Impact of freeze-thaw cycles on the physicochemical properties and structure-function relationship of potato starch with varying granule sizes in frozen dough.

Starch, as a critical component of dough, significantly influences quality preservation during the freezing process. In particular, the fine structure of potato (B-type) starch in frozen processing is a subject of considerable interest. This study aims to investigate the intrinsic differences of B-type starch and the impact of freeze-thaw (F/T) treatment on its molecular structure and physicochemical properties. Chain length distribution and X-ray photoelectron spectroscopy were utilized to examine the structural characteristics of natural potato starch with different granule sizes. Furthermore, the fine structure, thermal properties, and rheological properties of the isolated starches after F/T treatment were analyzed. The results indicate that potato starch with smaller particle sizes exhibits higher surface CC and PO content along with a higher proportion of very short chains (DP < 6, 8.17 %) and long B chains (DP > 25, 20.68 %). The study found that after F/T treatment, the surface of small-sized starch granules was initially damaged, exhibiting threads on the surface centered on the umbilical point. Following F/T treatment, both the crystallinity (very large (VL): 24.52-18.36 %; small (S): 17.03-16.69 %) and short-range order (VL: 2.97-2.61; S: 2.71-2.35) of starch particle size decreased. Both the amylose content (20.88-14.57 %) and ΔH (10.15-8.62 J/g) of isolated starch after freeze-thaw-treated dough exhibited a decrease to varying degrees. With the exception of the fifth cycle, small-size starch particles exhibited relatively higher G' and G" values and showed significant changes as a result of F/T treatment, demonstrating high hardness and complex viscosity. Clarifying the physicochemical properties of potato starches with different granule sizes is expected to expand their applications in frozen dough.

Estimating global 0.1° scale gridded anthropogenic CO2 emissions using TROPOMI NO2 and a data-driven method.

Satellite remote sensing is a promising approach for monitoring global CO2 emissions. However, existing satellite-based CO2 observations are too coarse to meet the requirements of fine-scale global mapping. We propose a novel data-driven method to estimate global anthropogenic CO2 emissions at a 0.1° scale, which integrates emissions inventories and satellite data while bypassing the inadequate accuracy of CO2 observations. Due to the co-emitted anthropogenic emissions of nitrogen oxides (NOx = NO + NO2) and CO2, high-resolution NO2 measurements from the TROPOspheric Monitoring Instrument (TROPOMI) are employed to map the global anthropogenic emissions at a global 0.1° scale. We construct the driving features from NO2 data and also incorporate gridded CO2/NOx emission ratios and NOx/NO2 conversion ratios as driving data to describe co-emissions. Both ratios are predicted using a long short-term memory (LSTM) neural network (with an R2 of 0.984 for the CO2/NOx emission ratio and an R2 of 0.980 for the NOx/NO2 conversion ratio). The data-driven model for estimating anthropogenic CO2 emissions is implemented by random forest regression (RFR) and trained using the Emissions Database for Global Atmospheric Research (EDGAR). The satellite-based anthropogenic CO2 emission dataset at a global 0.1° scale agrees well with the national CO2 emission inventories (an R2 of 0.998 with Global Carbon Budget (GCB) and an R2 of 0.996 with EDGAR) and consistent with city-level emission estimates from Carbon Monitor Cities (CMC) with the R2 of 0.824. This data-driven method based on satellite-observed NO2 provides a new perspective for fine-resolution anthropogenic CO2 emissions estimation.

Locoregional interventional therapy for hepatocellular carcinoma: radiologic and clinical factors predictive of untreatable progression and time to untreatable progression.

