Aptamer Conjugate-Based Ratiometric Fluorescent Probe for Precise Imaging of Therapy-Induced Cancer Senescence.

Therapy-induced cellular senescence has been increasingly recognized as a key mechanism to promote various aspects of carcinogenesis in a nonautonomous manner. Thus, real-time imaging monitoring of cellular senescence during cancer therapy is imperative not only to further elucidate its roles in cancer progression but also to provide guidance for medical management of cancer. However, it has long been a challenging task due to the lack of effective imaging molecule tools with high specificity and accuracy toward cancer senescence. Herein, we report the rational design, synthesis, and evaluation of an aptamer conjugate-based ratiometric fluorescent probe for precise imaging of therapy-induced cancer senescence. Unlike traditional senescence imaging systems, our probe targets two senescence-associated markers at both cellular and subcellular dimensions, namely, aptamer-mediated membrane marker recognition for active cell targeting and lysosomal marker-triggered ratiometric fluorescence changes of two cyanine dyes for site-specific, high-contrast imaging. Moreover, such a two-channel fluorescence response is activated after a one-step reaction and at the same location, avoiding the diffusion-caused signal decay previously encountered in dual-marker activated probes, contributing to spatiotemporally specific imaging of therapy-induced cancer senescence in living cells and three-dimensional multicellular tumor spheroids. This work may offer a valuable tool for a basic understanding of cellular senescence in cancer biology and interventions.

The serine protease 2 gene regulates lipid metabolism through the LEP/ampkα1/SREBP1 pathway in bovine mammary epithelial cells.

Molecular breeding has brought about significant transformations in the milk market and production system during the twenty-first century. The primary economic characteristic of dairy production pertains to milk fat content. Our previous transcriptome analyses revealed that serine protease 2 (PRSS2) is a candidate gene that could impact milk fat synthesis in bovine mammary epithelial cells (BMECs) of Chinese Holstein dairy cows. To elucidate the function of the PRSS2 gene in milk fat synthesis, we constructed vectors for PRSS2 overexpression and interference and assessed intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified fatty acid (NEFA) contents in BMECs. Fatty acid varieties and components were also quantified using gas chromatography‒mass spectrometry (GC‒MS) technology. The regulatory pathway mediated by PRSS2 was validated through qPCR, ELISA, and WB techniques. Based on our research findings, PRSS2 emerges as a pivotal gene that regulates the expression of associated genes, thereby making a substantial contribution to lipid metabolism via the leptin (LEP)/Adenylate-activated protein kinase, alpha 1 catalytic subunit (AMPKα1)/sterol regulatory element binding protein 1(SREBP1) pathway by inhibiting TGs and CHOL accumulation while potentially promoting NEFA synthesis in BMECs. Furthermore, the PRSS2 gene enhances intracellular medium- and long-chain fatty acid metabolism by modulating genes related to the LEP/AMPKα1/SREBP1 pathway, leading to increased contents of unsaturated fatty acids C17:1N7 and C22:4N6. This study provides a robust theoretical framework for further investigation into the underlying molecular mechanisms through which PRSS2 influences lipid metabolism in dairy cows.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Effects of malnutrition on disease severity and adverse outcomes in idiopathic pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.

Flotation Separation of Fluorite from Calcite using an Efficient Depressant Nitrilotriacetic Acid in the NaOL System.

Fluorite and calcite were separated with nitrilotriacetic acid (NTA) as a depressant. The single mineral flotation experiment confirmed that with 40 mg/L NaOL and 80 mg/L NTA, the fluorite recovery and calcite recovery were 24.37 and 94.13%, respectively, at pH 9. Meanwhile, in the fluorite-calcite binary mixed ore flotation experiment, the calcite recovery and fluorite recovery were 75.50 and 26.84%, respectively, and the CaCO3 and CaF2 grade in concentrate was 74.32 and 25.61%, respectively. The results confirmed that NTA could be used as a depressant to selectively inhibit fluorite flotation. The mechanism study illustrated that NTA was selectively reacted with fluorite by chemical interaction between O of NTA and Ca of fluorite. The adsorption of NTA on fluorite will impede the interaction between fluorite and NaOL. NTA could adsorb on fluorite in three ways, while the dominant two ways were the complex between double O of NTA and Ca of fluorite in a vertical model and the complex between double O of NTA and Ca of fluorite in a horizontal model.

