Baricitinib protects ICIs-related myocarditis by targeting JAK1/STAT3 to regulate Macrophage polarization.

PURPOSE: The emergence of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but these drugs can also cause severe immune-related adverse effects (irAEs), including myocarditis. Researchers have become interested in exploring ways to mitigate this side effect, and one promising avenue is the use of baricitinib, a Janus kinase inhibitor known to have anti-inflammatory properties. This study aimed to examine the potential mechanism by which baricitinib in ICIs-related myocarditis. METHODS: To establish an ICIs-related myocarditis model, BALB/c mice were administered murine cardiac troponin I (cTnI) peptide and anti-mouse programmed death 1 (PD-1) antibodies. Subsequently, baricitinib was administered to the mice via intragastric administration. Echocardiography, HE staining, and Masson staining were performed to evaluate myocardial functions, inflammation, and fibrosis. Immunofluorescence was used to detect macrophages in the cardiac tissue of the mice.In vitro experiments utilized raw264.7 cells to induce macrophage polarization using anti-PD-1 antibodies. Different concentrations of baricitinib were applied to assess cell viability, and the release of pro-inflammatory cytokines was measured. The activation of the JAK1/STAT3 signaling pathway was evaluated through western blot analysis. RESULTS: Baricitinib demonstrated its ability to improve cardiac function and reduce cardiac inflammation, as well as fibrosis induced by ICIs. Mechanistically, baricitinib treatment promoted the polarization of macrophages towards the M2 phenotype. In vitro and in vivo experiments showed that anti-PD-1 promoted the release of inflammatory factors. However, treatment with baricitinib significantly inhibited the phosphorylation of JAK1 and STAT3. Additionally, the use of RO8191 reversed the effects of baricitinib, further confirming our findings. CONCLUSION: Baricitinib demonstrated its potential as a protective agent against ICIs-related myocarditis by modulating macrophage polarization. These findings provide a solid theoretical foundation for the development of future treatments for ICIs-related myocarditis.

Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Release and sedimentation behaviors of biochar colloids in soil solutions.

The release of biochar colloids considerably affects the stability of biochar in environment. Currently, information on the release behavior and suspension stability of biochar colloids in real soil solutions is scarce. In this study, 20 soils were collected from different districts in China and the release behavior of biochar colloids and their suspension stability in soil solutions were systematically examined. The results showed that both pyrolysis temperature and biomass source had important effects on the formation of biochar colloids in soil solutions. The formation amount of biochar colloids from low pyrolysis temperatures (400 °C) (average amount of 9.33-16.41 mg/g) were significantly higher than those from high pyrolysis temperatures (700 °C) (average amount of less than 2 mg/g). The formation amount of wheat straw-derived biochar colloids were higher than those of rice straw-derived biochar colloids probably due to the higher O/C ratio in wheat-straw biochar. Further, biochar colloidal formation amount was negatively correlated with comprehensive effect of dissolved organic carbon, Fe and Al in soil solutions. The sedimentation curve of biochar colloids in soil solutions is well described by an exponential model and demonstrated high suspension stability. Around 40% of the biochar colloids were maintained in the suspension at the final sedimentation equilibrium. The settling efficiency of biochar colloids was positively correlated with comprehensive effect of the ionic strength and K, Ca, Na, and Mg contents in soil solutions. Our findings help promote a deeper understanding of biochar loss and stability in the soil-water environment.

Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors.

Early anthracycline-induced cardiotoxicity monitored by echocardiographic Doppler parameters combined with serum hs-cTnT.