Objective: In this retrospective cohort study, independent risk factors that influence untreatable progression (UP) and time to UP (TTUP) in patients with hepatocellular carcinoma (HCC) after locoregional interventional therapy were examined. The effects of initial response and best response on UP occurrence and TTUP after locoregional interventional therapy were evaluated. Methods: Data were collected from HCC patients who were initially treated with the drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) procedure at our hospital from January 2017 to December 2022. Modified response evaluation criteria in solid tumors (m-RECIST) was used to evaluate the radiologic response of tumors. Logistic regression analysis was used to analyze the risk factors for UP in patients, and Cox regression analysis was used to discover independent variables that influenced TTUP. Results: A total of 93 patients who initially underwent the DEB-TACE procedure were included. Subsequent to initial treatment, 50 patients continued with DEB-TACE treatment, while 43 received DEB-TACE and sequential thermal ablation treatment. The probability of developing UP was 82.8% (n = 77). Furthermore, 49 (52.7%) patients achieved an initial response, and 70 (75.3%) achieved the best response. Multivariate logistic regression analysis confirmed three independent risk factors of UP, namely, age (odds ratio [OR]: 0.950, p = 0.044); initial response (OR: 0.177, p = 0.020); and treatment regimen (OR: 7.133, p = 0.007). Multivariate Cox regression found that total bilirubin (hazard ratio [HR]: 1.029, p = 0.002), tumor distribution (HR: 1.752, p = 0.034), Subjective Angiographic Chemoembolization Endpoint (SACE) classification (HR: 0.668, p = 0.043), number of tumors (HR: 1.130, p = 0.004), initial response (HR: 0.539, p = 0.019), and treatment regimen (HR: 4.615, p < 0.001) were independent variables that influenced TTUP. Conclusions: Age, initial response, and treatment regimen significantly affected the occurrence of UP in HCC patients. Initial response, SACE classification, treatment regimen, total bilirubin, number of tumors, and tumor distribution were significantly correlated with TTUP. The initial response following locoregional interventional therapy had greater effects on UP occurrence and TTUP than the best response.

Effect of low-dose terazosin on arterial stiffness improvement: A pilot study.

Arterial stiffness, a prominent hallmark of ageing arteries, is a predictor of all-cause mortality. Strategies for promoting healthy vascular ageing are encouraged. Here we conducted a pilot study to evaluate the potential effects of low-dose Terazosin on arterial stiffness. We enrolled patients aged over 40 with elevated arterial stiffness, defined as a brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, who were administered Terazosin (0.5 and 1.0 mg/day) from December 2020 to June 2023. Treatment responses were assessed every 3 months. Linear regression analysis was used to characterise the improvement. We matched cases who took Terazosin for 1 year with Terazosin-free controls using propensity score matching (PSM). Our findings demonstrate that Terazosin administration significantly affected arterial stiffness. (1) Arterial stiffness significantly improved (at least a 5% reduction in baPWV) in 50.0% of patients at 3 months, 48.6% at 6 months, 59.3% at 9 months, and 54.4% at 12 months, respectively. (2) Those with higher baseline baPWV and hypertension exhibited a significantly reduced risk of non-response. (3) Terazosin was associated with a reduction of baPWV at 1-year follow-up (linear regression: ß = -165.16, p < 0.001). This pilot study offers valuable insights into the potential significance of Terazosin in improving arterial stiffness and paves the way for future randomised clinical trials in combating vascular ageing.

A position-enhanced sequential feature encoding model for lung infections and lymphoma classification on CT images.

