Efficient photodegradation of perfluoroalkyl substances under visible light by hexagonal ZnIn2S4 nanosheets.

Perfluoroalkyl substances (PFASs) are typical persistent organic pollutants, and their removal is urgently required but challenging. Photocatalysis has shown potential in PFASs degradation due to the redox capabilities of photoinduced charge carriers in photocatalysts. Herein, hexagonal ZnIn2S4 (ZIS) nanosheets were synthesized by a one-pot oil bath method and were well characterized by a series of techniques. In the degradation of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), one kind of representative PFASs, the as-synthesized ZIS showed activity superior to P25 TiO2 under both simulated sunlight and visible-light irradiation. The good photocatalytic performance was attributed to the enhanced light absorption and facilitated charge separation. The pH conditions were found crucial in the photocatalytic process by influencing the OBS adsorption on the ZIS surface. Photogenerated e- and h+ were the main active species involved in OBS degradation in the ZIS system. This work confirmed the feasibility and could provide mechanistic insights into the degradation and defluorination of PFASs by visible-light photocatalysis.

Occult coronary microvascular dysfunction and ischaemic heart disease in patients with diabetes and heart failure.

BACKGROUND: Patients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF. METHODS: Prospectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). RESULTS: Final analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant. CONCLUSIONS: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.

Integrative genomics reveals the polygenic basis of seedlessness in grapevine.

Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a ∼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.

Limosilactobacillus fermentum HNU312 alleviates lipid accumulation and inflammation induced by a high-fat diet: improves lipid metabolism pathways and increases short-chain fatty acids in the gut microbiome.

A high-fat diet can cause health problems, such as hyperlipidemia, obesity, cardiovascular disease, and metabolic disorders. Dietary supplementation with beneficial microbes might reduce the detrimental effects of a high-fat diet by modulating the gut microbiome, metabolic pathways and metabolites. This study assessed the effects of Limosilactobacillus fermentum HNU312 (L. fermentum HNU312) on blood lipid levels, fat accumulation, inflammation and the gut microbiome in mice on a high-fat diet. The results indicate that L. fermentum HNU312 supplementation to high-fat diet-fed mice led to decreases of 7.52% in the final body weight, 22.30% in total triglyceride, 24.87% in total cholesterol, and 27.3% in low-density lipoprotein cholesterol. Furthermore, the addition of L. fermentum HNU312 significantly reduced the fat accumulation in the liver and adipose tissue by 18.99% and 32.55%, respectively, and decreased chronic inflammation induced by a high-fat diet. Further analysis of the gut microbiome revealed that on the one hand, L. fermentum HNU312 changed the structure of the intestinal microbiota, increased the abundance of beneficial intestinal bacteria related to lipid metabolism, and reversed the enrichment of lipid-related metabolic pathways. On the other hand, L. fermentum HNU312 increased the production of short-chain fatty acids, which can reduce liver inflammation and chronic inflammation induced by a high-fat diet. In summary, by regulating gut microbiota, L. fermentum HNU312 improved lipid metabolism pathways and increased short-chain fatty acids, which reduced body weight, blood lipids, fat accumulation and chronic inflammation caused by high-fat diets. Therefore, L. fermentum HNU312 could be a good candidate probiotic for ameliorating metabolic syndrome.

Lipid A-modified Escherichia coli can produce porcine parvovirus virus-like particles with high immunogenicity and minimal endotoxin activity.

BACKGROUND: A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body. RESULTS: In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group. CONCLUSION: Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits.

The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR.

BACKGROUND: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. OBJECTIVES: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. METHODS: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. RESULTS: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (-0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (-0.25 to 1.1; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [-0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03). CONCLUSIONS: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Convolutional neural network transformer (CNNT) for fluorescence microscopy image denoising with improved generalization and fast adaptation.

Deep neural networks can improve the quality of fluorescence microscopy images. Previous methods, based on Convolutional Neural Networks (CNNs), require time-consuming training of individual models for each experiment, impairing their applicability and generalization. In this study, we propose a novel imaging-transformer based model, Convolutional Neural Network Transformer (CNNT), that outperforms CNN based networks for image denoising. We train a general CNNT based backbone model from pairwise high-low Signal-to-Noise Ratio (SNR) image volumes, gathered from a single type of fluorescence microscope, an instant Structured Illumination Microscope. Fast adaptation to new microscopes is achieved by fine-tuning the backbone on only 5-10 image volume pairs per new experiment. Results show that the CNNT backbone and fine-tuning scheme significantly reduces training time and improves image quality, outperforming models trained using only CNNs such as 3D-RCAN and Noise2Fast. We show three examples of efficacy of this approach in wide-field, two-photon, and confocal fluorescence microscopy.