Intelligent Gas Detection: g-C3N4/Polypyrrole Decorated Alginate Paper as Smart Selective NH3/NO2 Sensors at Room Temperature.

Chemiresistive NH3/NO2 sensors are attracting considerable attention for use in air-conditioning systems. However, the existing sensors suffer from cross-sensitivity, detection limit, and power consumption, owing to the inadequate charge-transfer ability of gas-sensing materials. Herein, we develop a flexible NH3/NO2 sensor based on graphitic carbon nitride/polypyrrole decorated alginate paper (AP@g-CN/PPy). The flexible sensor can work at room temperature and exhibits a positive response of 23-246% and a negative response of 37-262% toward 0.1-5 ppm of NH3 and NO2, which is ∼4.5 times and ∼7.0 times higher than a pristine PPy sensor. Moreover, the sensor exhibits flexibility, reproducibility, long-term stability, anti-interference, and high resilience to humidity, indicating its promising potential in real applications. Using the 9 feature parameters extracted from the transient response, a matched deep learning model was developed to achieve qualitative recognition of different types of gases with distinguished decision boundaries. This work not only provides an alternative gas-sensing material for dual NH3/NO2 sensing but also establishes an intelligent strategy to identify hazardous gases under an interfering atmosphere.

In Situ Creation of Surface Defects on Pd@NiPd with Core-shell Hierarchical Structure Toward Boosting Electrocatalytic Activity.

A deep insight into surface structural evolution of the catalyst is a challenging issue to reveal the structure-activity relationship. In this contribution, based on a surface alloying strategy, the dual-functional Pd@NiPd catalyst with a unique core-shell hierarchical structure is developed through selective crystal growth, surface cocrystallization, directional self-assembly, and reduction process. The surface defects are created in situ on the outer NiPd alloy layer in the electrochemical redox processes, which endow the Pd@NiPd catalyst with excellent electrocatalytic activity of hydrogen generation reaction (HER) and oxygen generation reaction (OER) in alkaline media. The optimal Pd@NiPd-2 catalyst requires an overpotential of only 18 mV that is far lower than Pt/C benchmark (43 mV) at the current density of 10 mA cm-2 for the HER, and 210 mV that is far lower than RuO2 benchmark (430 mV) at 50 mA cm-2 for the OER. Density functional theory (DFT) calculations reveal that the outstanding electrocatalytic activity is originated from the creation of surface defect structure that induces a significant reduction in the adsorption and dissociation energy barriers of H2O molecules in the HER and a decrease in the conversion energy from O* to OOH* that resulted from the synergy of two adjacent Pd sites by forming O-bridge. This work affords a typical paradigm for exploiting efficient catalysts and investigating the dependence of electrocatalytic activity on the surface structural evolution.

Nomogram for hospital-acquired venous thromboembolism among patients with cardiovascular diseases.

