Association of household chemicals use with cognitive function among Chinese older adults.

Background: The paucity of empirical evidence supporting a correlation between the utilization of household chemicals and cognitive decline in Chinese older adults. Methods: The data utilized for this study originated from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 2018). Using regression models to investigate the relationship between exposure to household chemicals and cognitive decline, and evaluate the impact of different fields on cognitive function. Results: The use of household chemicals was associated with a decline in cognitive function (anti-caries agent, OR = 1.68, P = 0.040; air freshener, OR = 2.48, P = 0.002; disinfectant, OR = 1.40, P = 0.033). The more frequent the use of household chemicals, the worse the cognitive function (Model1: OR = 2.54, P = 0.024; Model2: OR = 3.23, P = 0.006; Model3: OR = 3.59, P = 0.003). Conclusion: The study has uncovered a correlation between the utilization of household chemicals and cognitive decline in individuals aged 65 years and over in China.

Preoperative CT-based intra- and peri-tumoral radiomic models for differentiating benign and malignant tumors of the parotid gland: a two-center study.

OBJECTIVE: To investigate the ability of intra- and peritumoral radiomics based on three-phase computed tomography (CT) to distinguish between malignant and benign parotid tumors. METHODS: We conducted a retrospective analysis of data from 374 patients with parotid gland tumors, all confirmed by histopathology. A total of 321 patients from Center 1 (January 2014 to January 2023) were randomly divided into the training set and internal testing set at a ratio of 7:3, whereas 53 patients from Center 2 (January 2020 to June 2022) constituted the external testing set. CT images of both the tumor and surrounding areas (2 mm and 5 mm areas surrounding the tumor) were reviewed, and their radiomic features were extracted for the construction of different radiomic models. In addition, a combined clinical-radiomic model was developed using multivariate logistic regression analysis. The model's predictive performance was evaluated using decision curve analysis (DCA) and receiver operating characteristic (ROC) curves. RESULTS: Among the models evaluated, Tumor + External2 model demonstrated superior predictive performance. The areas under the curve (AUCs) of this model were 0.986 in the training set, 0.827 in the internal test set, and 0.749 in the external test set. For the clinical model, independent predictive factors included symptoms, boundaries, and lymph node swelling. The combined clinical-radiomic model achieved AUCs of 0.981, 0.842, and 0.749 in the three cohorts, outperforming both the Tumor model and the clinical model individually. CONCLUSION: The CT-based radiomic models incorporating intratumoral and peritumoral radiomic features can effectively distinguish malignant from benign parotid tumors, and the predictive accuracy is further improved by incorporating clinically independent predictors.

Interactions between feed protein source and feeding frequency on growth performance and health status of largemouth bass (Micropterus salmoides).

In order to evaluate the effects of the interaction between different proteins and feeding frequency on largemouth bass (Micropterus salmoides) and to provide scientific guidance for the application of novel proteins and the corresponding optimal feeding strategy, a two-factorial design (5 × 3) with five protein feeds (fishmeal (FM), Clostridium autoethanogenum protein (CAP), Tenebrio molitor (TM), Chlorella meal (ChM), cottonseed protein concentrate (CPC)), and three feeding frequency (1, 2, and 3 times/d; FF1, FF2, FF3) was designed in culturing largemouth bass (initial weight, 2.98 ± 0.22 g/fish) for 8 weeks. Z-score combined with cluster analysis was used to analyze and compare the effects of different treatments on different indicators, such as growth performance, feed utilization, antioxidant capacity, and immune response to draw a general picture of the relationship among all these massive biomarkers. The results showed that different protein sources and feeding frequencies had significant interactive effects on growth performance, feed utilization efficiency, body lipid, and health status of largemouth bass. Fish fed with ChM feed showed similar performance to that in FM group, implying its potential for complete replacement of fishmeal in largemouth bass. Fish fed with CAP, TM, and CPC feeds showed worse performance compared to FM and ChM groups, characterized by poor growth and feed utilization, enhanced stress, chronic inflammation, and varying symptoms of histological changes in the liver and intestine, which demonstrated the adverse effects of the complete replacement of fishmeal by these three proteins. In terms of feeding frequency, fish fed with FM feed in FF3 group led to liver hypertrophy, fat accumulation, and the risk of fatty liver, while inducing liver inflammation. In addition, the TM and CAP group had the higher expression levels of inflammatory factors at FF3 group, which displayed that the interactions between FM, CAP, TM feeds and feeding frequency at FF3 might aggravate the occurrence of liver inflammation and oxidative damage of hepatocytes. Overall, FF2 had higher feed efficiency, protein efficiency, antioxidant enzyme and lysozyme activities, lower MDA content, and lower gene expression of inflammatory cytokines and could be considered as the optimum feeding frequency for largemouth bass fed with different protein feeds.

