The Preliminary Analysis of Flavonoids in the Petals of Rhododendron delavayi, Rhododendron agastum and Rhododendron irroratum Infected with Neopestalotiopsis clavispora.

The petal blight disease of alpine Rhododendron severely impacts the ornamental and economic values of Rhododendron. Plant secondary metabolites play a crucial role in resisting pathogenic fungi, yet research on metabolites in alpine Rhododendron petals that confer resistance to pathogenic fungi is limited. In the present study, the secondary metabolites in Rhododendron delavayi, R. agastum, and R. irroratum petals with anti-pathogenic activity were screened through disease index analysis, metabolomic detection, the mycelial growth rate, and metabolite spraying experiments. Disease index analysis revealed that R. delavayi petals exhibited the strongest disease resistance, while R. agastum showed the weakest, both under natural and experimental conditions. UHPLC-QTOF-MS/MS analysis identified 355 and 274 putative metabolites in positive and negative ion modes, respectively. The further antifungal analysis of differentially accumulated baicalein, diosmetin, and naringenin showed their half-inhibitory concentrations (IC50) against Neopestalotiopsis clavispora to be 5000 mg/L, 5000 mg/L, and 1000 mg/L, respectively. Spraying exogenous baicalein, diosmetin, and naringenin significantly alleviated petal blight disease caused by N. clavispora infection in alpine Rhododendron petals, with the inhibition rates exceeding 64%. This study suggests that the screened baicalein, diosmetin, and naringenin, particularly naringenin, can be recommended as inhibitory agents for preventing and controlling petal blight disease in alpine Rhododendron.

Comparative study on metabolites, nutrients, and antioxidant capacity of endosperm in Gymnocladus chinensis, Gleditsia sinensis, and Gleditsia japonica var. delavayi.

'Zaojiaomi' is a traditional food derived from Gleditsia sinensis or Gleditsia japonica var. delavayi endosperm. However, metabolite profile of Gymnocladus chinensis endosperm and its comparison to the aforementioned species remains understudied. This research employed a UPLC-MS based metabolomics approach to investigate and compare metabolite composition of G. chinensis endosperm with that of G. sinensis and G. japonica endosperm. A total of 1177 metabolites were identified, with 579 and 577 differentially abundant metabolites found between G. chinensis vs. G. japonica and G. chinensis vs. G. sinensis, respectively. They were mainly enriched in pathways related to flavonoid biosynthesis, suggesting potential for enhanced antioxidant activity, compared to G. japonica and G. sinensis. Additionally, G. chinensis endosperm was found to be rich in L-arginine, L-aspartic acid, and zinc elements, which have various health benefits. These findings provide valuable insights into metabolic composition of G. chinensis endosperm and its potential as a functional food source.

Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Pulmonary vascular resistance predicts the mortality in patients with bronchiectasis-associated pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension is a severe complication of bronchiectasis, characterized by elevated pulmonary vascular resistance (PVR) and subsequent right heart failure. The association between PVR and mortality in bronchiectasis-associated pulmonary hypertension has not been investigated previously. METHODS: In the present study, a retrospective analysis was conducted on 139 consecutive patients diagnosed with bronchiectasis-associated pulmonary hypertension based on right heart catheterization, enrolled between January 2010 and June 2023. Baseline clinical characteristics and hemodynamic assessment were analyzed. The survival time for each patient was calculated in months from the date of diagnosis until the date of death or, if the patient was still alive, until their last visit. RESULTS: Patients with bronchiectasis-associated pulmonary hypertension exhibited estimated survival rates of 89.5, 70, and 52.9 at 1-year, 3-year, and 5-year intervals respectively, with a median survival time of 67 months. Multivariable Cox regression analysis revealed that increased age [(adjusted hazard ratio per year 1.042, 95% confidence interval (CI) 1.008-1.076, P  = 0.015] and elevated PVR (adjusted HR per 1 Wood Units 1.115, 95% CI 1.015-1.224, P  = 0.023) were associated with an increased risk of all-cause mortality. In contrast, higher BMI was associated with a decreased risk of all-cause death (adjusted hazard ratio per 1 kg/m 2 0.915, 95% CI 0.856-0.979, P  = 0.009). Receiver-operating characteristic analyses identified a cutoff value for PVR at 4 Wood Units as predictive for all-cause death within 3 years [area under the curve (AUC) = 0.624; specificity= 87.5%; sensitivity= 35.8%; P  < 0.05]. Patients with a PVR greater than 4 Wood Units had a significantly higher risk of all-cause death compared with those with 4 Wood Units or less (adjusted hazard ratio 2.392; 95% CI 1.316-4.349; P  = 0.019). Notably, there were no significant differences in age, sex, BMI, WHO functional class, 6-min walk distance, and NT-proBNP levels at baseline between patients categorized as having 4 Wood Units or less or greater than 4 Wood Units for PVR. CONCLUSION: Based on these data, PVR could serve as a discriminative marker for distinguishing between nonsevere pulmonary hypertension (PVR ≤ 4 Wood Units) and severe pulmonary hypertension (PVR > 4 Wood Units). The utilization of a PVR cutoff value of 4.0 Wood Units provides enhanced prognostic capabilities for predicting mortality.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Ultra-compact exciton polariton modulator based on van der Waals semiconductors.