BACKGROUND: Identifying venous thromboembolism (VTE) is challenging for patients with cardiovascular diseases due to similar clinical presentation. Most hospital-acquired VTE events are preventable, whereas the implementation of VTE prophylaxis in clinical practice is far from sufficient. There is a lack of hospital-acquired VTE prediction models tailored specifically designed for patients with cardiovascular diseases. We aimed to develop a nomogram predicting hospital-acquired VTE specifically for patients with cardiovascular diseases. MATERIAL AND METHODS: Consecutive patients with cardiovascular diseases admitted to internal medicine of Fuwai hospital between September 2020 and August 2021 were included. Univariable and multivariable logistic regression were applied to identify risk factors of hospital-acquired VTE. A nomogram was constructed according to multivariable logistic regression, and internally validated by bootstrapping. RESULTS: A total of 27,235 patients were included. During a median hospitalization of four days, 154 (0.57%) patients developed hospital-acquired VTE. Multivariable logistic regression identified that female sex, age, infection, pulmonary hypertension, obstructive sleep apnea, acute coronary syndrome, cardiomyopathy, heart failure, immobility, central venous catheter, intra-aortic balloon pump and anticoagulation were independently associated with hospital-acquired VTE. The nomogram was constructed with high accuracy in both the training set and validation (concordance index 0.865 in the training set, and 0.864 in validation), which was further confirmed in calibration. Compared to Padua model, the Fuwai model demonstrated significantly better discrimination ability (area under curve 0.865 vs. 0.786, net reclassification index 0.052, 95% confidence interval 0.012-0.091, P = 0.009; integrated discrimination index 0.020, 95% confidence interval 0.001-0.039, P = 0.051). CONCLUSION: The incidence of hospital-acquired VTE in patients with cardiovascular diseases is relatively low. The nomogram exhibits high accuracy in predicting hospital-acquired VTE in patients with cardiovascular diseases.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Circulating acetylcholine serves as a potential biomarker role in pulmonary hypertension.

BACKGROUND: An increased acetylcholine (ACh) level in the right ventricle tissue of pulmonary hypertension (PH) was revealed, which indicated the important role of ACh in disease pathogenesis. However, the relationship between plasma ACh levels and disease conditions and patients' prognosis has not been investigated. We aimed to explore the association between plasma ACh levels and the prognosis of patients with PH. We also discussed the feasibility of plasma ACh as a biomarker, which may contribute to the management of PH patients in the future. METHODS: Patients with confirmed PH in Fuwai Hospital from April 2019 to August 2020 were enrolled. The primary clinical outcome in this study was defined as a composite outcome, including death/lung transplantation, heart failure, and worsening of symptoms. Fasting plasma was collected to detect the ACh levels. The association between ACh levels and patients' prognosis was explored. RESULTS: Finally, four hundred and eight patients with PH were enrolled and followed for a mean period of 2.5 years. Patients in the high ACh group had worse World Health Organization Functional Class (WHO-FC), lower 6-minute walk distance (6 MWD), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP). Notably, echocardiographic and hemodynamic parameters in the high metabolite group also suggested a worse disease condition compared with the low ACh group. After adjusting for confounders, compared with low ACh patients, those with high metabolite levels still have worse prognoses characterized as elevated risk of mortality, heart failure, and symptoms worsening. CONCLUSION: High circulating ACh levels were associated with severe PH conditions and poor prognosis, which might serve as a potential biomarker in PH.

The Complement Component 4 Binding Protein α Gene: A Versatile Immune Gene That Influences Lipid Metabolism in Bovine Mammary Epithelial Cell Lines.

Complement component 4 binding protein α (C4BPA) is an immune gene which is responsible for the complement regulation function of C4BP by binding and inactivating the Complement component C4b (C4b) component of the classical Complement 3 (C3) invertase pathway. Our previous findings revealed that C4BPA was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a C4BPA gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of C4BPA in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased (p < 0.05) after knocking out C4BPA in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the C4BPA gene was knocked out. Collectively, C4BPA gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.

Room-Temperature Optoelectronic Gas Sensor Based on Core-Shell g-C3N4@WO3 Heterocomposites for Efficient Ammonia Detection.