PURPOSE: As growing numbers of long-term cancer survivors faced with the cardiac side effects by anthracycline treatment, it is necessary to explore the optimal monitoring method for the early detection of cardiac toxicity. METHODS: We conducted a retrospective analysis of 82 consecutive patients with diffuse large B-cell lymphoma treated with chemotherapy. Echocardiographic Doppler imaging-derived Tei index and mitral annular peak systolic velocity (Sm) measured by tissue Doppler imaging TDI, serum high-sensitivity cardiac troponin T (hs-cTnT) levels, and left ventricular ejection fraction (LVEF) by multigated radionuclide angiography (MUGA) were obtained before, after 2-4, and after 6-8 chemotherapy cycles. Cardiotoxicity was defined as a relative reduction of LVEF ≥10% from the baseline or LVEF <50% as measured by MUGA. RESULTS: Following chemotherapy, 24 (29.3%) patients developed detectable cardiac abnormality during the treatment. Five (6.1%) patients' cardiac function changed from normal baseline LVEF to <50% after the chemotherapy. Echocardiographic pulse wave Doppler Tei index (PW Tei index) (baseline 0.347 ± 0.115 vs 2-4 cycles 0.459 ± 0.161 vs 6-8 cycles 0.424 ± 0.139, P = .000) inversely correlated with systolic (P < .001) and diastolic dysfunction (P < .001). Serum hs-cTnT levels increased significantly following chemotherapy after 2-4 cycles of chemotherapy with anthracycline. The increase in PW Tei index of 0.095 [sensitivity, 69.2%; specificity, 64.5%; area under the curve (AUC) = 0.697; P = .005] and the Sm < 13.65 cm/s (sensitivity, 66.7%; specificity, 71%; AUC = 0.682; P = .009) combined with elevation of serum hs-cTnT level of 0.0075 ng/mL (sensitivity, 69.2%; specificity, 83.9%; AUC = 0.790; P < .001) after 2-4 chemotherapy cycles from the baseline values can reliably predict cardiotoxicity. CONCLUSIONS: We demonstrated that echocardiographic PW Doppler-derived Tei index, and TDI-derived Sm, combined with serum hs-cTnT level can be obtained in outpatient settings to monitor early cardiac toxicity induced by anthracycline therapy.

Left Ventricular Longitudinal and Circumferential Layer-Specific Myocardial Strains and Their Determinants in Healthy Subjects.

BACKGROUND: The reference values and impact of physiologic variables on echocardiographic quantification of left ventricular (LV) longitudinal and circumferential layer-specific myocardial strains in large series of healthy persons remain unknown. This study prospectively investigated the impact of age, gender, and other physiologic parameters on LV longitudinal and circumferential layer-specific myocardial strains. METHODS: 119 healthy volunteers (age range, 22-76; 50% women) underwent echocardiography. Short-axis (for circumferential strain) and apical (for longitudinal strain) views were analyzed using modified speckle tracking software enabling the analysis of strains in three myocardial layers. RESULTS: In normal subjects, longitudinal and circumferential strain was highest in the endocardium and lowest in the epicardium, longitudinal and circumferential three-layer strain was highest in the apex and lowest in the base. The mean global longitudinal strain in the endocardial layer (GLS-endo), in the mid-myocardial layer (GLS-mid) and in the epicardial layer (GLS-epi) were -24.3 ± 3.1%, -21.3 ± 2.9%, and -18.9 ± 2.8%, respectively. Gender, HR, and SV (stroke volume) were independent predictors of GLS-endo, GLS-mid, and GLS-epi. The mean global circumferential strain in the endocardial layer (GCS-endo), in the mid-myocardial layer (GCS-mid) and in the epicardial layer (GCS-epi) were -34.3 ± 4.4%, -20.5 ± 3.0%, and -11.8 ± 2.7%, respectively. HR independently predicted GCS-endo, GCS-mid, and GCS-epi. CONCLUSIONS: Three-layer analysis of longitudinal and circumferential strain using two-dimensional speckle tracking imaging (2DSTI) can be performed on a clinical basis and may become an important method for the assessment of real time, quantitative global, and regional LV function.

Three-Dimensional Echocardiography in the Evaluation of Right Ventricular Global and Regional Systolic Function in Patients with Atrial Septal Defect before and after Percutaneous Closure.