Construction of MIL-100(Fe)-DMA material for efficient adsorption of Sr and Cs ions from radioactive wastewater.

A novel metal-organic framework (MOF) material, MIL-100(Fe)-DMA, was synthesized using the solvothermal method. The structure of the MOF was characterized using scanning electron microscopy-energy dispersive X-ray spectroscopy, N2 adsorption-desorption isotherms, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Mössbauer spectroscopy. Batch adsorption experiments were performed to investigate the effects of initial Sr2+ and Cs+ concentrations, adsorption time, pH, and coexisting cations on the adsorption performance of the material. The adsorption mechanism was further elucidated using adsorption kinetics and isotherm models. The results indicated that the adsorption of Sr2+ and Cs+ does not significantly affect the MOF material structure. As reaction time and initial ion concentration increased, the adsorption capacity of MIL-100(Fe)-DMA for Sr2+ and Cs+ increased rapidly and then gradually reached equilibrium. Optimal adsorption occurred under alkaline conditions, with maximum adsorption capacity observed at pH = 8. The adsorption process for Sr2+ and Cs+ was well described by the pseudo-second-order kinetic model, the Weber-Morris model, and the Langmuir adsorption isothermal model. The adsorption process was mainly identified as monolayer chemical adsorption, influenced by multiple factors. Characterization combined with density functional theory calculations revealed that the unsaturated carboxylic acid groups on the surface of the MOFs play a crucial role in the interaction with Sr2+ and Cs+.

Deprescribing of Antihypertensive Medications and Cognitive Function in Nursing Home Residents.

Importance: Antihypertensive medication deprescribing is common among nursing home residents, yet its association with cognitive decline remains uncertain. Objective: To investigate the association of deprescribing antihypertensive medication with changes in cognitive function in nursing home residents. Design, Setting, and Participants: This cohort study using a target trial emulation approach included VA long-term care residents aged 65 years or older with stays of at least 12 weeks from 2006 to 2019. Residents who were not prescribed antihypertensive medication, with blood pressure greater than 160/90 mm Hg, or with heart failure were excluded. Eligible residents with stable medication use for 4 weeks were classified into deprescribing or stable user groups and followed for 2 years or until death or discharge for intention-to-treat (ITT) analysis. Participants switching treatment groups were censored in the per-protocol analysis. Cognitive function measurements during follow-up were analyzed using an ordinal generalized linear mixed model, adjusting for confounders with inverse probability of treatment weighting. Per-protocol analysis included inverse probability of censoring weighting. Data analyses were performed from May 1, 2023, and July 1, 2024. Exposures: Deprescribing was defined as a reduction in the total number of antihypertensive medications or a decrease in medication dosage by 30%, sustained for a minimum of 2 weeks. Main Outcomes and Measures: Cognitive Function Scale (CFS) was classified as cognitively intact (CFS = 1), mildly impaired (CFS = 2), moderately impaired (CFS = 3), and severely impaired (CFS = 4). Results: Of 45 183 long-term care residents, 12 644 residents (mean [SD] age 77.7 [8.3] years; 329 [2.6%] females and 12 315 [97.4%] males) and 12 053 residents (mean [SD] age 77.7 [8.3] years; 314 [2.6%] females and 11 739 [97.4%] males) met eligibility for ITT and per-protocol analyses, respectively. At the end of the follow-up, 12.0% of residents had a worsened CFS (higher score) and 7.7% had an improved CFS (lower score) with 10.8% of the deprescribing group and 12.1% of the stable user group showing a worsened CFS score. In the per-protocol analysis, the deprescribing group had a 12% reduction in the odds of progressing to a worse CFS category per 12-week period (odds ratio, 0.88; 95% CI, 0.78-0.99) compared to the stable user group. Among residents with dementia, deprescribing was associated with 16% reduced odds of cognitive decline (odds ratio, 0.84; 95% CI, 0.72-0.98). These patterns remained consistent in the ITT analysis. Conclusions and Relevance: This cohort study indicates that deprescribing is associated with less cognitive decline in nursing home residents, particularly those with dementia. More data are needed to understand the benefits and harms of antihypertensive deprescribing to inform patient-centered medication management in nursing homes.