Stabilizing hexagonally close-packed phase in single-component block copolymers through rational symmetry breaking.

Despite being predicted to be a thermodynamically equilibrium structure, the absence of direct experimental evidence of hexagonally close-packed spherical phase in single-component block copolymers raises uncomfortable concerns regarding the existing fundamental phase principles. This work presents a robust approach to regulate the phase behavior of linear block copolymers by deliberately breaking molecular symmetry, and the hexagonally close-packed lattice is captured in a rigorous single-component system. A collection of discrete A1BA2 triblock copolymers is designed and prepared through an iterative growth method. The precise chemical composition and uniform chain length eliminates inherent size distribution and other molecular defects. Simply by tuning the relative chain length of two end A blocks, a rich array of ordered nanostructures, including Frank-Kasper A15 and σ phases, are fabricated without changing the overall chemistry or composition. More interestingly, hexagonally close-packed spherical phase becomes thermodynamically stable and experimentally accessible attributed to the synergistic contribution of the two end blocks. The shorter A blocks are pulled out from the core domain into the matrix to release packing frustration, while the longer ones stabilize the ordered spherical phase against composition fluctuation that tends to disrupt the lattice. This study adds a missing puzzle piece to the block copolymer phase diagram and provides a robust approach for rational structural engineering.

Single cell analyses reveal the PD-1 blockade response-related immune features in hepatocellular carcinoma.

Background: Immunotherapy has demonstrated its potential to improve the prognosis of patients with hepatocellular carcinoma (HCC); however, patients' responses to immunotherapy vary a lot. A comparative analysis of the tumor microenvironment (TME) in responders and non-responders is expected to unveil the mechanisms responsible for the immunotherapy resistance and provide potential treatment targets. Methods: We performed sequencing analyses using 10x Genomics technology on six HCC patients who responded to anti-PD-1 therapy and one HCC patient who did not respond. Additionally, we obtained single cell data from untreated, responsive, and nonresponsive HCC patients from public databases, and used part of the datasets as a validation cohort. These data were integrated using algorithms such as Harmony. An independent validation cohort was established. Furthermore, we performed spatial transcriptomic sequencing on the tumor adjacent tissues of three HCC responsive patients using 10x Genomics spatial transcriptomic technology. Additionally, we analyzed data about three HCC patients obtained from public databases. Finally, we validated our conclusions using immunofluorescence, flow cytometry, and in vivo experiments. Results: Our findings confirmed the presence of "immune barrier" partially accounting for the limited efficacy of immunotherapy. Our analysis revealed a significant increase in TREM2+ Macrophages among non-responsive patients expressing multiple immunosuppressive signals. anti-Csf1r monoclonal antibodies effectively eliminated these macrophages and augmented the therapeutic effects of anti-PD-1 therapy. TCR+ Macrophages possessed direct tumor-killing capabilities. IL1B+ cDC2 was the primary functional subtype of cDC2 cells. Absence of THEMIShi CD8+ T subtypes might diminish immunotherapeutic effects. Furthermore, CD8+ T cells entered a state of stress after anti-PD-1 treatment, which might be associated with CD8+ T cell exhaustion and senescence. Conclusions: The profiles of immune TMEs showed differences in HCC patients responsive, non-responsive and untreated. These differences might explain the discounted efficacy of immunotherapy in some HCC patients. The cells and molecules, which we found to carry unique capabilities, may be targeted to enhance immunotherapeutic outcomes in patients with HCC.

