A mutation-sensitive, multiplexed and amplification-free detection of nucleic acids by stretching single-molecule tandem hairpin probes.

The detection of nucleic acid sequences in parallel with the discrimination of single nucleotide variations (SNVs) is critical for research and clinical applications. A few limitations make the detection technically challenging, such as too small variation in probe-hybridization energy caused by SNVs, the non-specific amplification of false nucleic acid fragments and the few options of dyes limited by spectral overlaps. To circumvent these limitations, we developed a single-molecule nucleic acid detection assay without amplification or fluorescence termed THREF (hybridization-induced tandem DNA hairpin refolding failure) based on multiplexed magnetic tweezers. THREF can detect DNA and RNA sequences at femtomolar concentrations within 30 min, monitor multiple probes in parallel, quantify the expression level of miR-122 in patient tissues, discriminate SNVs including the hard-to-detect G-U or T-G wobble mutations and reuse the probes to save the cost. In our demonstrative detections using mock clinic samples, we profiled the let-7 family microRNAs in serum and genotyped SARS-CoV-2 strains in saliva. Overall, the THREF assay can discriminate SNVs with the advantages of high sensitivity, ultra-specificity, multiplexing, reusability, sample hands-free and robustness.

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

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

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

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

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

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

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

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

Association Between Myocardial Oxygenation and Fibrosis in Duchenne Muscular Dystrophy: Analysis by Rest Oxygenation-Sensitive Magnetic Resonance Imaging.

BACKGROUND: Myocardial hypoxia has been demonstrated in many cardiomyopathies and is related to development of myocardial fibrosis. However, myocardial hypoxia and its association with myocardial fibrosis are understudied in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy. PURPOSE: To evaluate myocardial hypoxia by oxygenation-sensitive (OS) cardiac magnetic resonance imaging, and further explore its association with fibrosis. STUDY TYPE: Prospective. SUBJECTS: Ninety-one DMD boys (8.78 ± 2.32) and 30 healthy boys (9.07 ± 2.30). FIELD STRENGTH/SEQUENCE: 3 T, Balanced steady-state free procession, Modified Look-Locker inversion recovery sequence and Single-shot phase-sensitive inversion recovery sequence. ASSESSMENT: Cardiac MRI data, including left ventricular functional, segmental native T1, and oxygenation signal-intensity (SI) according to AHA 17-segment model, were acquired. Patients were divided into LGE+ and LGE- groups. In patients with LGE, all segments were further classified as positive or negative segments by segmentally presence/absence of LGE. STATISTICAL TESTS: Variables were compared using Student's t, Wilcoxon, Kruskal-Wallis test and one-way analysis of variance. Bivariate Pearson or Spearman correlation were calculated to determine association between oxygenation SI and native T1. Variables with P < 0.10 in the univariable analysis were included in multivariable model. Receiver operating characteristic analysis was used to assess the performance of OS in diagnosing myocardial hypoxia. RESULTS: The myocardial oxygenation SI of DMD was significantly decreased in all segments compared with normal controls, and more obvious in the LGE+ segments (0.46 ± 0.03 vs. 0.52 ± 0.03). For patients with and without LGE, myocardial oxygenation SI were significantly negatively correlated with native T1 in all segments (r = -0.23 to -0.42). The inferolateral oxygenation SI was a significant independent associator of LGE presence (adjusted OR = 0.900). DATA CONCLUSION: Myocardial hypoxia evaluated by the OS-Cardiac-MRI indeed occurs in DMD and associate with myocardial fibrosis, which might be used as a biomarker in assessing myocardial damage in DMD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Life-Cycle Environmental Impacts of Additive-Related Chemicals in Polyvinyl Chloride Plastics and the Mitigation Potential.

Plastic additive-related chemicals, particularly in polyvinyl chloride (PVC) plastics, have become a key issue in plastic pollution. Although addressing plastic pollution through the life-cycle approach is crucial, the environmental impacts of typical plastic additive-related chemicals in PVC plastics during the cradle-to-gate stage remain unexplored. Consequently, managing the life-cycle environmental impacts of these additives remains challenging. Herein, the environmental impacts of 23 typical plastic additive-related chemicals and six PVC plastic products were evaluated throughout the cradle-to-gate life-cycle stage using a life cycle assessment-material flow analysis (LCA-MFA) coupled model. The results indicate that plastic additives significantly contribute to the environmental impacts of PVC plastic products across various end point indicators, ranging from 8.7 to 40.6%. Additionally, scenario analysis (SA) reveals that conventional strategies for addressing plastic pollution may not be highly effective in mitigating the environmental impacts associated with plastic additives. Specifically, compared to primary polymers, these additives exhibit 4 to 13% lower mitigation potential under the same policy scenarios. However, technical adjustment strategies targeting additives show a mitigation potential of 12 to 39%, suggesting that guiding the plastic additive industry toward green transformation is a key strategy for reducing environmental impacts.

Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance.