PURPOSE: Differentiating pulmonary lymphoma from lung infections using CT images is challenging. Existing deep neural network-based lung CT classification models rely on 2D slices, lacking comprehensive information and requiring manual selection. 3D models that involve chunking compromise image information and struggle with parameter reduction, limiting performance. These limitations must be addressed to improve accuracy and practicality. METHODS: We propose a transformer sequential feature encoding structure to integrate multi-level information from complete CT images, inspired by the clinical practice of using a sequence of cross-sectional slices for diagnosis. We incorporate position encoding and cross-level long-range information fusion modules into the feature extraction CNN network for cross-sectional slices, ensuring high-precision feature extraction. RESULTS: We conducted comprehensive experiments on a dataset of 124 patients, with respective sizes of 64, 20 and 40 for training, validation and testing. The results of ablation experiments and comparative experiments demonstrated the effectiveness of our approach. Our method outperforms existing state-of-the-art methods in the 3D CT image classification problem of distinguishing between lung infections and pulmonary lymphoma, achieving an accuracy of 0.875, AUC of 0.953 and F1 score of 0.889. CONCLUSION: The experiments verified that our proposed position-enhanced transformer-based sequential feature encoding model is capable of effectively performing high-precision feature extraction and contextual feature fusion in the lungs. It enhances the ability of a standalone CNN network or transformer to extract features, thereby improving the classification performance. The source code is accessible at https://github.com/imchuyu/PTSFE .

Case report: Regression after low-dose glucocorticoid therapy in a case of acute immune myocarditis induced by anti-PD-1 therapy for NSCLC.

Background: PD-1 inhibitors exhibit efficacy in managing unresectable/metastatic driver gene-negative NSCLC, albeit with potential immune-related adverse events (irAEs). Among these, immune checkpoint inhibitor-associated myocarditis (ICI-M) is rare yet lethal. This study presents the initial successful instance of ICI-M in a lung cancer patient, rescued by low-dose glucocorticoids post-deterioration during treatment. Case summary: A 78-year-old male with a medical history of stage IV pT3N2M1 NSCLC underwent four cycles of palliative chemotherapy, resulting in stable disease (SD). Subsequent to declining further chemotherapy, the patient was transitioned to a targeted therapy regimen comprising Anlotinib in conjunction with PD-1 inhibitor immunotherapy. On the 26th day post-administration of the PD-1 inhibitor, the patient manifested Grade 2 immune-mediated myocarditis. Treatment encompassing 1mg/kg methylprednisolone combined with immunoglobulin shock therapy was initiated for 3 days, achieving symptomatic control. Nonetheless, upon tapering methylprednisolone dosage to 4-8mg/3-4d, the condition deteriorated, necessitating transfer to the intensive care unit. Methylprednisolone dosage was escalated to 80mg/day for 3 days, followed by gradual reduction by one-third to two-thirds weekly, culminating in the patient's safe discharge from the hospital. Conclusion: Immune-related myocarditis linked to checkpoint inhibitors is often managed effectively with high-dose glucocorticoid therapy. However, in Asian populations, low-dose glucocorticoids are increasingly utilized for salvage therapy, yielding favorable outcomes and improving prognosis compared to European populations.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Macrophage-Derived GSDMD Plays an Essential Role in Atherosclerosis and Cross Talk Between Macrophages via the Mitochondria-STING-IRF3/NF-κB Axis.

BACKGROUND: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release. METHODS: ApoE-/- and Gsdmd-/- ApoE-/- mice, bone marrow transplantation, and AAV (adeno-associated virus serotype 9)-F4/80-shGSDMD (shRNA-GSDMD) were used to examine the effect of macrophage-derived GSDMD on atherosclerosis. Single-cell RNA sequencing was used to investigate the changing profile of different cellular components and the cellular localization of GSDMD during atherosclerosis. RESULTS: First, we found that GSDMD is activated in human and mouse atherosclerotic plaques and Gsdmd-/- attenuates the atherosclerotic lesion area in high-fat diet-fed ApoE-/- mice. We performed single-cell RNA sequencing of ApoE-/- and Gsdmd-/- ApoE-/- mouse aortas and showed that GSDMD is principally expressed in atherosclerotic macrophages. Using bone marrow transplantation and AAV-F4/80-shGSDMD, we identified the potential role of macrophage-derived GSDMD in aortic pyroptosis and atherosclerotic injuries in vivo. Mechanistically, GSDMD contributes to mitochondrial perforation and mitochondrial DNA leakage and subsequently activates the STING (stimulator of interferon gene)-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) axis. Meanwhile, GSDMD regulates the STING pathway activation and macrophage migration via cytokine secretion. Inhibition of GSDMD with GSDMD-specific inhibitor GI-Y1 (GSDMD inhibitor Y1) can effectively alleviate the progression of atherosclerosis. CONCLUSIONS: Our study has provided a novel macrophage-derived GSDMD mechanism in the promotion of atherosclerosis and demonstrated that GSDMD can be a potential therapeutic target for atherosclerosis.

