Upregulation of circGDI2 inhibits tumorigenesis by stabilizing the expression of RNA m6A demethylase FTO in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is a malignant tumour that is difficult to identify and prone to metastasis and invasion. Circular RNAs (circRNAs) are important cancer regulators and can be used as potential biomarkers. However, OSCC-related circRNAs need to be further explored. We investigated the role of circGDI2 in OSCC and explored its downstream regulatory mechanisms. Methods: Quantitative real-time PCR was used to detect the expression levels of circGDI2 and fat mass and obesity-associated protein (FTO) in cells. Lentiviral transfection was used to construct stable circGDI2 overexpressing cells for subsequent cell function tests. RNA pull-down, RNA Immunoprecipitation (RIP), western blotting, and protein stability assays were conducted to detect circGDI2 binding proteins and their functions. CCK8, Transwell, and wound healing assays were used to verify cell functions after overexpressing circGDI2 or suppressing FTO expression. Animal experiments were performed to verify the results in vivo. Results: The expression of circGDI2 was markedly decreased in both OSCC cell lines and patient tissues. Overexpression of circGDI2 in OSCC cell lines led to decreased proliferation, migration, and invasion abilities. Knockdown of circGDI2 showed the opposite trend. CircGDI2 has been validated to interact with the FTO protein within cells, as evidenced by mass spectrometry and RIP assays. This interaction was found to prevent the degradation of the FTO protein. Dot blot analysis showed a reduction in N6-methyladenosine (m6A) modification after circGDI2 overexpression. Reduced FTO levels reversed the inhibitory effects of circGDI2 overexpression on cell proliferation, migration, and invasion in vitro and on tumorigenesis in vivo. Conclusions: CircGDI2 functions as a tumour suppressor by binding to the FTO protein to reduce RNA m6A modification levels and ultimately inhibit proliferation and migration in OSCC cells. This study indicates the potential use of circGDI2 as a new target for the prevention and treatment of OSCC.

Mendelian randomization reveals that abnormal lipid metabolism mediates the causal relationship between body mass index and keratoconus.

Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005-3.262, P = 0.048). Although IL-12ß and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention.

Establishment and assessment of an oral squamous cell carcinoma N7-methylguanosine methyltransferase associated microRNA prognostic model.

Background: N7-methylguanosine (m7G) methyltransferases and microRNAs (miRNAs) are closely associated with tumor progression. However, the role of m7G methyltransferase-related miRNAs as prognostic markers in oral squamous cell carcinoma (OSCC) has not been studied. This study aimed to explore the m7G methyltransferase-related miRNAs in OSCC, establish a prognostic model based on m7G methyltransferase-related miRNAs, investigate their correlation with immune cell infiltration, and assess their potential prognostic value. Methods: Transcriptional and clinical data of patients with OSCC were obtained from The Cancer Genome Atlas (TCGA) database. TargetScan and miRWalk were used to predict m7G methyltransferase-related miRNAs. Subsequently, differentially expressed m7G methyltransferase-related miRNAs in TCGA-OSCC were selected. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to build an m7G methyltransferase-related miRNA risk prognostic model for TCGA-OSCC. Patients were stratified into high- and low-risk groups. The predictive and diagnostic accuracies of the risk prognostic model were further validated using Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve analysis, independent prognosis analysis, and nomogram plots. Finally, quantitative real-time polymerase chain reaction (qPCR) was used to validate the expression levels of m7G methyltransferase-related miRNAs in postoperative cancer and adjacent normal tissues from 60 patients with OSCC. Results: Through Cox and LASSO regression analysis, six candidate miRNAs (hsa-miR-338-3p, hsa-miR-1251-3p, hsa-miR-3129-5p, hsa-miR-4633-3p, hsa-miR-216a-3p, and hsa-miR-6503-3p) most relevant to the prognosis of patients with OSCC were identified to construct an m7G methyltransferase-related miRNA risk prognostic model. In this model, the overall survival (OS) of the high-risk group was significantly shorter than that of the low-risk group (P < 0.001). The model effectively predicted prognosis and served as an independent prognostic indicator for patients with OSCC. Compared with the low-risk group, the high-risk group exhibited a significantly increased capacity for immune cell infiltration (P < 0.05), while the activation and initiation abilities of immune cells were decreased. Finally, six m7G methyltransferase-related miRNAs were validated in OSCC tissue samples. Conclusion: The risk prognostic model based on six m7G methyltransferase-related miRNAs can predict the OS rate of patients with OSCC and has the potential to guide individualized treatment. This prognostic model is closely associated with immune cell infiltration in patients with OSCC.