With the rapid emergence of artificial intelligence (AI) technology and the exponential growth in data generation, there is an increasing demand for high-performance and highly integratable optical modulators. In this work, we present an ultra-compact exciton-polariton Mach-Zehnder (MZ) modulator based on WS2 multilayers. The guided exciton-polariton modes arise in an ultrathin WS2 waveguide due to the strong excitonic resonance. By locally exciting excitons using a modulation laser in one arm of the MZ modulator, we induce changes in the effective refractive index of the polariton mode, resulting in modulation of transmitted intensity. Remarkably, we achieve a maximum modulation of -6.20 dB with an ultra-short modulation length of 2 µm. Our MZ modulator boasts an ultra-compact footprint area of ~30 µm² and a thin thickness of 18 nm. Our findings present new opportunities for the advancement of highly integrated and efficient photonic devices utilizing van der Waals materials.

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein-protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-ß1 (TGF-ß1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Idiopathic pulmonary hypertension (IPAH) is a rare and devastating disease often accompanied by persistent inflammation and immune responses. We aim to provide a reference atlas of neutrophils to facilitate a better understanding of cellular phenotypes and discovery of candidate genes. METHODS: Peripheral neutrophils from naive patients with IPAH and matched controls were profiled. Whole-exon sequencing was performed to exclude known genetic mutations before establishing single-cell RNA sequencing. Marker genes were validated by flow cytometry and histology in a separate validation cohort. RESULTS: Seurat clustering analysis revealed that the landscape of neutrophils encompassed 5 clusters, including 1 progenitor, 1 transition, and 3 functional clusters. The intercorrelated genes in patients with IPAH were mainly enriched in antigen processing presentation and natural killer cell mediated cytotoxicity. We identified and validated differentially upregulated genes, including MMP9 (matrix metallopeptidase 9), ISG15 (ISG15 ubiquitin-like modifier), and CXCL8 (C-X-C motif ligand 8). The positive proportions and fluorescence quantification of these genes were significantly increased in CD16+ neutrophils in patients with IPAH. The higher proportion of positive MMP9 neutrophils increased mortality risk after adjustment for age and sex. Patients with higher proportions of positive MMP9 neutrophils had worse survival, while the fraction of ISG15- or CXCL8-positive expression neutrophils failed to predict outcome. CONCLUSIONS: Our study yields a comprehensive dataset of the landscape of neutrophils in patients with IPAH. The predictive values of a neutrophil cluster characterized by higher MMP9 expression indicate a functional role for neutrophil-specific matrix metalloproteinases in the pathogenesis of pulmonary arterial hypertension.

Electric-Field-Driven Trion Drift and Funneling in MoSe2 Monolayer.

Excitons, electron-hole pairs in semiconductors, can be utilized as information carriers with a spin or valley degree of freedom. However, manipulation of excitons' motion is challenging because of their charge-neutral characteristic and short recombination lifetimes. Here we demonstrate electric-field-driven drift and funneling of charged excitons (i.e., trions) toward the center of a MoSe2 monolayer. Using a simple bottom-gate device, we control the electric fields in the vicinity of the suspended monolayer, which increases the trion density and pulls down the layer. We observe that locally excited trions are subjected to electric force and, consequently, drift toward the center of the stretched layer. The exerting electric force on the trion is estimated to be 102-104 times stronger than the strain-induced force in the stretched monolayer, leading to the successful observation of trion drift under continuous-wave excitation. Our findings provide a new route for manipulating trions and achieving new types of optoelectronic devices.