The association between pulse wave velocity and pregnancy-associated diseases: A systematic review and meta-analysis.

Background: Maintaining healthy vascular structure and function is important for a healthy pregnancy. Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between pulse wave velocity (PWV), a well-recognized parameter for arterial stiffness assessment, and pregnancy-associated diseases is still unclear. Therefore, we conducted this systematic review, and a meta-analysis was performed to assess the relevant associations. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles on PWV and pregnancy-associated diseases published before April 2023. The mean with standard deviation was used to assess the differences in PWV in pregnant women with or without relevant diseases. Subgroup analysis was conducted according to specific types of PWV. The Newcastle‒Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 6488 individuals from 21 studies were included. All enrolled studies were high-quality. Overall, the PWV was elevated in pregnant women who suffered from preeclampsia (mean difference (MD) = 0.67, 95 % confidence interval (CI): 0.51,0.83, P < 0.00001), hypertension (MD = 1.04, 95 % CI: 1.00,1.08, P < 0.00001), gestational diabetes mellitus (MD = 0.34, 95%CI: 0.19,0.48, P < 0.00001), and diabetes (MD = 0.49, 95%CI: 0.27,0.70, P < 0.00001). Subgroup analysis based on specific types of PWV showed similar results. Conclusion: In our study, PWV is elevated in pregnancy-associated diseases, including preeclampsia, hypertension, and diabetes. The PWV assessment should be regarded as a clinical routine for pregnant women to prevent and manage cardiovascular diseases during pregnancy.

The effect of obesity on the outcome of thoracic endovascular aortic repair: a systematic review and meta-analysis.

Background: Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between obesity and outcomes of thoracic endovascular aortic repair (TEVAR) is still unclear. This systematic review and meta-analysis was performed to assess the roles of obesity in the outcomes of TEVAR. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles regarding obesity and TEVAR that were published before July 2023. The odds ratio (OR) or hazard ratio (HR) was used to assess the effect of obesity on TEVAR outcomes. Body mass index (BMI) was also compared between patients experiencing adverse events after TEVAR and those not experiencing adverse events. The Newcastle-Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 7,849 patients from 10 studies were included. All enrolled studies were high-quality. Overall, the risk of overall mortality (OR = 1.49, 95% CI [1.02-2.17], p = 0.04) was increased in obese patients receiving TEVAR. However, the associations between obesity and overall complications (OR = 2.41, 95% CI [0.84-6.93], p = 0.10) and specific complications were all insignificant, including stroke (OR = 1.39, 95% CI [0.56-3.45], p = 0.48), spinal ischemia (OR = 0.97, 95% CI [0.64-1.47], p = 0.89), neurological complications (OR = 0.13, 95% CI [0.01-2.37], p = 0.17), endoleaks (OR = 1.02, 95% CI [0.46-2.29], p = 0.96), wound complications (OR = 0.91, 95% CI [0.28-2.96], p = 0.88), and renal failure (OR = 2.98, 95% CI [0.92-9.69], p = 0.07). In addition, the patients who suffered from postoperative overall complications (p < 0.001) and acute kidney injury (p = 0.006) were found to have a higher BMI. In conclusion, obesity is closely associated with higher risk of mortality after TEVAR. However, TEVAR may still be suitable for obese patients. Physicians should pay more attention to the perioperative management of obese patients.

Transurethral surgical treatment for benign prostatic hyperplasia with detrusor underactivity: a systematic review and meta-analysis.