OBJECTIVE: To evaluate right ventricular (RV) global and regional systolic function in patients with atrial septal defect (ASD) before and after percutaneous closure using real time three-dimensional echocardiography (RT3DE). METHODS: RT3DE was performed in 81 patients with ASD within 24 hours before and after percutaneous closure to obtain RV global and regional ejection fraction (EF) in three compartments (inflow, body, and outflow). RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), peak tricuspid systolic velocity (S), and pulmonary vascular resistance (PVR) were recorded. Forty matched normal adults were included as controls. RESULTS: When compared with controls, RV global and regional EF were decreased in preclosure patients (P < 0.001). FAC was lower while TAPSE and S were higher in preclosure patients than in controls (P < 0.05). After closure, RV systolic function parameters were all reduced (P < 0.001). Regional EF in the body compartment was the lowest among the three compartments in ASD patients (P < 0.05). Procedural percentage changes of RV global EF and regional EF in the inflow compartment were lower than those of two-dimensional systolic function parameters (P < 0.05). RV global and regional EF in the inflow compartment were negatively correlated with PVR in patients after closure (r = -0.601, -0.543, P < 0.001). CONCLUSIONS: RV global and regional systolic functions are impaired in open and closed ASD. RT3DE-derived systolic function parameters are negatively correlated with RV after load. RT3DE has potential value in the evaluation of RV systolic function in patients with ASD.

Prevalence and correlates of mitral regurgitation in the current era: an echocardiography study of a Chinese patient population.

OBJECTIVE: Little is known about the prevalence of mitral regurgitation (MR) in China until now. The objective of the study was to survey the prevalence, correlates and causes of MR in a large Chinese patient population in the current era. METHODS: This study retrospectively analysed the echocardiographic database of the subjects visiting our heart centre from 2010 to 2012. RESULTS: A total of 134,874 cases were included into the analysis. Of these cases 42.44%, 1.63%, 1.44% had mild MR(+), moderate MR(2+) and severe MR(3+/4+), respectively. The rate of MR increased with age. The rate of severe MR was 22.14% in subjects with a left ventricular ejection fraction (LVEF) < 30%, 13.0% in subjects with a LVEF of 30-44%, 15.74% in subjects with left ventricular end-systolic diameter (LVSD) of 50-59 mm, and 27.28% in those with LVSD ≥ 60 mm. The aetiology of 1,948 cases of severe MR was as follows: 972 (49.9%) patients had primary causes, of whom 55 had rheumatic heart disease, 96 had infectious endocarditis, 141 had papillary muscle dysfunction and 608 had degenerative disease, and the other 976 patients had secondary MR. CONCLUSION: MR is common in subjects referring to our heart centre in China. Severe MR is frequent in patients with decreased LVEF or an enlarged left ventricle or atrium. Degenerative disease and secondary changes are the most common causes for severe MR.

[Prevalence and echocardiographic feature of bicuspid aortic valve in patients with severe aortic stenosis: a echocardiography database analysis].

OBJECTIVE: To evaluate the accuracy of echocardiography in identifying aortic valve structures and determine the prevalence of bicuspid aortic valves (BAV) in severe aortic stenosis (AS) population to provide useful information for transcatheteraortic valve replacement (TAVR). METHODS: A total of 300 AS patients undergoing surgical aortic valve replacement were included to determine the accuracy of transthoracic echocardiography in indentifying BAV from January 2009 to July 2013. The echocardiographic data of our hospital from 2004 to 2012 was retrospectively reviewed. 1 371 patients with isolated severe native aortic valves stenosis were consecutively enrolled. RESULTS: The aortic valve structures could be defined by transthoracic echocardiography in 75.7% (227/300) patients with severe AS. With BAV diagnosis during operation as gold standard, the accuracy of transthoracic echocardiography in identifying BAV was 89.4% (203/227). Among 1 371 patients with severe AS, the percentage of BAV in patients aged <40 years, aged 40-59 years, aged 60-69 years, aged 70-79 years and aged ≥ 80 years was 60.0% (57/95), 57.5% (262/456), 42.7% (184/431), 43.2% (133/308) and 21.0% (17/81), respectively. Incidence of BAV in patients with degenerative calcific valve was significant higher than in those with rheumatic heart disease (44.3% (552/1 246) vs. 4.0% (3/76), P<0.01). Proportion of combined aortic regurgitation ≥ grade 2 was significantly lower, ascending aortic diameter was larger and left ventricular end-diastolic dimension was smaller in BAV patients compared to severe AS patients with tricuspid valves (all P<0.01), while aortic valve annuals diameter and accompanying cardiovascular diseases between BAV and tricuspid aortic valve groups were similar (all P>0.05). CONCLUSIONS: Transthoracic echocardiography could accurately identify aortic valve structures in about 76% patients. BAV is common in severe AS patients across all ages. These results provide important information for the popularization of TVAR.