Characterization of sediment organic matter in the outer Yangtze River Estuary using stable isotopes, optical techniques, and FT-ICR-MS: Implications for the carbon burial mechanism.

The burial of sediment organic matter (SOM) in the estuary and shelf plays an important role in the global carbon cycle. However, it is challenging to determine the source, composition, and burial of SOM in the coastal sea, especially at the molecular level. This was explored in the coastal area outside the largest Yangtze River of China with multiple techniques including elemental and stable isotopic analysis, absorption spectroscopy, fluorescence excitation-emission matrices coupled with parallel factor analysis (EEMs-PARAFAC), and ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The end-member mixing analysis based on δ13C and δ15N showed a dominance of marine contribution (up to 70%) at most stations while the terrestrial contribution increased to >55% nearshore in summer at a high fluvial sediment flux. This was consistent with the offshore decreasing humic-like C1 and C2, humification index (HIX), %lignin-like compounds, and %CHO but increasing tryptophan-like C3, biological index (BIX), %protein-like compounds, and %CHOS from EEMs-PARAFAC and FT-ICR-MS analysis. The %clay correlated positively with SOM content, HIX, %lignin-like compounds, O/C, and modified aromaticity index (AImod) but correlated negatively with %C3, H/C, and the relative abundance of labile formulas (MLBL), while %silt showed contrasting correlations. These results indicated the fine clay sediments adsorbed more humified, aromatic, oxygenated, and terrestrial compounds that were probably more resistant to biodegradation and thus had a higher burial efficiency than those on the silty sediments. Principal component analysis based on SOM indices further revealed different characteristics of SOM in the nearshore, northern offshore, and southern offshore regions, which were probably dependent on the delivery by local current systems. Overall, these findings contributed to unraveling the source and molecular composition of SOM associated with different grain size sediments and local current delivery, which are fundamental for understanding the factors underlying carbon burial in the complex coastal environment.

Safety and Effectiveness Outcomes between Apixaban Versus Vitamin K Antagonists in Atrial Fibrillation Patients on Dialysis.

Background: Anticoagulant therapy for atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) undergoing dialysis poses significant challenges. This review aimed to furnish clinicians with the latest clinical outcomes associated with apixaban and vitamin K antagonists (VKAs) in managing AF patients on dialysis. Methods: Literature from the PubMed and Embase databases up to March 2024 underwent systematic scrutiny for inclusion. The results were narratively summarized. Results: Six studies were included in this review, comprising the AXADIA-AFNET 8 study, the RENAL-AF trial, and four observational studies. In a French nationwide observational study, patients initiated on apixaban demonstrated a diminished risk of thromboembolic events (hazard ratios [HR]: 0.49; 95% confidence interval [CI]: 0.20-0.78) compared to those on VKAs. A retrospective review with a 2-year follow-up, encompassing patients with AF and ESKD on hemodialysis, evidenced no statistical difference in the risk of symptomatic bleeding and stroke between the apixaban and warfarin groups. Two retrospective studies based on the United States Renal Data System (USRDS) database both indicated no statistical difference between apixaban and VKAs in the risk of thromboembolic events. One study reported that apixaban correlated with a reduced risk of major bleeding relative to warfarin (HR: 0.72, 95% CI: 0.59-0.87), while the other study suggested that apixaban was associated with a decreased risk of mortality compared to warfarin (HR: 0.85, 95% CI: 0.78-0.92). The AXADIA-AFNET 8 study found no differences between apixaban and VKAs in safety or effectiveness outcomes for AF patients on dialysis. The RENAL-AF trial, however, was deemed inadequate for drawing conclusions due to its small sample size. Conclusions: Currently, the published studies generally support that apixaban exhibits non-inferior safety and effectiveness outcomes compared to VKAs for AF patients on dialysis.