BACKGROUND: The efficacy of surgical treatment for benign prostatic hyperplasia (BPH) patients with detrusor underactivity (DU) remains controversial. METHODS: To summarize relevant evidence, three databases (PubMed, Embase, and Web of Science) were searched from database inception to May 1, 2023. Transurethral surgical treatment modalities include transurethral prostatectomy (TURP), photoselective vaporization of the prostate (PVP), and transurethral incision of the prostate (TUIP). The efficacy of the transurethral surgical treatment was assessed according to maximal flow rate on uroflowmetry (Qmax), International Prostate Symptom Score (IPSS), postvoid residual (PVR), quality of life (QoL), voided volume, bladder contractility index (BCI) and maximal detrusor pressure at maximal flow rate (PdetQmax). Pooled mean differences (MDs) were used as summary statistics for comparison. The quality of enrolled studies was evaluated by using the Newcastle-Ottawa Scale. Sensitivity analysis and funnel plots were applied to assess possible biases. RESULTS: In this study, 10 studies with a total of 1142 patients enrolled. In BPH patients with DU, within half a year, significant improvements in Qmax (pooled MD, 4.79; 95% CI, 2.43-7.16; P < 0.05), IPSS(pooled MD, - 14.29; 95%CI, - 16.67-11.90; P < 0.05), QoL (pooled MD, - 1.57; 95% CI, - 2.37-0.78; P < 0.05), voided volume (pooled MD, 62.19; 95% CI, 17.91-106.48; P < 0.05), BCI (pooled MD, 23.59; 95% CI, 8.15-39.04; P < 0.05), and PdetQmax (pooled MD, 28.62; 95% CI, 6.72-50.52; P < 0.05) were observed after surgery. In addition, after more than 1 year, significant improvements were observed in Qmax (pooled MD, 6.75; 95%CI, 4.35-9.15; P < 0.05), IPSS(pooled MD, - 13.76; 95%CI, - 15.17-12.35; P < 0.05), PVR (pooled MD, - 179.78; 95%CI, - 185.12-174.44; P < 0.05), QoL (pooled MD, - 2.61; 95%CI, - 3.12-2.09; P < 0.05), and PdetQmax (pooled MD, 27.94; 95%CI, 11.70-44.19; P < 0.05). Compared with DU patients who did not receive surgery, DU patients who received surgery showed better improvement in PVR (pooled MD, 137.00; 95%CI, 6.90-267.10; P < 0.05) and PdetQmax (pooled MD, - 8.00; 95%CI, - 14.68-1.32; P < 0.05). CONCLUSIONS: Our meta-analysis results showed that transurethral surgery can improve the symptoms of BPH patients with DU. Surgery also showed advantages over pharmacological treatment for BPH patients with DU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023415188.

Network pharmacology and molecular docking analysis on Shenfu Qiangxin indicate mTOR is a potential target to treat heart failure.

BACKGROUND: Heart failure (HF) is one of the major causes of mortality worldwide with high recurrence rate and poor prognosis. Our study aimed to investigate potential mechanisms and drug targets of Shenfu Qiangxin (SFQX), a cardiotonic-diuretic traditional Chinese medicine, in treating HF. METHODS: An HF-related and SFQX-targeted gene set was established using disease-gene databases and the Traditional Chinese Medicine Systems Pharmacology database. We performed gene function and pathway enrichment analysis and constructed protein-protein interaction (PPI) network to investigate the potential mechanisms. We also performed molecular docking to analyze the interaction patterns between the active compounds and targeted protein. RESULTS: A gene set with 217 genes was identified. The gene function enrichment indicated that SFQX can regulate apoptotic process, inflammatory response, response to oxidative stress and cellular response to hypoxia. The pathway enrichment indicated that most genes were involved in PI3K-Akt pathway. Eighteen hub target genes were identified in PPI network and subnetworks. mTOR was the key gene among hub genes, which are involved in PI3K-Akt pathway. The molecular docking analysis indicated that 6 active compounds of SFQX can bind to the kinase domain of mTOR, which exerted potential therapeutic mechanisms of SFQX in treating HF. CONCLUSIONS: The results of network pharmacology analysis highlight the intervention on PI3K-Akt pathway of SFQX in the treatment of HF. mTOR is a key drug target to help protect myocardium.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases.