Transcriptomic analysis of differentially expressed genes in the Ras1(CA)-overexpressed and wildtype posterior silk glands.

BACKGROUND: Using the piggyBac-mediated GAL4/UAS transgenic system established in the silkworm, Bombyx mori, we have previously reported that overexpression of the Ras1(CA) oncogene specifically in the posterior silk gland (PSG) improved cell growth, fibroin synthesis, and thus silk yield. However, the detailed molecular mechanism remains to be fully elucidated. To achieve this goal, Illumina sequencing was used in the present study to compare the transcriptomes of the Ras1(CA)-overexpressed and wildtype PSGs. RESULTS: The transcriptomic sequencing results in 56 million reads following filtering steps. Most of the reads (~70%) are successfully mapped to the Bombyx genome. The mapped reads are situated within at least 9,133 predicted genes, covering 62.46% genes of the Bombyx genome. GO annotation shows that 2512 of the 2,636 differentially expressed genes (DEGs) are mostly distributed in metabolic process, cell and cell part, and binding, and KEGG annotation shows that 1,941 DEGs are mapped into 277 pathways. Importantly, Ras1(CA) overexpression in the PSG upregulated many DEGs distributed in "pathways in cancer", "insulin signaling pathway", and "MAPK signaling pathway" as well as "purine metabolism" and "pyrimidine metabolism". Transcriptional regulation of these DEGs was verified by quantitative real-time PCR. Moreover, injection of small-molecule chemical inhibitors of the Ras1 downstream effectors into the Ras1(CA)-overexpressed silkworms revealed that both Raf-MAPK and PI3K-TORC1 pathways are required for the Ras1-induced DEG expression. CONCLUSION: The transcriptomic analysis illustrates that, apart from phosphorylational regulation, Ras1 activates its downstream Raf-MAPK and PI3K-TORC1 pathways at the transcriptional level. Meanwhile, Ras1 increases DNA content and induces endoreplication, at least in part, by upregulating genes in "nucleotide metabolism" and "cell cycle". This study provides further insights into the molecular mechanism of how Ras1(CA) overexpression in the PSG improves silk yield.

Coronary hemodynamic simulation study.

In this paper, a two-way fluid-structure coupling model is developed to simulate and analyze the hemodynamic process based on dynamic coronary angiography, and examine the influence of different hemodynamic parameters on coronary arteries in typical coronary stenosis lesions. Using the measured FFR pressure data of a patient, the pressure-time function curve is fitted to ensure the accuracy of the boundary conditions. The average error of the simulation pressure results compared to the test data is 6.74%. In addition, the results related to blood flow, pressure contour and wall shear stress contour in a typical cardiac cycle are obtained by simulation analysis. These results are found to be in good agreement with the laws of the real cardiac cycle, which verifies the rationality of the simulation. In conclusion, based on the modeling and hemodynamic simulation analysis process of dynamic coronary angiography, this paper proposes a method to assist the analysis and evaluation of coronary hemodynamic and functional parameters, which has certain practical significance.

Cardiac magnetic resonance-based layer-specific strain in immune checkpoint inhibitor-associated myocarditis.

