Effect of Magnetic Field on Maskless Localized Electrodepositing Three-Dimensional Microstructure of Nano Nickel Crystals.

In the intricate process of maskless localized electrodeposition (MLED) for fabricating three-dimensional microstructures, specifically nickel micro-columns with an aspect ratio of 7:1, magnetic fields of defined strength were employed, oriented both parallel and anti-parallel to the electric field. The aim was to achieve nanocrystalline microstructures and elevated deposition rates. A detailed comparative analysis was conducted to examine the volumetric deposition rate, surface morphology, and grain size of the MLED nickel crystal 3D microstructures, both in the absence and presence of the two magnetic field directions, facilitated by a self-assembled experimental setup. The results indicate that the anti-parallel magnetic field significantly boosts the volumetric deposition rate to a notable 19,050.65 µm3/s and refines the grain size, achieving an average size of 24.82 nm. Conversely, the parallel magnetic field is found to enhance the surface morphology of the MLED nickel crystal 3D microstructure.

Exposure of benzo[a]pyrene induces HCC exosome-circular RNA to activate lung fibroblasts and trigger organotropic metastasis.

BACKGROUND: Benzo[a]pyrene (B[a]P), a carcinogen pollutant produced by combustion processes, is present in the western diet with grilled meats. Chronic exposure of B[a]P in hepatocellular carcinoma (HCC) cells promotes metastasis rather than primary proliferation, implying an unknown mechanism of B[a]P-induced malignancy. Given that exosomes carry bioactive molecules to distant sites, we investigated whether and how exosomes mediate cancer-stroma communications for a toxicologically associated microenvironment. METHOD: Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells (7404-100Bap Exo) at an environmental relevant dose (100 nmol/L). Lung pre-education animal model was prepared via injection of exosomes and cytokines. The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array. HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis. Profile of B[a]P-exposed exosomes were determined by ceRNA microarray. Interactions between circular RNA (circRNA) and microRNAs (miRNAs) were detected using RNA pull-down in target lung fibroblasts. Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the "on-off" interaction of circRNA-miRNA pairs. We further developed an adeno-associated virus inhalation model to examine mRNA expression specific in lung, thereby exploring the mRNA targets of B[a]P induced circRNA-miRNA cascade. RESULTS: Lung fibroblasts exert activation phenotypes, including focal adhesion and motility were altered by 7404-100Bap Exo. In the exosome-educated in vivo model, fibrosis factors and pro-inflammatory molecules of are up-regulated when injected with exosomes. Compared to non-exposed 7404 cells, circ_0011496 was up-regulated following B[a]P treatment and was mainly packaged into 7404-100Bap Exo. Exosomal circ_0011496 were delivered and competitively bound to miR-486-5p in recipient fibroblasts. The down-regulation of miR-486-5p converted fibroblast to cancer-associated fibroblast via regulating the downstream of Twinfilin-1 (TWF1) and matrix metalloproteinase-9 (MMP9) cascade. Additionally, increased TWF1, specifically in exosomal circ_0011496 educated lungs, could promote cancer-stroma crosstalk via activating vascular endothelial growth factor (VEGF). These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion, as a consequence of a pre-metastatic niche formation. CONCLUSION: We demonstrated that B[a]P-induced tumor exosomes can deliver circ_0011496 to activate miR-486-5p/TWF1/MMP9 cascade in the lung fibroblasts, generating a feedback loop that promoted HCC metastasis.

Benefits of 12-month peer support for diabetes self management sustained at 18 months.

AIMS: To evaluate sustainability of peer support (PS) benefits in diabetes management. METHODS: Supporting a Peer Leader program through Community Health Centers (CHCs) included trainings and consultations from baseline to 12 months. Evaluation at baseline, 12-month, and 18-month follow-up included primary outcome, HbA1c, and other outcomes of SBP, DBP, LDLc, PHQ-8, diabetes distress, and EQ-5D. RESULTS: 1284 participants with type 2 diabetes mellitus were recruited from 9 CHCs. Mean (SD) for age = 68.00 (7.55) years, 43.07 % male, mean (SD) for diabetes duration = 11.79 (7.34) years. Across 18-months, linear mixed model analyses controlling for confounders found the least square mean (SE) of HbA1c improved significantly from 7.62 % (0.06 %) to 7.53 % (0.06 %) for all, and from 9.25 % (0.09 %) to 8.52 % (0.11 %) among those ≥8 % at baseline. Parallel improvements were found among all for SBP, DBP, PHQ-8, diabetes distress, and, among those elevated at baseline for all outcomes. EQ-5D showed significant but modest increase from baseline to 18 months. No significant reversals between 12 and 18 months were found except for LDLc. Supporting robustness of findings, patterns were similar across age, diabetes duration, and gender. CONCLUSIONS: Relative to the fundamentally progressive nature of diabetes, it is striking that improvements associated with PS were generally sustained after program support ended.