Background: Physical weakness and cardiovascular risk increase significantly with age, but the underlying biological mechanisms remain largely unknown. This study aims to reveal the causal effect of circulating metabolites on frailty, sarcopenia and vascular aging related traits and diseases through a two-sample Mendelian Randomization (MR) analysis. Methods: Exposures were 486 metabolites analyzed in a genome-wide association study (GWAS), while outcomes included frailty, sarcopenia, arterial stiffness, atherosclerosis, peripheral vascular disease (PAD) and aortic aneurysm. Primary causal estimates were calculated using the inverse-variance weighted (IVW) method. Methods including MR Egger, weighted median, Q-test, and leave-one-out analysis were used for the sensitive analysis. Results: A total of 125 suggestive causative associations between metabolites and outcomes were identified. Seven strong causal links were ultimately identified between six metabolites (kynurenine, pentadecanoate (15:0), 1-arachidonoylglycerophosphocholine, androsterone sulfate, glycine and mannose) and three diseases (sarcopenia, PAD and atherosclerosis). Besides, metabolic pathway analysis identified 13 significant metabolic pathways in 6 age-related diseases. Furthermore, the metabolite-gene interaction networks were constructed. Conclusion: Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.

Cohort profile for the Tongji Cardiovascular Health Study: a prospective multiomics cohort study.

PURPOSE: The Tongji Cardiovascular Health Study aimed to further explore the onset and progression mechanisms of cardiovascular disease (CVD) through a combination of traditional cohort studies and multiomics analysis, including genomics, metabolomics and metagenomics. STUDY DESIGN AND PARTICIPANTS: This study included participants aged 20-70 years old from the Geriatric Health Management Centre of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. After enrollment, each participant underwent a comprehensive series of traditional and novel cardiovascular risk factor assessments at baseline, including questionnaires, physical examinations, laboratory tests, cardiovascular health assessments and biological sample collection for subsequent multiomics analysis (whole genome sequencing, metabolomics study from blood samples and metagenomics study from stool samples). A biennial follow-up will be performed for 10 years to collect the information above and the outcome data. FINDINGS TO DATE: A total of 2601 participants were recruited in this study (73.4% men), with a mean age of 51.5±11.5 years. The most common risk factor is overweight or obesity (54.8%), followed by hypertension (39.7%), hyperlipidaemia (32.4%), current smoking (23.9%) and diabetes (12.3%). Overall, 13.1% and 48.7% of men and women, respectively, did not have any of the CVD risk factors (hypertension, hyperlipidaemia, diabetes, cigarette smoking and overweight or obesity). Additionally, multiomics analyses of a subsample of the participants (n=938) are currently ongoing. FUTURE PLANS: With the progress of the cohort follow-up work, it is expected to provide unique multidimensional and longitudinal data on cardiovascular health in China.

Associations between Erectile Dysfunction and Vascular Parameters: A Systematic Review and Meta-Analysis.