AIMS: To assess the different imaging characteristics between corticosteroid-sensitive (CS) and corticosteroid-refractory (CR) immune checkpoint inhibitor-associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. METHODS AND RESULTS: Thirty-five patients diagnosed with ICIaM and 30 age and gender-matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub-endocardial (GLSendo) and sub-epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non-fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (-14.61 ± 2.67 vs. -18.50 ± 2.53, P < 0.001) and GLSepi (-14.75 ± 2.53 vs. -16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (-16.68 ± 2.05 vs. -19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE-positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189-3.962, P = 0.012). A GLSendo of ≥-17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan-Meier analysis showed that in patients with impaired GLSendo of ≥-17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <-17.10% (Log-rank test P = 0.017). CONCLUSIONS: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid-refractory individuals in the ICIaM population.

Conversion of Polyethylene to High-Yield Fuel Oil at Low Temperatures and Atmospheric Initial Pressure.

The transformation of waste plastics into fuels via energy-efficient and low-cost pyrolysis could incentivize better waste plastic management. Here, we report pressure-induced phase transitions in polyethylene, which continue to heat up without additional heat sources, prompting the thermal cracking of plastics into premium fuel products. When the nitrogen initial pressure is increased from 2 to 21 bar, a monotonically increasing peak temperature is observed (from 428.1 °C to 476.7 °C). At 21 bar pressure under different atmosphere conditions, the temperature change driven by high-pressure helium is lower than that driven by nitrogen or argon, indicating that phase transition is related to the interaction between long-chain hydrocarbons and intercalated high-pressure medium layers. In view of the high cost of high-pressure inert gases, the promotion or inhibition effect of low-boiling hydrocarbons (transitioning into the gaseous state with increasing temperature) on phase transition is explored, and a series of light components are used as phase transition initiators to replace high-pressure inert gases to experiment. The reason that the quantitative conversion of polyethylene to high-quality fuel products is realized through the addition of 1-hexene at a set temperature of 340 °C and the initial atmospheric pressure. This discovery provides a method for recycling plastics by low energy pyrolysis. In addition, we envisage recovering some of the light components after plastic pyrolysis as phase change initiators for the next batch of the process. This method is able to reduce the cost of light hydrocarbons or high-pressure gas insertion, reduce heat input, and improve material and energy utilization.

Effects of Wind-Water Erosion and Topographic Factor on Soil Properties in the Loess Hilly Region of China.

Wind and water erosion processes can lead to soil degradation. Topographic factors also affect the variation of soil properties. The effect of topographic factors on soil properties in regions where wind and water erosion simultaneously occur remains complicated. To address this effect, we conducted this study to determine the relationships between the changes in wind-water erosion and soil properties in different topographic contexts. We collected soil samples from conical landforms with different slope characteristics and positions in the wind-water erosion crisscross region of China. We examined the soil 137Cs inventory, soil organic carbon (SOC), total nitrogen (TN), soil particles, soil water content (SWC), and biomass. 137Cs was applied to estimate soil erosion. The results show that the soil erosion rate followed the order of northwest slope > southwest slope > northeast slope > southeast slope. The soil erosion rate on the northwest slope was about 12.06-58.47% higher than on the other. Along the slopes, the soil erosion rate decreased from the upper to the lower regions, and was 65.65% higher at the upper slope than at the lower one. The change in soil erosion rate was closely related to soil properties. The contents of SOC, TN, clay, silt, SWC, and biomass on the northern slopes (northwest and northeast slopes) were lower than those on the southern slopes (southeast and southwest slopes), and they were lower at the upper slope than at the lower one. Redundancy analysis showed that the variation in soil properties was primarily affected by the slope aspect, and less affected by soil erosion, accounting for 56.1% and 30.9%, respectively. The results demonstrate that wind-water erosion accelerates the impact of topographic factors on soil properties under slope conditions. Our research improves our understanding of the mechanisms of soil degradation in gully regions where wind and water erosion simultaneously occur.

Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response.