The ever-growing modern industry promotes the evolution of gas sensors for environmental monitoring and safety inspection. However, traditional chemiresistive gas sensors still suffer from drawbacks of high power consumption and detection limit, mainly due to the insufficient charge-transfer ability of gas-sensing materials. Here, an optoelectronic gas sensor that can detect ppb-level ammonia at room temperature is constructed based on core-shell g-C3N4@WO3 heterocomposites. The growth of WO3 nanosheets on graphitic g-C3N4 nanosheets was precisely controlled, achieving well-defined g-C3N4@WO3 core-shell architectures. Based on the synergism between light activation and the amplification effect of in situ-formed heterojunctions, the g-C3N4@WO3 sensor exhibits improved sensing characteristics for reliable ammonia detection. As compared with the pristine g-C3N4 sensor, the sensor response toward ammonia is enhanced 21 times and the detection limit is reduced from 308 to 108 ppb. This work provides a successful approach for the in situ formation of core-shell g-C3N4@WO3 interfacial composites and offers an easy solution for the rational design of advanced optoelectronic gas sensors.

Development and Validation of a Nomogram for Balloon Pulmonary Angioplasty-Related Complications in Patients with Chronic Thromboembolic Pulmonary Hypertension.

Background: Balloon pulmonary angioplasty (BPA)-related complications are not uncommon and could contribute to perioperative mortality. However, there is a lack of a prediction model for BPA-related complications. Methods: Data from consecutive patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) who underwent BPA were retrospectively analyzed. The primary outcome was BPA-related complications. The secondary outcomes were mortality and hemodynamics after BPA. Results: A total of 207 patients with 614 BPA sessions were included. Complications occurred during 63 sessions (10.26%) in 49 patients. Hemoptysis or hemosputum (6.51%) was the most common complication, whereas pulmonary reperfusion edema was rare (0.49%). Multivariable logistic regression identified that disease duration, mean pulmonary arterial pressure (mPAP) and the proportion of occlusion lesions were correlated with BPA complications. A nomogram was constructed accordingly, which had the highest area under curve (0.703) and was superior to previously reported predictors [nomogram vs. mPAP, net reclassification index (95% confidence interval (CI)), 0.215 (0.002, 0.427), p = 0.047; integrated discrimination index (95% CI), 0.059 (0.010, 0.109), p = 0.018]. The nomogram was found to be accurate based on validation and calibration (slope 0.978, Bier score 0.163). After adjusting for the number of BPA sessions in multivariable linear regression, the occurrence of complications was not associated with hemodynamic improvement after BPA. The 3-year survival was also comparable between patients with and without complications (98.0% vs. 94.8%, log-rank p = 0.503). Conclusions: The nomogram, comprising mPAP, the proportion of occlusion lesions and disease duration, could better predict BPA-related complications than previously reported single parameters. Distinctively, the occurrence of complications did not impair the beneficial impact of BPA on hemodynamics and survival. The occurrence of complications should not discourage patients from continuing BPA sessions.

Fabrication and Characterization of Carrageenan/ZnO/Chitosan Composite Films.

In this study, a high-performance carrageenan/ZnO/chitosan composite film (FCA/ZnO/CS) was fabricated by the solution/dispersion casting method and layer-by-layer method. The first layer was nano-ZnO dispersed in carrageenan solution, and the second layer was chitosan dissolved in acetic acid. The morphology, chemical structure, surface wettability, barrier properties, mechanical properties, optical properties, and antibacterial activity of FCA/ZnO/CS were evaluated compared with a carrageenan film (FCA) and carrageenan/ZnO composite film (FCA/ZnO). This study revealed that the Zn element in FCA/ZnO/CS existed in the form of Zn2+ in FCA/ZnO/CS. There existed electrostatic interaction and hydrogen bonding between CA and CS. As a result, the mechanical strength and transparency of FCA/ZnO/CS were enhanced and the water vapor transmittance of FCA/ZnO/CS was decreased compared with that of FCA/ZnO. Furthermore, the addition of ZnO and CS greatly enhanced the antibacterial activity of Escherichia coli and also had a certain inhibitory effect on Staphylococcus aureus. FCA/ZnO/CS is expected to be a potential candidate material for food packaging, wound dressings, and various surface antimicrobial coatings.