BACKGROUND: Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors. METHOD: CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors. RESULTS: Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1-2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (ß = -0.425, P = 0.019) and LVRI (ß = -0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (ß = 0.429, P = 0.022). In the CKD stage 3-5 group, higher in systolic blood pressure (SBP) (ß = 0.464, P = 0.005) and PCR (ß = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3-5 group with hypertension than those without. CONCLUSION: Cardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3-5. Strict BP control may help reverse or prevent remodeling.

The influence of resourcefulness on the family functioning of young- and middle-aged lymphoma patients in China: a cross-sectional study.

BACKGROUND: Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. OBJECTIVE: This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. METHODS: A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. RESULTS: The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (ß = 0.338, 95% CI (0.072, 0.173)), spouse caregiver (ß = 0.376, 95% CI (1.938, 10.395)), and cancer stage (ß = -0.274, 95% CI (-3.219, -1.047)). Resourcefulness (ß = 0.438, 95% CI (0.096, 0.181)), spouse caregiver (ß = 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (ß = 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. CONCLUSIONS: Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them.

Identification of flexible Pif1-DNA interactions and their impacts on enzymatic activities.

Flexible regions in biomolecular complexes, although crucial to understanding structure-function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structure determination methods. Taking two Pif1 helicases (ScPif1 and BsPif1) as model systems, we found that, besides a few tightly bound nucleotides, adjacent solvent-exposed nucleotides interact dynamically with the helicase surfaces. The whole nucleotide segment possessed curved conformations and covered the two RecA-like domains of the helicases, which are essential for the inch-worm mechanism. The synergetic approach reveals that the interactions between the exposed nucleotides and the helicases could be reduced by large stretching forces or electrostatically shielded with high-concentration salt, subsequently resulting in reduced translocation rates of the helicases. The dynamic interactions between the exposed nucleotides and the helicases underlay the force- and salt-dependences of their enzymatic activities. The present single-molecule based approach complements high-resolution structural methods in deciphering the molecular mechanisms of the helicases.

"Access to pharmacy services is difficult in China": a qualitative study from the perspective of transplant recipients to explore their expectations.

PURPOSE: To gain an in-depth and comprehensive understanding of Chinese organ transplant recipients' perceptions, expectations, and suggestions of pharmacy services to hospital pharmacists. METHODS: This qualitative study was conducted in central China, from February to December 2020. Participants were collected with a purposive and snowball sampling method. Focus group discussions were conducted with organ transplant recipients and content analysis was applied to identify themes and subthemes. RESULTS: 21 recipients participated in the qualitative study. Four themes and thirteen subthemes were identified: (1) perceptions of clinical pharmacists and pharmacy services; (2) expectations for pharmacy service content; (3) expectations for pharmacy service form; and (4) difficulties as a special group. CONCLUSION: The pharmacy services provided by Chinese healthcare institutions are inadequate to meet the needs of organ transplant recipients. However, the acceptance and expectation of pharmacy services by transplant recipients are high. Therefore, China should learn from the experience of developed countries and focus on the actual needs of patients to establish a better pharmacy service system for organ transplantation.

Chrysomycin A Reshapes Metabolism and Increases Oxidative Stress to Hinder Glioblastoma Progression.

Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.

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

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

Association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease with comorbidity: evidence in 17 cities of Henan, Central China.

Particulate matter (PM10) changes have been confirmed as one of the contributory factors affecting human health, the association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease (COPD) with comorbidity diseases was rarely reported. The same inpatient more than twice times admissions with COPD illness from January 1, 2016 to December 31, 2021 were identified from hospitals in the 17 cities of Henan, Central China. City-specific associations were firstly estimated using the case time series (CTS) model and then combined to obtain the regional average association. The multivariate meta-analytic model produces pooled estimates of the set of coefficients representing the PM10-COPD hospitalizations association across the 17 cities. Cause-specific hospitalization analyses were performed by COPD patients with different comorbidity combinations. A total of 34,348 elderly (age ≥ 65) subjects were analyzed and with a total of 35,122.35 person-years. These coefficients can be used to compute the linear exposure-response curve expressed as relative risk (RR) in per 10 µg/m3 increase in PM10 at lag03, which was 1.0091 (95% CI 1.0070-1.0112) for COPD with comorbidity, 1.0089 (95% CI 1.0067-1.0110) for COPD with circulatory system diseases, 1.0079 (95% CI 1.0052-1.0105) for COPD with respiratory system diseases, 1.0076 (95% CI 1.0032-1.0121) for COPD with endocrine system diseases, and 1.0087 (95% CI 1.0013-1.0162) for COPD with genitourinary system diseases, respectively. Some heterogeneity was found across cities, with estimates ranging from 1.0227 in the Puyang and Jiaozuo to 1.0053 in Henan Provance, China. The effect of higher PM10, on average, was higher in studies for northern cities, with a steeper raise in risk: per 10 µg/m3 increase in PM10, the RR from 1.0062 (95% CI 1.0030-1.0093) for the 10th percentile of latitude to 1.0124 (95% CI 1.0089-1.0160) for the 90th percentile. Our findings indicated that PM10 exposure may increase the risk of hospitalizations for COPD with comorbidity. Moreover, there might be a higher morbidity risk associated with PM10 in northern latitudes, indicating that stricter air quality standards could potentially reduce PM10-related morbidity among individuals with COPD. These findings have implications for the implementation of effective clean air interventions aligned with national climate policies.