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

Evaluation of right ventricular regional volume and systolic function in patients with pulmonary arterial hypertension using three-dimensional echocardiography.

OBJECTIVE: To evaluate right ventricular (RV) regional volume and systolic function in patients with pulmonary arterial hypertension (PAH) using real time three-dimensional echocardiography (RT3DE), and to explore the relationship between parameters measured by RT3DE and right heart catheterization (RHC). METHODS: RT3DE images were acquired from 24 patients with PAH and 27 normal controls for evaluation and analysis to obtain RV regional end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) in three compartments (inflow, body, and outflow). Conventional echocardiographic parameters were calculated and recorded. RHC was performed in 17 patients to obtain pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR). RESULTS: RV regional EDV and ESV were significantly higher while regional EF was significantly lower in the PAH patients when compared with controls (P < 0.001). In the PAH group, EDV was similar in the inflow and body compartment, both higher than that in the outflow compartment (P < 0.05); EF was the highest in the inflow compartment and the lowest in the body compartment (P < 0.05). RV regional EF in the inflow compartment and global EF were negatively correlated with PASP (r =-0.766, -0.816, P < 0.001) and PVR (r =-0.529, -0.656, P < 0.05). CONCLUSIONS: In patients with PAH, RV regional volume was enlarged and systolic function was impaired with distinct characteristics; regional EF in the inflow compartment and global EF were inversely correlated with PASP and PVR. Evaluation of RV regional systolic function using RT3DE may play a potential role in the noninvasive assessment of the severity of PAH.

Catalytic Pyrolysis of Polyethylene for the Selective Production of Monocyclic Aromatics over the Zinc-Loaded ZSM-5 Catalyst.

The transformation of waste plastics into value-added aromatics could incentivize better waste plastic management. The reported studies had low selectivity for monocyclic aromatics because more polycyclic aromatic hydrocarbons and carbon residues were generated. The effects of temperature, pressure, and catalyst on monocyclic aromatic selectivity were explored using a central composite design (CCD) followed by the response surface methodology (RSM) at a high ramp rate of 15 °C/min. The liquid product yield and selectivity to aromatic hydrocarbons were enhanced by regulating the acidic properties of the catalyst and processing parameters. The proportion of monocyclic aromatics in the liquid product was up to 90%, and the yield of monocyclic aromatics based on the reactant mass was 51% at the optimized condition. The carbon deposit production was low (only approximately 1%), which allowed higher liquid yields. In addition, the coupling mechanism of multiple factors on the depolymerization/aromatization reactions was proposed. This conversion of polyethylene into high-yield monocyclic aromatics provides a viable plastic recycling approach.

Pyrolysis of long chain hydrocarbon-based plastics via self-exothermic effects: The origin and influential factors of exothermic processes.

Converting plastic wastes into value-added products through energy-efficient pyrolysis is essential, and it requires lower pyrolysis temperatures and shorter processing times than that of other processes. An exothermic phenomenon was observed during the process high-pressure polyethylene pyrolysis. It was proven for the first time that the exotherm is caused by a pressure-induced phase transition, in which colossal heat release can be driven by relatively small pressures. A large temperature change (> 100 °C) leads to the deep cracking of polyethylene, although the set temperature is far lower than the required temperature for thermal cracking. Importantly, the heat input stops immediately when the set temperature is reached; thus, the external heating time is short. Polyethylene can be completely converted into liquid products in ~90 wt% yield and with a small number of gases. The self-exothermic phase transition only occurs within a certain range of material thickness, which is related to the corresponding phase behavior. In the self-exothermic pyrolysis process, with an increase in the thickness of polyethylene, the proportion of low-value olefins in oil products decreases gradually, while alkanes, isoalkanes and aromatics show an increasing trend, making the product composition closer to the fuel standard. This work provides a viable approach for plastic recycling at low pyrolysis temperatures and short external heating times with the help of a self-exothermic phase transition in the absence of a catalyst.

