.36 ± 0.45 g/ml). The LVRI and myocardial peak strain were correlated in diabetic pigs (r= - 0.40 to - 0.54), with GLPS being the most significant. Electron microscopy and Masson staining showed that myocardial damage and fibrosis gradually increased with the progression of the disease. CONCLUSION: Intravenous injection of STZ can induce a porcine diabetic cardiomyopathy model, mainly characterized by decreased LV diastolic function and strain changes accompanied by myocardial remodelling. The changes in CMR biomarkers could reflect the early myocardial injury of diabetic cardiomyopathy.

Effects of diabetes mellitus on left ventricular function and deformation in patients with restrictive cardiomyopathies: a 3.0T CMR feature tracking study.

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disease worldwide and a major risk factor for adverse cardiovascular events, while the additive effects of DM on left ventricular (LV) deformation in the restrictive cardiomyopathy (RCM) cohort remain unclear. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients with RCM. MATERIALS AND METHODS: One hundred thirty-six RCM patients without DM [RCM(DM-)], 46 with DM [RCM (DM+)], and 66 age- and sex-matched control subjects who underwent cardiac magnetic resonance (CMR) scanning were included. LV function, late gadolinium enhancement (LGE) type, and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured. The determinant of reduced LV global myocardial strain for all RCM patients was assessed using multivariable linear regression analyses. The receiver operating characteristic curve (ROC) was performed to illustrate the relationship between DM and decreased LV deformation. RESULTS: Compared with the control group, RCM (DM-) and RCM(DM+) patients presented increased LV end-diastolic index and end-systolic volume index and decreased LV ejection fraction. LV GPS in all three directions and longitudinal PDSR progressively declined from the control group to the RCM(DM-) group to the RCM(DM+) group (all p < 0.05). DM was an independent determinant of impaired LV GPS in the radial, circumferential, and longitudinal directions and longitudinal PDSR (ß = - 0.217, 0.176, 0.253, and - 0.263, all p < 0.05) in RCM patients. The multiparameter combination, including DM, showed an AUC of 0.81(95% CI 0.75-0.87) to predict decreased LV GLPS and an AUC of 0.69 (95% CI 0.62-0.76) to predict decreased LV longitudinal PDSR. CONCLUSIONS: DM may have an additive deleterious effect on LV dysfunction in patients with RCM, especially diastolic dysfunction in RCM patients, indicating the importance of early identification and initiation of treatment of DM in patients with RCM.

The right ventricular dysfunction and ventricular interdependence in patients with DM: assessment using cardiac MR feature tracking.

BACKGROUND: To investigate the difference of right ventricular (RV) structural and functional alteration in patients with diabetes mellitus (DM) with preserved left ventricular ejection fraction (LVEF), and the ventricular interdependence in these patients, using cardiac MR (CMR) feature tracking. METHODS: From December 2016 to February 2022, 148 clinically diagnosed patients with DM who underwent cardiac MR (CMR) in our hospital were consecutively recruited. Fifty-four healthy individuals were included as normal controls. Biventricular strains, including left/right ventricular global longitudinal strain (LV-/RVGLS), left/right ventricular global circumferential strain (LV-/RVGCS), left/right ventricular global radial strain (LV-/RVGRS) were evaluated, and compared between patients with DM and healthy controls. Multiple linear regression and mediation analyses were used to evaluate DM's direct and indirect effects on RV strains. RESULTS: No differences were found in age (56.98 ± 10.98 vs. 57.37 ± 8.41, p = 0.985), sex (53.4% vs. 48.1%, p = 0.715), and body surface area (BSA) (1.70 ± 0.21 vs. 1.69 ± 0.17, p = 0.472) between DM and normal controls. Patients with DM had decreased RVGLS (- 21.86 ± 4.14 vs. - 24.49 ± 4.47, p = 0.001), RVGCS (- 13.16 ± 3.86 vs. - 14.92 ± 3.08, p = 0.011), and no decrease was found in RVGRS (22.62 ± 8.11 vs. 23.15 ± 9.05, p = 0.743) in patients with DM compared with normal controls. The difference in RVGLS between normal controls and patients with DM was totally mediated by LVGLS (indirect effecting: 0.655, bootstrapped 95%CI 0.138-0.265). The difference in RVGCS between normal controls and DM was partly mediated by the LVGLS (indirect effecting: 0.336, bootstrapped 95%CI 0.002-0.820) and LVGCS (indirect effecting: 0.368, bootstrapped 95%CI 0.028-0.855). CONCLUSIONS: In the patients with DM and preserved LVEF, the difference in RVGLS between DM and normal controls was totally mediated by LVGLS. Although there were partly mediating effects of LVGLS and LVGCS, the decrease in RVGCS might be directly affected by the DM.