Exercise-induced improvement of glycemic fluctuation and its relationship with fat and muscle distribution in type 2 diabetes.

AIMS: Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise-induced glycemic response. MATERIALS AND METHODS: Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). RESULTS: Combined exercise training decreased SD of sensor glucose (SDSG, exercise-pre vs exercise-post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI-quantified fat and muscle distribution, including visceral fat area (ß = -0.761, p = .001) and mid-thigh muscle area (ß = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. CONCLUSIONS: Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.

Associations of change in body fat percentage with baseline body composition and diabetes remission after bariatric surgery.

OBJECTIVE: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. METHODS: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 × (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. RESULTS: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. CONCLUSIONS: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.

Contributions of Hyperactive Mutations in Mpro from SARS-CoV-2 to Drug Resistance.

The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistance-conferring mutations impact inhibitor binding or enzyme activity. Nirmatrelvir, the most widely used inhibitor currently used to treat SARS-CoV-2 infections, targets the main protease (Mpro) preventing it from processing the viral polyprotein into active subunits. Our previous work systematically analyzed resistance mutations in Mpro that reduce binding to inhibitors; here, we investigate mutations that affect enzyme function. Hyperactive mutations that increase Mpro activity can contribute to drug resistance but have not been thoroughly studied. To explore how hyperactive mutations contribute to resistance, we comprehensively assessed how all possible individual mutations in Mpro affect enzyme function using a mutational scanning approach with a fluorescence resonance energy transfer (FRET)-based yeast readout. We identified hundreds of mutations that significantly increased the Mpro activity. Hyperactive mutations occurred both proximal and distal to the active site, consistent with protein stability and/or dynamics impacting activity. Hyperactive mutations were observed 3 times more than mutations which reduced apparent binding to nirmatrelvir in recent studies of laboratory-grown viruses selected for drug resistance. Hyperactive mutations were also about three times more prevalent than nirmatrelvir binding mutations in sequenced isolates from circulating SARS-CoV-2. Our findings indicate that hyperactive mutations are likely to contribute to the natural evolution of drug resistance in Mpro and provide a comprehensive list for future surveillance efforts.

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes.

Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Artificial intelligence for diabetes care: current and future prospects.

Artificial intelligence (AI) use in diabetes care is increasingly being explored to personalise care for people with diabetes and adapt treatments for complex presentations. However, the rapid advancement of AI also introduces challenges such as potential biases, ethical considerations, and implementation challenges in ensuring that its deployment is equitable. Ensuring inclusive and ethical developments of AI technology can empower both health-care providers and people with diabetes in managing the condition. In this Review, we explore and summarise the current and future prospects of AI across the diabetes care continuum, from enhancing screening and diagnosis to optimising treatment and predicting and managing complications.

DRAC 2022: A public benchmark for diabetic retinopathy analysis on ultra-wide optical coherence tomography angiography images.

We described a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). Within this challenge, we provided the DRAC datset, an ultra-wide optical coherence tomography angiography (UW-OCTA) dataset (1,103 images), addressing three primary clinical tasks: diabetic retinopathy (DR) lesion segmentation, image quality assessment, and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams submitting different solutions for these three tasks, respectively. This paper presents a concise summary and analysis of the top-performing solutions and results across all challenge tasks. These solutions could provide practical guidance for developing accurate classification and segmentation models for image quality assessment and DR diagnosis using UW-OCTA images, potentially improving the diagnostic capabilities of healthcare professionals. The dataset has been released to support the development of computer-aided diagnostic systems for DR evaluation.

Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota.

Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean -2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption. We demonstrate that RS can facilitate weight loss at least partially through B. adolescentis and that the gut microbiota is essential for the action of RS.

The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report

The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. Arch Endocrinol Metab. 2015;59(3):265-9.