Differences in disease severity and prognosis of exercise-induced right-to-left shunt between idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients.

Objective: Whether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS. Methods: We conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients. Results: Exercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival. Conclusion: Exercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.

Efficacy and safety of switching from bosentan or ambrisentan to macitentan in pulmonary arterial hypertension: A systematic review and meta-analysis.

Background: There is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan. Methods: We retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival. Results: Nine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, P < 0.00001, I 2 = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, P = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated. Conclusion: The switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].

Sex-specific differences in sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary hypertension and chronic thromboembolic pulmonary disease.

Objective: Although chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are known to be accompanied by symptoms associated with sleep-disordered breathing (SDB) and nocturnal hypoxemia, the sex-specific differences of SDB and nocturnal hypoxemia in patients with CTEPH and CTEPD remain unknown. Methods: Between July 2020 and August 2022, data were retrieved from 57 males and 63 female patients with CTEPH and CTEPD who underwent sleep study at Shanghai Pulmonary Hospital. Nocturnal mean SpO2 (mean SpO2) < 90% was defined as nocturnal hypoxemia. Logistic and linear regression analysis was performed to assess the predictive value of sleep study indices to hemodynamic parameters. Receiver operating characteristic (ROC) curve was applied to analyze the specific parameters to predict the risk of CTEPH. Results: SDB was similarly present in males and females, and both sexes predominantly had obstructive sleep apnea (OSA); more women were diagnosed with nocturnal hypoxemia (32 vs. 7%, p = 0.002). SaO2 was negatively associated with mean pulmonary arterial pressure (mPAP) in men (p < 0.001), whereas the ratio of nocturnal SpO2 < 90% of the total monitoring time (T90%) was positively correlated with mPAP. Mean SpO2 was an independent predictor for pulmonary vascular resistance and cardiac output in women (p = 0.001, p < 0.001, p = 0.001, respectively). T90%, SaO2, and minimal SpO2 were combined to develop a new composite parameter: hypoxemia scoring index (HSI). ROC curve analysis indicated that HSI levels of 0.55 could discriminate CTEPH from CTEPD with a sensitivity of 92.3% and specificity of 87.5% in female patients (an area under the curve, 0.937; 95% CI: 0.879-0.995, p < 0.001). Conclusion: Sex-specific nocturnal hypoxemia was present in patients with CTEPH or CTEPD. In female patients, the HSI showed high capacity for predicting the risk of CTEPH. Clinical trials registration: Registry: chictr.org.cn; Identifier: ChiCTR-DDD-16009406.

Long-term outcomes in health-related quality of life influence chronic disease management in patients with pulmonary hypertension.

Background: Significantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes. Methods: A total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups. Results: Patients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up. Conclusion: Patients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.

Direct Observation of Self-Hybridized Exciton-Polaritons and Their Valley Polarizations in a Bare WS2 Layer.

The strong excitonic properties of transition metal dichalcogenides (TMD) have led to the successful demonstration of exciton-polaritons (EPs) in various optical cavity structures. Recently, self-hybridized EPs have been discovered in a bare TMD layer, but experimental investigation is still lacking because of their nonradiative nature. Herein, the direct observation of self-hybridized EPs in a bare multilayer WS2 via the evanescent field coupling technique is reported. Because of the thickness-dependent Rabi splitting energy, the dispersion curves of the EPs change sensitively with sample thickness. Moreover, continuous tuning of EP dispersion curves is demonstrated by controlling the excitation laser power. Lastly, it is observed that guided EPs retain valley polarization up to 0.2 at room temperature, representing a valley-preserved strong coupling regime. It is believed that the high tunability and valley polarization properties of the guided EPs in bare TMD layers can facilitate new nanophotonic and valleytronic applications.