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a familiar critical disease in the intensive care unit (ICU) patients. Nursing staff are important spiritual pillars during the treatment of patients, and in addition to routine nursing, more attention needs be paid to the patient's psychological changes. AIM: To investigate the effects of psychological intervention in ICU patients with SAP. METHODS: One hundred ICU patients with SAP were hospitalized in the authors' hospital between 2020 and 2023 were selected, and divided into observation and control groups per the hospitalization order. The control and observation groups received routine nursing and psychological interventions, respectively. Two groups are being compared, using the Self-rating Anxiety Scale (SAS), Self-Determination Scale (SDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and 36-item Short Form Health Survey (SF-36) scores; nursing satisfaction of patients; ICU care duration; length of stay; hospitalization expenses; and the incidence of complications. RESULTS: After nursing, the SDS, SAS, and APACHE II scores in the experimental group were significantly lower than in the control group (P < 0.05). The SF-36 scores in the observation group were significantly higher than those in the control group (P < 0.05). The nursing satisfaction of patients in the experimental group was 94.5%, considerably higher than that of 75.6% in the control group (P < 0.05). The ICU care duration, length of stay, and hospitalization expenses in the observation group were significantly lower than those in the control group, and the incidence of complications was lower (P < 0.05). CONCLUSION: For patients with SAP, the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

Characteristics and trends in adverse drug reactions in Ghana-evidence of spontaneous reports, 2005-2021.

BACKGROUND: Adverse drug reaction (ADR) monitoring is crucial in ensuring patient and pharmaceutical safety. However, there is a lack of evidence regarding ADR reporting trend pattern in Ghana. This study, therefore, aimed to analyse and characterise trends in ADRs reported in Ghana over 16 years. METHODS: We retrospectively analysed individual case safety retorts (ICSRs) received by the Ghana National Pharmacovigilance Centre from 2005 to 2021. Jointpoint regression was used to estimate age-adjusted ADR rates, stratified by sex and patient characteristics, suspected medication groups, clinical indications, and the manifestation of ADRs. To evaluate trends over time, the percentage annualised estimator was used. RESULTS: We identified a total of 6853 ICSRs from 2005 to 2021. The age-adjusted ICSR rates increased significantly from 2005 to 2019, with an annual increase of 18.6%; however, there was a downward trend from 2019 to 2021, although not statistically significant. Males accounted for the majority (64.3%) of ICSRs compared to females (35.7%). The suspected medication group most frequently associated with ADRs were antiprotozoals accounting for 35.6% of all ICSRs, while vascular disorders (21.0%) were the most commonly observed clinical indication in relation to ADRs. An increase in ICSR rates was noted for gastrointestinal disorders with an annual increase of 32.5% (95% CI, 20.6-45.6%; p < 0.001). Amodiaquine was the most commonly suspected medication (8.9%) associated with ADRs, while pruritus (7.2%) was the most frequently reported preferred term. CONCLUSION: The study provides a detailed overview of ICSRs received by the Ghana National Pharmacovigilance Centre over the past 16 years and demonstrates an increasing trend of ADR-related medication use as well as clinical indications over time. The findings of this study call for multifaceted strategies aimed at reducing the risks associated with inappropriate drug use, and enhancing knowledge of medication safety, thus improving healthcare service delivery and patient safety.

Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1.

Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification.

Effects of nutritional interventions on cognitive function in adult cancer survivors: A systematic review.

AIM: To evaluate the effectiveness and safety of nutritional interventions (i.e. nutritional support, dietary patterns and dietary supplements) on cognitive function in cancer survivors. DESIGN: Systematic review. METHODS: A systematic and comprehensive search of PubMed, Web of Science, the Cochrane Library, Embase, and CINAHL was conducted from the inception until March 10, 2023. The last search was conducted on December 10, 2023. REPORTING METHOD: PRISMA. RESULTS: A total of 59 randomized controlled trials were included for analysis. Nutritional support, dietary patterns and dietary supplements improved cognitive function in cancer survivors with no apparent safety concerns. The anti-inflammatory diet, the fasting-mimicking diet and the web-based diet significantly improved cognitive function. Whereas the ketogenic diet or dietary advice to consume more soluble dietary fibres and less insoluble dietary fibres and lactose could not. There was evidence from dietary supplements to support the beneficial effects of polyunsaturated fatty acid supplements, traditional herbal medicines and other supplements. CONCLUSIONS: Nutritional interventions have great promise for improving cognitive function in adult cancer survivors. Further validation of the nutritional interventions supported in this study in other survivors and exploration of more effective nutritional interventions are needed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This work can support the construction of nutritional support interventions and dietary guidance programs to prevent cancer-related cognitive decline. IMPACT: This work filled a gap in preventive strategies for cancer-related cognitive decline from a nutritional perspective. Nutritional support, dietary patterns, and dietary supplements can prevent cancer-related cognitive decline without serious safety concerns. This work highlighted nutritional interventions that have the potential to improve cognitive function in cancer survivors, benefiting the further construction of evidence-based nutritional intervention programs. PROTOCOL REGISTRATION: PROSPERO. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The 3d-4f electron transition of the CoS2/CeO2 heterojunction for efficient oxygen evolution.