Ultrasound-assisted low-temperature extraction of polysaccharides from Lavandula angustifolia Mill.: optimization, structure characterization, and anti-inflammatory activity.

Lavandula angustifolia Mill. is a traditional Chinese medicinal herb with high economic and pharmacological value. In this study, we optimized the conditions for low-temperature ultrasound-assisted extraction of L. angustifolia Mill. polysaccharides using response surface methodology (RSM), and two homopolysaccharides LAPW1 (33.6 kDa) and LAPS1 (95.9 kDa) were obtained after isolation and purification by DEAE-650 M and Superdex™ 200 chromatography. The primary structure of LAPS1 was determined using "partial acid hydrolysis, methylation, two-dimensional (2D NMR) spectroscopy" as the core method. The results revealed that LAPS1 is a heteropolysaccharide whose main chain consists of [-1)-ß-Galp-(6→1)-α-Araf-(5→]3-1-α-Araf-(3→1)-α-Araf-(5→[1)-ß-Galp-(6→1)-α-Araf-(5→]3-1-α-Araf-(5→1)-α-Araf-(5→[-1)-ß-Galp-(6→1)-α-Araf-(5→]3. In vitro experiments revealed that LAPW1 and LAPS1 significantly reduced the production of the inflammatory cytokines Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF), as well as the expression of Nitric Oxide Synthase 2 (NOS2) and release of nitric oxide (.NO) free radical in the inflammatory model established by lipopolysaccharide (LPS) stimulated RAW264.7. Besides, the zebrafish inflammatory model, stimulated by CuSO4, was employed to assess the impact of polysaccharides on neutrophil migration, indicating a notable decrease in zebrafish neutrophils and confirming their potential anti-inflammatory activity. These results indicate that polysaccharides from L. angustifolia Mill. be used in the development of functional foods and pharmaceutical products.

I n situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases.

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process of tumor antigen generation and loading, antigen drainage to lymph nodes (LNs), antigen internalization by dendritic cells (DCs), DC maturation, and antigen cross-presentation to activate T-cells. However, tumor vaccines are often unable to satisfy all the steps, leading to the limitation of their application and efficacy. Herein, based on a smart nanogel system, an in situ nano-vaccine (CpG@Man-P/Tra/Gel) targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer. The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib (Tra) and nano-adjuvant CPG@Man-P, which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P. Benefiting from mannose (Man) modification, the nano-vaccines targeted to LNs, promoted the uptake of antigens by DCs, further inducing the maturation of DCs and activation of T cells. Moreover, CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo. Notably, combined with PD-1 blocking, the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

Association of mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes.

BACKGROUND: Ferritin, a key indicator of body iron levels, has been reported to associate with type 2 diabetes (T2DM) and the onset of Gestational diabetes mellitus (GDM). However, limited research explores the association between mid-pregnancy ferritin levels and the risk of postpartum abnormal glucose metabolism (AGM) in patients with GDM. METHODS: A retrospective cohort study was conducted in 1514 women with GDM recruited from January 2016 to January 2021, and 916 women were included. Demographic characteristics, medical history and family history, pregnancy complications were recorded. Multiple logistic regression models were performed to assess the association between mid-pregnancy ferritin levels and the risk of postpartum AGM. RESULTS: Following the postpartum oral glucose tolerance test, 307 (33.5%) exhibited AGM. The AGM group had higher mid-pregnancy serum ferritin levels [AGM vs NGT: 23 (11.7, 69) µg/L vs 17.80 (9.85, 40.7) µg/L, P < 0.001] and had a larger proportion of women with ferritin levels ≥30 µg/L (AGM vs NGT: 43.6% vs 31.4%, P < 0.001). Logistic regression analysis demonstrated that women with ferritin levels≥ 30 µg/L had a 1.566 times higher risk of developing postpartum AGM. CONCLUSIONS: These findings indicate that elevated mid-pregnancy ferritin levels are significantly and independently associated with increased postpartum AGM risk in women with previous GDM. Consequently, cautious consideration is necessary for prescribing iron supplements in prenatal care, particularly for non-anemic women with GDM at high risk of developing diabetes after delivery.