Isospongian Diterpenoids from the Leaves of Amomum tsao-ko Promote GLP-1 Secretion via Ca2+/CaMKII and PKA Pathways and Inhibit DPP-4 Enzyme.

Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7% and 186.1% (60 µM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca2+/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed moderate DPP-4 inhibitory activity with an IC50 value of 311.0 µM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity.

Comorbidity Patterns in Chronic Obstructive Pulmonary Disease and Their Associations with Service Utilization.

BACKGROUND: The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data. AIMS: To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission. METHODS: The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates. RESULTS: The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82-1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58-12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37-1.46). CONCLUSION: Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.

Highly Antibacterial and Antioxidative Carbon Nanodots/Silk Fibroin Films for Fruit Preservation.

The issues of fruit waste and safety resulting from rot have spurred a demand for improved packaging systems. Herein, we present highly antibacterial and antioxidative carbon nanodot/silk fibroin (CD/SF) films for fruit preservation. The films are composed of CDs and SF together with a small amount of glycerol via hydrogen bonding, exhibiting outstanding biosafety, transparency, and stretchability. The films effectively integrate key functionalities (atmosphere control, resistance to food-borne pathogens, and antioxidation properties) and can be manufactured in large sizes (about 20 × 30 cm), boasting a transmission rate of 13 183 cm3/m2·day for oxygen and 2860 g/m2·day for water vapor, favoring the preservation of fresh fruits. A convenient dip-coating method enables in situ fabrication of films with a thickness of approximately 14 µm directly on the fruits' surface providing comprehensive protection. Importantly, the films are washable and biodegradable. This work presents a promising technology to produce multifunctional and eco-friendly antibacterial packaging systems.

Associations between the polymorphisms of main components in PI3K/Akt pathway and risk of diabetic kidney disease: A meta-analysis.

AIMS: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta-analysis. METHODS: Case-control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4. RESULTS: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL-6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2  = 75%, OR = 1.29, 95%CI 1.07-1.56; MM + WM vs. WW: I2  = 75%, OR = 1.50, 95%CI 1.21-1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2  = 63%, OR = 1.43, 95%CI 1.22-1.68; MM + WM vs. WW: I2  = 50%, OR = 1.36, 95%CI 1.16-1.58; MM vs. WM + WW: I2  = 59%, OR = 2.20, 95%CI 1.41-3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I2  = 47%, OR = 1.35, 95%CI 1.15-1.59; MM + WM vs. WW: I2  = 45%, OR = 1.32, 95%CI 1.07-1.62; MM vs. WM + WW: I2  = 65%, OR = 2.29, 95%CI 1.39-3.77). The "M" allele of IL-6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I2  = 23%, OR = 1.49, 95%CI 1.21-1.84; MM + WM vs. WW: I2  = 1%, OR = 1.43, 95%CI 1.15-1.77; MM + WM vs. WW: I2  = 71%, OR = 2.77, 95%CI 1.09-7.06). CONCLUSIONS: This meta-analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL-6 rs1800796 were related to the increased risk of DKD.

Evaluation of coronary microvascular dysfunction and risk factors in children and youth with Turner syndrome by magnetic resonance myocardial perfusion imaging.

OBJECTIVE: Turner syndrome (TS) has an increased predisposition to ischaemic heart disease and the status of coronary microcirculation in TS is largely unknown. This study aims to evaluate myocardial microvascular function in TS using first-pass magnetic resonance perfusion imaging and determine significant risk factors contributing to microvascular dysfunction in the early stage. DESIGN: Perspective cohort study. PATIENTS: The study cohort consisted of 67 children and youth with TS and 32 age- and gender-matched controls. Measurements Clinical characteristics, left ventricle (LV) volume and function and cardiovascular magnetic resonance-derived myocardial perfusion parameters were assessed. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for microvascular dysfunction. RESULT: Microvascular perfusion decreased in TS in global and segmented myocardium as reflected in the lower upslopecor and maximum signal intensity (MaxSI) of LV myocardium compared to controls. Multivariable linear regression analysis indicated that age (ß = -0.107, 95% confidence interval [CI] = -0.201 to -0.013, p = .026) and being overweight/obese (ß = -1.155, CI = -2.134 to -0.176, p = .021) were independent impact factors of microvascular dysfunction. Subgroup analysis showed the upslopecor of older patients with TS decreased more significantly compared with that of normal controls. Upslopecor and MaxSI were lower in overweight/obese patients with TS than in patients with normal body mass index (BMI) and controls. CONCLUSION: Myocardial microvascular dysfunction can occur in children and youth patients with TS. Age and overweight/obesity were the independent risk factors of microvascular dysfunction, which imply the importance of lowering BMI for the prevention of coronary heart disease in young TS population.

Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI.

BACKGROUND: Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity. METHODS: A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model. RESULTS: T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6-43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45-6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08-4.59; P = 0.030) in the diabetes cohort. CONCLUSIONS: Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.