A Study of the Efficacy and Safety of Aerobic Exercise Training in Pulmonary Arterial Hypertension (the Saturday Study): Protocol for a Prospective, Randomized, and Controlled Trial.

Background: Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation in PAH results in clinically relevant improvements in exercise capacity and hemodynamics. To clarify the mechanism, we will evaluate the effect of aerobic exercise training rehabilitation on right ventricular (RV) remodeling and function as determined measured by cardiac magnetic resonance imaging (CMR). Methods: We will conduct a 26-week multicenter randomized controlled trial. Patients on stable and unchanged PAH-targeted medication are randomly assigned (1:1) to the control and training groups. The primary endpoint is the RV stroke volume (RVSV) change from baseline to Week 26, determined by CMR. Comprehensive RV function is also performed using CMR. Other characteristics of the RV and left ventricle, World Health Organization functional class, 6-min walk distance, and N-terminal pro-B-type natriuretic peptide are included in secondary endpoints. We also investigate the proteomic, metabolomic, and transcriptomic changes after exercise training as exploratory endpoints. Ethics and Dissemination: The study and protocol were approved by the Ethics Committee of Shanghai Pulmonary Hospital (Approved No. of ethics committee: L20-17). The results will be disseminated at medical conferences and in journal publications. All participants will sign written informed consent. Trial Registration Number: ChiCTR2000031650.

Peak oxygen uptake is a strong prognostic predictor for pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD. METHODS: A single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan-Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death. RESULTS: Seventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO2)/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni's correction. Multivariate Cox regression revealed that the peak VO2/kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO2/kg ≥ 10.7 ml kg-1 min-1, Ipc-PH patients with a peak VO2/kg < 10.7 ml kg-1 min-1 had a worse survival (P < 0.001). CONCLUSIONS: The peak VO2/kg is independently associated with all-cause death in patients with PH-LHD. The peak VO2/kg can also be analyzed together with Cpc-PH/Ipc-PH to better indicate the prognosis of patients with PH-LHD.

The Role of Glutamine and Glutaminase in Pulmonary Hypertension.

Pulmonary hypertension (PH) refers to a clinical and pathophysiological syndrome in which pulmonary vascular resistance and pulmonary arterial pressure are increased due to structural or functional changes in pulmonary vasculature caused by a variety of etiologies and different pathogenic mechanisms. It is followed by the development of right heart failure and even death. In recent years, most studies have found that PH and cancer shared a complex common pathological metabolic disturbance, such as the shift from oxidative phosphorylation to glycolysis. During the shifting process, there is an upregulation of glutamine decomposition driven by glutaminase. However, the relationship between PH and glutamine hydrolysis, especially by glutaminase is yet unclear. This review aims to explore the special linking among glutamine hydrolysis, glutaminase and PH, so as to provide theoretical basis for clinical precision treatment in PH.

Echocardiography Nomogram for Predicting Survival among Chronic Lung Disease Patients with Severe Pulmonary Hypertension.

Severe pulmonary hypertension in chronic lung diseases (severe CLD-PH) differs significantly from other types of PH in physiology and prognosis. We aimed to assess whether echocardiography helps predict long-term survival in patients with severe CLD-PH. This single-centre, observational cohort study enrolled 100 patients with severe CLD-PH (mean pulmonary arterial pressure ≥35 mm Hg or ≥25 mm Hg with cardiac index <2.0 L/min/m2 or pulmonary vascular resistance ≥6 Wood units) between 2009 and 2014. The population was randomly divided into a derivation and validation cohort in a 2:1 ratio. To construct a nomogram, a multivariable logistic regression model was applied, and scores were assigned based on the hazard ratio of independent echocardiographic predictors. Multivariate Cox hazards analysis identified the strongest predictors of mortality as pulmonary arterial systolic pressure (PASP), tricuspid annular plane systolic excursion, and right ventricular end-diastolic transverse dimension. The three independent predictors were entered into the nomogram. Compared with PASP alone, the nomogram resulted in an integrated discrimination improvement of 15.5% (95% confidence interval, 5.52−25.5%, p = 0.002) with a net improvement in model discrimination (C-statistic from 0.591 to 0.746). Using echocardiographic parameters, we established and validated a novel nomogram to predict all-cause death for patients with severe CLD-PH.