The bifunctional impact of polylactic acid microplastics on composting processes and soil-plant systems: Dynamics of microbial communities and ecological niche competition.

Although extensive research has been conducted on the environmental impact of microplastics (MPs), their effects on microorganisms during the composting process and on the compost-soil system remain unclear. Our research investigates the microbial response to polylactic acid microplastics (PLAMPs) during aerobic composting and examines how compost enriched with PLAMPs affects plants. Our findings reveal that PLAMPs play a dual role in the composting process, influencing microorganisms differently depending on the composting phase. PLAMPs reduce the relative abundance of sensitive bacterial ASVs, specifically those belonging to Limnochordaceae and Enterobacteriaceae, during composting, while increasing the relative abundance of ASVs belonging to Steroidobacteriaceae and Bacillaceae. The impact of PLAMPs on microbial community assembly and niche width was found to be phase-dependent. In the stabilization phase (S5), the presence of PLAMPs caused a shift in the core microbial network from bacterial dominance to fungal dominance, accompanied by heightened microbial antagonism. Additionally, these intricate microbial interactions can be transferred to the soil ecosystem. Our study indicates that composting, as a method of managing PLAMPs, is also influenced by PLAMPs. This influence is transferred to the soil through the use of compost, resulting in severe oxidative stress in plants. Our research is pivotal for devising future strategies for PLAMPs management and predicting the subsequent changes in compost quality and environmental equilibrium.

Sliding Ferroelectricity Induced Ultrafast Switchable Photovoltaic Response in ε-InSe Layers.

2D sliding ferroelectric semiconductors have greatly expanded the ferroelectrics family with the flexibility of bandgap and material properties, which hold great promise for ultrathin device applications that combine ferroelectrics with optoelectronics. Besides the induced different resistance states for non-volatile memories, the switchable ferroelectric polarizations can also modulate the photogenerated carriers for potentially ultrafast optoelectronic devices. Here, it is demonstrated that the room temperature sliding ferroelectricity can be used for ultrafast switchable photovoltaic response in ε-InSe layers. By first-principles calculations and experimental characterizations, it is revealed that the ferroelectricity with out-of-plane (OOP) polarization only exists in even layer ε-InSe. The ferroelectricity is also demonstrated in ε-InSe-based vertical devices, which exhibit high on-off ratios (≈104) and non-volatile storage capabilities. Moreover, the OOP ferroelectricity enables an ultrafast (≈3 ps) bulk photovoltaic response in the near-infrared band, rendering it a promising material for self-powered reconfigurable and ultrafast photodetector. This work reveals the essential role of ferroelectric polarization on the photogenerated carrier dynamics and paves the way for hybrid multifunctional ferroelectric and optoelectronic devices.

Metadata information and fundus image fusion neural network for hyperuricemia classification in diabetes.