Recent advances in the combinations of plant-sourced natural products for the prevention of mycotoxin contamination in food.

Mycotoxins, secondary metabolites produced by mycotoxigenic fungi, are a major problem affecting food safety and security, because of their adverse health effects, their socio-economic impact and the difficulty of degradation or removal by conventional food processing methods. Plant-sourced natural products are a novel and effective control method for fungal infestation and mycotoxin production, with the advantages of biodegradability and acceptability for food use. However, development of resistance, low and inconsistent efficacy, and a limited range of antifungal activities hinder the effective application of single plant natural products for controlling mycotoxin contamination. To overcome these limitations, combinations of plant natural products have been tested extensively and found to increase efficacy, often synergistically. However, this extensive and promising research area has seen little development of practical applications. This review aims to provide up-to-date information on the antifungal, anti-mycotoxigenic and synergistic effects of combinations of plant natural products, as well as their mechanisms of action, to provide a reference source for future research and encourage application development.

Circulating choline levels are associated with prognoses in patients with pulmonary hypertension: a cohort study.

BACKGROUNDS: Mounting evidences have highlighted the association between metabolites and cardiovascular diseases. Our previous works have demonstrated that circulating metabolite, trimethylamine oxide, was associated with prognosis of patients with pulmonary hypertension (PH). Choline is a precursor of trimethylamine oxide and its role in PH remains unknown. Here, we aimed to validate the hypothesis that circulating choline levels were associated with prognoses in patients with PH. METHODS: Inpatients diagnosed with PH-defined as mean pulmonary arterial pressure ≥ 25 mmHg by right heart catheterisation-from Fuwai Hospital were enrolled after excluding relative comorbidities. Fasting blood samples were obtained to assess choline levels and other clinical variables. The primary endpoints were defined as death, escalation of targeted medication, rehospitalization due to heart failure, PH deterioration. The follow-up duration was defined as the time from the choline examination to the occurrence of outcomes or the end of the study. The associations between circulating choline levels and disease severity and prognoses were explored. RESULTS: Totally, 272 inpatients with PH were enrolled in this study. Patients were divided into high and low choline groups according to the 50th quartile of circulating choline levels, defined as 12.6 µM. After confounders adjustment, the high circulating choline levels were still associated with poor World Health Organization functional class, elevated N-terminal pro-B-type natriuretic peptide, and decreased cardiac output index indicating the severe disease condition. Moreover, elevated choline levels were associated with poor prognoses in PH patients even after adjusting for confounders (hazard ratio = 1.934; 95% CI, 1.034-3.619; P = 0.039). Subgroup analyses showed that choline levels predicted the prognosis of patients with pulmonary arterial hypertension but not chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Choline levels were associated with disease severity and poor prognoses of patients with PH, especially in pulmonary arterial hypertension suggesting its potential biomarker role.

The potential of cystatin C as a predictive biomarker in pulmonary hypertension.

BACKGROUND: Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. OBJECTIVE: The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). METHOD: We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. RESULTS: A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P < 0.001), mixed venous oxygen saturation (r = -0.216, P < 0.001), and tricuspid annular plane systolic excursion (r = -0.236, P < 0.001), and high cystatin C levels independently predicted a poor prognosis after adjusting potential confounders in different models (all P < 0.05). A three-group non-invasive risk model was constructed based on the combined assessment of the cystatin C and WHO-FC using dichotomous cut-off value. Those patients with higher cystatin C (≥ 1.0 mg/L) and a worse WHO-FC experienced the highest risk of endpoint occurrence. The predictive capacity of this model was comparable to that of an existing invasive risk stratification model (area under curve: 0.657 vs 0.643, P = 0.619). CONCLUSIONS: Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.

Hepatotoxicity evaluation and possible mechanisms of decabrominated diphenyl ethers (BDE-209) in broilers: Oxidative stress, inflammatory, and transcriptomics.