PURPOSE: Erectile dysfunction (ED) is associated with several vascular disorders, but the associations between ED and vascular parameters are still unclear. MATERIALS AND METHODS: We analyzed and synthesized a comprehensive range of studies from PubMed, Web of Science, and Scopus regarding the associations between ED and the following measures: ankle-brachial index (ABI), pulse wave velocity (PWV), intima-media thickness (IMT), nitrate-mediated dilation (NMD), flow-mediated dilation (FMD), augmentation index (AI), endothelial progenitor cells (EPCs) and other vascular parameters. Subgroup analysis was conducted according to specific types of parameters. Study quality was assessed by using the Newcastle-Ottawa Scale. Sensitivity analysis was conducted to confirm the robustness of the pooled results. RESULTS: Fifty-seven studies with 7,312 individuals were included. Twenty-eight studies were considered to be high-quality. ED patients had a 0.11 mm higher IMT (95% confidence interval [CI]: 0.07, 0.15), a 2.86% lower FMD (95% CI: -3.56, -2.17), a 2.34% lower NMD (95% CI: -3.37, -1.31), a 2.83% higher AI (95% CI: 0.02, 5.63), a 1.11 m/s higher PWV (95% CI: 0.01, 2.21), and a 0.72% lower percentage of EPCs (95% CI: -1.19, -0.24) compared to those without ED. However, ABI was similar between ED patients and non-ED individuals. According to sensitivity analysis, the pooled results were robust. CONCLUSIONS: Our study confirmed the associations between ED and several vascular parameters and highlighted the importance of prevention and management of vascular and endothelial dysfunction in ED patients.

Fibulin 1, targeted by microRNA-24-3p, promotes cell proliferation and migration in vascular smooth muscle cells, contributing to the development of atherosclerosis in APOE-/- mice.

Extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) are the main components of atherosclerosis (AS) plaque. VSMCs participate in plaque formation through phenotypic transformation. The complex interplay between ECM and VSMCs plays vital roles in the progression of AS throughout the disease. An in-depth investigation into the functions of ECM-related molecules in VSMC development might contribute to deciphering the complexity of AS pathogenesis. In this study, the roles and molecular mechanisms of the ECM-related molecule Fibulin-1 (FBLN1) in the development of AS and VSMCs were explored using RNA sequencing, bioinformatics analysis, and cell experiments. Furthermore, the expression of FBLN1, as determined by western blot analysis, immunohistochemistry, and real-time quantitative PCR, was significantly increased in AS vascular samples compared to normal vascular samples. Silencing the FBLN1 through AAV viral injection in mice revealed an improvement in AS. Functional analyses revealed that FBLN1 promoted VSMC proliferation, migration, and wound healing. Combined with RNA sequencing and TargetScan7.2 prediction data, 22 microRNAs (miRNAs) were found to have the potential for direct interaction with the FBLN1 3'UTR in VSMCs. Among these 22 miRNAs, it was demonstrated that microRNA-24-3p (miR-24-3p) could negatively regulate FBLN1 expression by directly binding to the FBLN1 3'UTR. Moreover, miR-24-3p inhibited cell proliferation, migration, and wound healing, and suppressed the expression of Ki67, matrix metalloproteinase-2 and -9 (MMP2/9) by targeting FBLN1 in VSMCs. Meanwhile, inhibition of FBLN1 expression could restrain VSMC phenotypic transformation. In conclusion, miR-24-3p inhibited VSMC proliferation and migration by targeting FBLN1. Additionally, multiple miRNAs with the potential to interact with the FBLN1 3'UTR were identified. These findings might deepen our understanding of ECM gene regulatory networks and the complex etiology of AS.

Resveratrol affects ccRCC cell senescence and macrophage polarization by regulating the stability of CCNB1 by RBM15.

Aim: The present study sought to investigate the therapeutic effect of resveratrol on clear cell renal cell carcinoma. Materials & methods: Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to verify the cell proliferation. Transwell, real-time quantitative transcription PCR, western blot and ß-galactosidase staining were used to verify the migration, macrophage polarization and senescence. The tumor inhibitory effect of resveratrol on clear cell renal cell carcinoma was verified in vivo. Results: This study confirmed that resveratrol could affect the stability of CCNB1 mRNA mediated by RBM15 and inhibit the cancer process by inhibiting the expression of EP300/CBP from the perspective of cell senescence. Conclusion: Resveratrol is able to treat clear cell renal cell carcinoma through RBM15-induced cell senescence.