OBJECTIVE: In diabetes mellitus patients, hyperuricemia may lead to the development of diabetic complications, including macrovascular and microvascular dysfunction. However, the level of blood uric acid in diabetic patients is obtained by sampling peripheral blood from the patient, which is an invasive procedure and not conducive to routine monitoring. Therefore, we developed deep learning algorithm to detect noninvasively hyperuricemia from retina photographs and metadata of patients with diabetes and evaluated performance in multiethnic populations and different subgroups. MATERIALS AND METHODS: To achieve the task of non-invasive detection of hyperuricemia in diabetic patients, given that blood uric acid metabolism is directly related to estimated glomerular filtration rate(eGFR), we first performed a regression task for eGFR value before the classification task for hyperuricemia and reintroduced the eGFR regression values into the baseline information. We trained 3 deep learning models: (1) metadata model adjusted for sex, age, body mass index, duration of diabetes, HbA1c, systolic blood pressure, diastolic blood pressure; (2) image model based on fundus photographs; (3)hybrid model combining image and metadata model. Data from the Shanghai General Hospital Diabetes Management Center (ShDMC) were used to develop (6091 participants with diabetes) and internally validated (using 5-fold cross-validation) the models. External testing was performed on an independent dataset (UK Biobank dataset) consisting of 9327 participants with diabetes. RESULTS: For the regression task of eGFR, in ShDMC dataset, the coefficient of determination (R2) was 0.684±0.07 (95 % CI) for image model, 0.501±0.04 for metadata model, and 0.727±0.002 for hybrid model. In external UK Biobank dataset, a coefficient of determination (R2) was 0.647±0.06 for image model, 0.627±0.03 for metadata model, and 0.697±0.07 for hybrid model. Our method was demonstrably superior to previous methods. For the classification of hyperuricemia, in ShDMC validation, the area, under the curve (AUC) was 0.86±0.013for image model, 0.86±0.013 for metadata model, and 0.92±0.026 for hybrid model. Estimates with UK biobank were 0.82±0.017 for image model, 0.79±0.024 for metadata model, and 0.89±0.032 for hybrid model. CONCLUSION: There is a potential deep learning algorithm using fundus photographs as a noninvasively screening adjunct for hyperuricemia among individuals with diabetes. Meanwhile, combining patient's metadata enables higher screening accuracy. After applying the visualization tool, it found that the deep learning network for the identification of hyperuricemia mainly focuses on the fundus optic disc region.

A Bayesian Tensor Decomposition Method for Joint Estimation of Channel and Interference Parameters.

Bayesian tensor decomposition has been widely applied in channel parameter estimations, particularly in cases with the presence of interference. However, the types of interference are not considered in Bayesian tensor decomposition, making it difficult to accurately estimate the interference parameters. In this paper, we present a robust tensor variational method using a CANDECOMP/PARAFAC (CP)-based additive interference model for multiple input-multiple output (MIMO) with orthogonal frequency division multiplexing (OFDM) systems. A more realistic interference model compared to traditional colored noise is considered in terms of co-channel interference (CCI) and front-end interference (FEI). In contrast to conventional algorithms that filter out interference, the proposed method jointly estimates the channel and interference parameters in the time-frequency domain. Simulation results validate the correctness of the proposed method by the evidence lower bound (ELBO) and reveal the fact that the proposed method outperforms traditional information-theoretic methods, tensor decomposition models, and robust model based on CP (RCP) in terms of estimation accuracy. Further, the interference parameter estimation technique has profound implications for anti-interference applications and dynamic spectrum allocation.

Decreased complexity of glucose time series index associated with adverse pregnancy outcomes in gestational diabetes mellitus.

AIM: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis. RESULTS: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05). CONCLUSION: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM.

Effects of biochar and magnesium oxide on cadmium immobilized by microbially induced carbonate: Mobilization or immobilization in alkaline agricultural soils?

Microbially induced carbonate precipitation (MICP) is a promising technique for remediating heavy metal-contaminated soils. However, the effectiveness of MICP in immobilizing Cd in alkaline calcareous soils, especially when applied in agricultural soils, remains unclear. Biochar and magnesium oxide are two environmentally friendly passivating materials, and there are few reports on the combined application of MICP with passivating materials for remediating heavy metal-contaminated soils. Additionally, the number of treatments with MICP cement and the concentration of calcium chloride during the MICP process can both affect the effectiveness of heavy metal immobilization by MICP. Therefore, we conducted MICP and MICP-biochar-magnesium oxide treatments on agricultural soils collected from Baiyin, Gansu Province (pH = 8.62), and analyzed the effects of the number of treatments with cement and the concentration of calcium chloride on the immobilization of Cd by MICP and combined treatments. The results showed that early-stage MICP could immobilize exchangeable cadmium and increase the residual cadmium content, especially with high-concentration calcium chloride MICP treatment. However, in the later stage, soil nitrification and exchange processes led to the dissolution of carbonate-bound cadmium and cadmium activation. The fixing effect of MICP influence whether the MICP-MgO-biochar is superior to the MgO-biochar. Four treatments with cement were more effective than single treatment in MICP-biochar-magnesium oxide treatment, and the MICP-biochar-magnesium oxide treatment with four treatments was the most effective, with passivation rates of 40.7% and 46.6% for exchangeable cadmium and bioavailable cadmium, respectively. However, attention should be paid to the increase in soil salinity. The main mechanism of MICP-magnesium oxide-biochar treatment in immobilizing cadmium was the formation of Cd(OH)2, followed by the formation of cadmium carbonate.