CoS2/CeO2, exhibiting the 3d-4f orbital coupling effect, is developed and shows exceptional OER activity, with an overpotential of 140 mV at 10 mA cm-2. DFT calculation and Raman spectra show the existence of a d-p-f electron transport ladder that can accelerate electron transfer through the Co-O(S)-Ce bond, optimize the adsorption free energy, and enhance the catalytic activity.

Impact of urban and rural residents medical insurance on self-rated health of residents in China: a panel study from the China family panel studies national baseline survey.

Objective: This study aimed to investigate the health performance of the Urban and Rural Residents Medical Insurance (URRMI) scheme in China and to make practical recommendations and scientific references for its full implementation in China. Methods: This is a panel study that uses data from the China Family Panel Studies from 2018 to 2020, which is separated into treated and control groups each year, utilizing the key approach of propensity score matching and difference-in-difference (PSM-DID). Using 1-to-1 k-nearest neighbor matching, we proportionate the baseline data. Using difference-in-difference model, we examine the mean treatment impact of the outcome variables. Using a 500-time random sample regression model, we validate the robustness of the model estimation. Results: The result was credible after matching, minimizing discrepancies. Good overall performance of self-rated health with an average Hukou status of, respectively, 0.8 and 0.4 in the treated and control group, primarily in rural and urban regions separately. The participation of URRMI significantly impacted self-rated health of residents, with a 0.456-unit improvement probabilities observed (p < 0.1). Additionally, the individuals are categorized into urban and rural, and those with urban hukou had a 0.311 expansion in the probability of having better health status compared to rural hukou (p < 0.05). Other factors, such as age, highest education, annual income, medical expenditure, hospital scale, clinic satisfaction, and napping, also impacted self-rated health. Moreover, elder individuals, higher education levels, and higher medical expenditure having a higher probability of improvement. The study utilized a placebo test to verify the robustness of the URRMI regression. The estimated coefficients showed that basic medical insurance did not significantly improve the health of insured residents under the URRMI scheme. Conclusion: The study demonstrates the crucial role of PSM-DID in determining the influence of URRMI on self-rated health status. It indicates that purchasing in URRMI has a favorable influence on the health of residents, advancing enhanced self-rated health effectiveness. It does, however, reveal geographical disparities in health, with urban dwellers faring far better than those who live in the suburb. Study suggests expanding URRMI coverage, narrowing urban-rural divide, increasing insurance subsidies, reforming laws, and developing effective advertising strategies.

Liraglutide Improves Myocardial Perfusion and Energetics and Exercise Tolerance in Patients With Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. OBJECTIVES: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. METHODS: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m2) [95% CI: 26.1-29.5 kg/m2)]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. RESULTS: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009). CONCLUSIONS: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939).

Twenty-five years of research on resting-state fMRI of major depressive disorder: A bibliometric analysis of hotspots, nodes, bursts, and trends.

Major depressive disorder (MDD) is a debilitating mental health condition that poses significant risks and burdens. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a promising tool in investigating the neural mechanisms underlying MDD. However, a comprehensive bibliometric analysis of resting-state fMRI in MDD is currently lacking. Here, we aimed to thoroughly explore the trends and frontiers of resting-state fMRI in MDD research. The relevant publications were retrieved from the Web of Science database for the period between 1998 and 2022, and the CiteSpace software was employed to identify the influence of authors, institutions, countries/regions, and the latest research trends. A total of 1501 publications met the search criteria, revealing a gradual increase in the number of annual publications over the years. China contributed the largest publication output, accounting for the highest percentage among all countries. Particularly, the University of Electronic Science and Technology of China, Capital Medical University, and Harvard Medical School were identified as key institutions that have made substantial contributions to this growth. Neuroimage, Biological Psychiatry, Journal of Affective Disorders, and Proceedings of the National Academy of Sciences of the United States of America are among the influential journals in the field of resting-state fMRI research in MDD. Burst keywords analysis suggest the emerging research frontiers in this field are characterized by prominent keywords such as dynamic functional connectivity, cognitive control network, transcranial brain stimulation, and childhood trauma. Overall, our study provides a systematic overview into the historical development, current status, and future trends of resting-state fMRI in MDD, thus offering a useful guide for researchers to plan their future research.