Identification of early cardiac dysfunction and heterogeneity after pressure and volume overload in mice by high-frequency echocardiographic strain imaging.

Object: Aortic stenosis and regurgitation are clinically important conditions characterized with different hypertrophic types induced by pressure or volume overload, respectively, but with comparable cardiac function in compensated stage. Speckle-tracking based strain imaging has been applied to assess subtle alterations in cardiac abnormality, but its application in differentiating these two types of ventricular hypertrophy is still sparse. Here, we performed strain imaging analysis of cardiac remodeling in these two loading conditions. Methods: C57BL/6J mice were subjected to transverse aortic constriction (TAC)-induced pressure overload or aortic regurgitation (AR)-induced volume overload. Conventional echocardiography and strain imaging were comprehensively assessed to detect stimulus-specific alterations in TAC and AR hearts. Results: Conventional echocardiography did not detect significant changes in left ventricular systolic (ejection fraction and fractional shortening) and diastolic (E/E') function in either TAC or AR mice. On the contrary, global strain analysis revealed global longitudinal strain and strain rate were remarkably impaired in TAC while preserved in AR mice, although global radial, and circumferential strain and strain rate were significantly reduced in both models. Regional strain analysis in the long axis demonstrated that longitudinal strain and strain rate in all or most segments were decreased in TAC but maintained or slightly dented in AR mice, while radial strain and strain rate indicated overt decline in both models. Moreover, decreased radial and circumferential strain and strain rate were observed in most segments of TAC and AR mice in the short axis. Conclusion: Strain imaging is superior to conventional echocardiography to detect subtle changes in myocardial deformation, with longitudinal strain and strain rate indicating distinct functional changes in pressure versus volume overload myocardial hypertrophy, making it potentially an advanced approach for early detection and differential diagnosis of cardiac dysfunction.

Protective Effect of Crocin on Immune Checkpoint Inhibitors-Related Myocarditis Through Inhibiting NLRP3 Mediated Pyroptosis in Cardiomyocytes via NF-κB Pathway.

Purpose: Immune checkpoint inhibitors (ICIs)-related myocarditis is now one of the most critical immune-related adverse effects (irAEs) in tumor immunotherapy, which has raised great concern in cardio-oncology. The pathogenesis involved in cardiac injury remains elusive. Crocin, the main component of saffron, has shown distinct functions in cardioprotective and anti-inflammation properties. We therefore aimed to investigate the potential effect of crocin on the protection of ICIs-related myocarditis and its underlying molecular mechanism. Methods: We immunized the BALB/c mice with murine cardiac troponin I (cTnI) peptide and additionally gave anti-mouse programmed death 1 (PD-1) to induce the mouse model of ICIs-related myocarditis. Mice were treated with crocin at different dosages. In vitro, HL-1 cells were pre-incubated with crocin at different concentrations and then stimulated with lipopolysaccharide (LPS). Myocardial contractile functions, myocardial inflammation and fibrosis, and myocardial injury were assessed. The expressions of pyroptosis-related proteins and nuclear factor-κB (NF-κB) pathway were evaluated. Results: Crocin treatment could partially reverse the ICIs-related myocarditis in terms of improving heart function, ameliorating inflammation and fibrosis in the myocardium, and alleviating myocardial injury. Mechanistically, ICIs administration significantly activated pyrin domain-containing protein 3 (NLRP3) inflammasome in cardiomyocytes. Crocin treatments significantly downregulated the expression of NLRP3, cleaved gasdermin D (GSDMD), cleaved caspase1, interleukin-1ß (IL-1ß), and IL-18. Besides, crocin inhibited the activation of NF-κB pathway, which performed as reducing the phosphorylation of p-NF-kappa-B inhibitor-α (p-IκBα), degradation of IκBα, phosphorylation of p65 and p65 DNA binding activity both in vivo and in vitro. Conclusion: By reversing the pyroptosis in cardiomyocytes, crocin treatment in a mouse model exerted great potential to aid in the prevention of ICIs-related myocarditis from a novel target.