Analysis and comparison of blood metabolome of forest musk deer in musk secretion and non-secretion periods.

Musk is an important animal product, but the musk secretion mechanism of forest musk deer (Moschus berezovskii) is still unclear. The musk synthesis process in forest musk deer is extremely complex, and many raw materials are directly or indirectly derived from forest musk deer blood. In this study, metabolomics was used to analyze the blood of forest musk deer in secretory and non-secretory phases for the first time, aim at explaining the secretion mechanism from the perspective of blood metabolism. We found that P450-related, choline-related, axonal regeneration and other pathways and related metabolites were significantly enriched during the musk secretion of forest musk deer. These pathways and metabolites related to P450 and choline in blood may have important implications for the mechanism of musk secretion in forest musk deer, because blood components were closely related to musk components and could provide raw materials for musk synthesis in musk gland cells.

The impact of lipoprotein(a) level on cardiac pathologies in diabetes: a cardiac CT study.

OBJECTIVES: We aimed to explore the imaging profile of coronary atherosclerosis, perivascular inflammation, myocardial perfusion, and interstitial fibrosis in diabetes stratified by lipoprotein(a) [Lp(a)] levels. METHODS: In this prospective study, we enrolled diabetic patients who had undergone computed tomography (CT) angiography, stress CT-myocardial perfusion imaging, and late iodine enhancement in 20 months. Then, we categorized them into elevated and normal groups based on an Lp(a) cutoff level of 30 mg/dL. All imaging data, including coronary atherosclerosis parameters, pericoronary adipose tissue (PCAT) density, stress myocardial blood flow (MBF), and extracellular volume (ECV), were collected for further analysis. RESULTS: In total, 207 participants (mean age: 59.1 ± 12.0 years, 111 males) were included in this study. Patients with elevated Lp(a) level had more pronounced percent atheroma volume (2.55% (1.01-9.01%) versus 1.30% (0-4.95%), p = 0.010), and demonstrated a higher incidence of positive remodeling, spotty calcification, and high-risk plaque (HRP) than those with normal Lp(a) levels (75.6% versus 54.8%, p = 0.015; 26.8% versus 9.6%, p = 0.003; 51.2% versus 30.1%, p = 0.011, respectively). Results of the multivariate analysis revealed that after adjusting for all clinical characteristics, elevated Lp(a) levels were an independent parameter associated with HRP (odds ratio = 2.608; 95% confidence interval: 1.254-5.423, p = 0.010). However, no significant difference was found between the two groups in terms of PCAT density, stress MBF, and ECV. CONCLUSIONS: Elevated Lp(a) levels are associated with extensive coronary atherosclerosis and HRP development. However, they are not related to perivascular inflammation, decreased myocardial perfusion, and interstitial fibrosis in diabetes. CLINICAL RELEVANCE STATEMENT: Elevated lipoprotein(a) levels are associated with extensive coronary atherosclerosis and a high incidence of HRPs. However, they are not related to perivascular inflammation, decreased myocardial perfusion, and interstitial fibrosis in diabetes. KEY POINTS: Diabetes is a known risk factor that accelerates cardiovascular disease progression. Diabetics with elevated lipoprotein(a) (Lp(a)) levels had a higher percent atheroma volume and positive remodeling, spotty calcification, and HRPs. Patients with diabetes should be screened for elevated Lp(a) using CCTA for comprehensive evaluation of atherosclerotic characteristics.