Decabrominated diphenyl ether (BDE-209), a persistent organic pollutant, is linked to a great number of health problems, the most severe of which impact the liver due to its role in the elimination and degradation of exogenous harmful substances. Though the hepatotoxicity of BDE-209 has been observed, its underlying mechanism is yet unknown. The purpose of this study is to thoroughly investigate the hepatotoxicity of BDE-209 and its molecular processes in broilers by subjecting 120 male broilers to varied concentrations of BDE-209 for 42 days. We observed that the bioaccumulation of BDE-209 in the liver in a dose-dependent manner, and that BDE-209 exposure can raise the concentrations of ALT, AST, and GGT, accompanied by hepatocyte fatty degeneration and inflammatory foci. In the hepatic homogenates, oxidative stress was evidenced by elevated levels of MDA and ROS and decreased activies of SOD and CAT. Additionally, pro-inflammatory cytokines including IL-1, IL-1ß, TNF-α, IL-8 levels were increased, whereas anti-inflammatory cytokine IL-4 level was declined. Furthermore, RNA sequencing revealed that genes involved in inflammation were considerably dysregulated, and real-time PCR verified the expressed alterations of numerous genes related to the MAPK and WNT signaling pathways. The protein concentrations of NF-κB, ß-catenin, and WNT5A, and the phosphorylation levels of JNK and ERK were all dramatically enhanced. The current study indicates that BDE-209 exposure can cause hepatotoxicity in broilers via bioaccumulation and oxidative stress, which then activates the MAPK and WNT signaling pathways, subsequently generating inflammation and hepatic injury.

Draft Genome Sequence Resource of Sweet Cherry Virescence Phytoplasma Strain SCV-TA2020 Associated with Sweet Cherry Virescence Disease in China.

Sweet cherry virescence phytoplasma strain SCV-TA2020, a related strain of 'Candidatus Phytoplasma ziziphi', is a pathogen associated with sweet cherry virescence disease in China. Here, we provide the first-draft genome sequence of SCV-TA2020, which consists of 775,344 bases, with a GC content of 23.21%. This will provide a reference for understanding the host selection and diversity of host-specific symptoms of 16SrV-B subgroup phytoplasmas.

Perceived social support and professional identity in nursing students during the COVID-19 pandemic era: the mediating effects of self-efficacy and the moderating role of anxiety.

BACKGROUND: Health professionals, including nurses, experienced heavy workloads and significant physical and mental health challenges during the coronavirus disease (COVID) 19 pandemic, which may affect career choices for those considering nursing and for nursing students. The COVID-19 pandemic is not only a period of risk, but also an occasion to redeploy the professional identity (PI) of nursing students. However, the relationship between perceived social support (PSS), self-efficacy (SE), PI and anxiety remains unclear under the background of COVID-19. This study aims to explore whether PSS has an indirect effect on PI through mediation of SE and whether the anxiety can moderate the relationship between PSS and SE in nursing students during their internship period. METHODS: An observational, national cross-sectional study was conducted following the STROBE guidelines. An online questionnaire was completed by 2,457 nursing students from 24 provinces in China during their internship during September to October 2021. Measures included Chinese translations of the Professional Identity Questionnaire for Nursing Students, the Perceived Social Support Scale, the General Self-Efficacy Scale, the 7-item Generalized Anxiety disorder scale. RESULTS: Both PSS (r = 0.46, p < 0.001) and SE (r = 0.51, p < 0.001) were positively correlated with PI. The indirect effect of PSS on PI through SE was positive (ß = 0.348, p < 0.001), with an effect of 72.7%. The results of the moderating effect analysis showed that anxiety attenuated the effect of PSS on SE. Moderation models indicated that anxiety has a weak negative moderating effect on the effect of PSS on SE (ß =-0.0308, p < 0.05). CONCLUSIONS: A better PSS and higher scores in SE were associated with PI in nursing students, and a better PSS had an indirect effect on the PI of nursing students through SE. Anxiety played a negative moderating role in the relationship between PSS and SE.