Machine Learning-Based Prediction of Large-for-Gestational Age Infants in Mothers with Gestational Diabetes Mellitus.

CONTEXT: Large-for-gestational-age (LGA), one of the most common complications of gestational diabetes mellitus (GDM), has become a global concern. The predictive performance of common continuous glucose monitoring (CGM) metrics for LGA is limited. OBJECTIVE: We aimed to develop and validate an artificial intelligence (AI) based model to determine the probability of women with GDM giving birth to LGA infants during pregnancy using CGM measurements together with demographic data and metabolic indicators. METHODS: A total of 371 women with GDM from a prospective cohort at a university hospital were included. CGM was performed during 20-34 gestational weeks, and glycemic fluctuations were evaluated and visualized in women with GDM who gave birth to LGA and non-LGA infants. A convolutional neural network (CNN)-based fusion model was developed to predict LGA. Comparisons among the novel fusion model and three conventional models were made using the area under the receiver-operating characteristic curve (AUCROC) and accuracy. RESULTS: Overall, 76 (20.5%) out of 371 GDM women developed LGA neonates. The visualized 24-h glucose profiles differed at midmorning. This difference was consistent among subgroups categorized by pregestational BMI, therapeutic protocol and CGM administration period. The AI based fusion prediction model using 24-h CGM data and 15 clinical variables for LGA prediction (AUCROC 0.852, 95% CI 0.680-0.966, accuracy 84.4%) showed superior discriminative power compared with the three classic models. CONCLUSIONS: We demonstrated better performance in predicting LGA infants among women with GDM using the AI based fusion model. The characteristics of the CGM profiles allowed us to determine the appropriate window for intervention.

Effectiveness of Psychobiotic Bifidobacterium breve BB05 in Managing Psychosomatic Diarrhea in College Students by Regulating Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled Trial.

Diarrhea of college students (DCS) is a prevalent issue among college students, affecting their daily lives and academic performance. This study aims to explore the potential effect of Bifidobacterium breve BB05 supplements on the DCS. Initially, fifty healthy and fifty diarrheal students were recruited in the observational experiment and allocated into control and diarrhea groups, respectively. Subsequently, one hundred diarrheal students were newly recruited in the intervention experiment and randomly allocated into placebo and probiotic groups, both treated for 2 weeks. Questionnaires (BSS, HAMA-14, and HDRS-17) were performed to assess the students' diarrheal states and mental health at baseline and post-treatment. Fecal samples underwent 16S rRNA sequencing and Enzyme-Linked Immunosorbent Assay to evaluate gut microbiota and fecal metabolite alternations. Results indicated that B. breve BB05 supplementation significantly enriched (p < 0.05) the reduced gut microbial diversity caused by diarrhea. Diarrhea resulted in notable alterations in gut microbiota composition, as exhibited by elevated Collinsella and Streptococcus, alongside substantially decreased Bifidobacterium, Bacteroides, and Prevotella, while B. breve BB05 supplementation partially restored the compromised gut microbiota at both the phylum and genus levels, particularly by increasing Bifidobacterium and Roseburia (p < 0.05). Importantly, questionnaire results suggested that B. breve BB05 administration achieved superior efficacy in relieving diarrhea symptoms and the associated anxiety and depression in college students. An increased fecal concentration of 5-hydroxytryptamine (5-HT) was also observed in the probiotic group, while Acetylcholine (ACH), Epinephrine (EPI), and Noradrenaline/Norepinephrine (NANE) reduced, revealing the potential of B. breve BB05 in alleviating anxiety and depression via modulating the microbiota-gut-brain axis. Furthermore, correlation analysis suggested that the altered microbiota and fecal neurotransmitters were closely associated with the mental symptoms. These results endorse B. breve BB05 intervention as a promising and innovative approach to alleviate both diarrhea and mental health conditions among college students.