Structural changes of wheat starch and activity inhibition of α-glucosidase by persimmon (Diospyros kaki Thunb.) leaves extract retarding starch digestibility.

Elevated blood sugar levels caused by starch digestion was a target for controlling diabetes mellitus. The in vitro and in vivo digestibility of wheat starch was evaluated to find that adding 15 % persimmon leaf extract (PLE) to starch reduced its digestibility by 69.50 % and the peak postprandial blood glucose by 23.63 %. Subsequently, we observed under scanning electron microscopy and atomic force microscopy that the presence of PLE led to the destruction of starch structure and the aggregation of α-glucosidase so as to decrease starch digestion and hinder the binding of starch to α-glucosidase. Through multi-spectral analysis, PLE hindered the clathrate of iodine and starch, and also increased the crystallinity of starch by 48.58 %. For α-glucosidase inhibitory activity (IC50 = 72.49 µg/mL), PLE preferentially occupied the active center of α-glucosidase, changed its fluorescence characteristics and secondary structure through hydrogen bonding and hydrophobic interaction. Moreover, among the 23 potential α-glucosidase inhibitors screened from PLE, combined with molecular simulation, Procyanidin B2 had the strongest inhibitory effect (IC50 = 33.22 µg/mL) and binding energy (-7.09 kcal/mol), which was most effectively inhibitory on digestion. These results indicated the potential of PLE in hypoglycemia targeting both starch and α-glucosidase.

Microscopic Insight into the Polarization-Dependent Oxygen Evolution Reaction on the Surface of Intrinsic Ferroelectric Semiconductor ß-CuGaO2.

Ferroelectric semiconductors hold great promise in the field of photocatalysis due to their spontaneous polarization that can suppress the recombination of photogenerated charges, but the mechanism of the effect of ferroelectric polarization and the intensity of polarization on surface catalytic reactions have never been approached. Here, we have comparatively investigated the oxygen evolution reaction (OER) catalytic process on surfaces in polarized and unpolarized orientations of the intrinsic ferroelectric semiconductor ß-CuGaO2 by first-principles calculations. Furthermore, semiquantitative effects of different polarization intensities on the OER on the surfaces are subsequently carried out. First, it is confirmed that the [011]-polarized surface with fully exposed Cu-O atoms is the easiest surface to form and the most attractive for water molecules, exhibiting the lowest OER free energy barrier of 1.71 eV. Second, the calculated results indicate that [011] surfaces with higher polarization intensity are capable of enhancing the photogenerated hole potential (U) due to the accumulation of microscopic polarization in the polar unit of the bulk phase within the [011] slab. The intrinsic mechanism behind the enhancement of the OER by ferroelectric polarization is attributed to the modulation effect of polarization intensity on the 3d orbit of Cu+. This work elucidates the effects of ferroelectric polarization orientations as well as polarization intensity for the water OER, and provides theoretical guidance for the intrinsic ferroelectric polarization to promote surface OER.

Response and disease resistance evaluation of sorghum seedlings under anthracnose stress.

Sorghum is the world's fifth-largest cereal crop, and anthracnose (Colletotrichum sublineola) is the main disease affecting sorghum. However, systematic research on the cellular structure, physiological and biochemical, and genes related to anthracnose resistance and disease resistance evaluation in sorghum is lacking in the field. Upon inoculation with anthracnose (C. sublineola) spores, disease-resistant sorghum (gz93) developed a relative lesion area (RLA) that was significantly smaller than that of the disease-susceptible sorghum (gz234). The leaf thickness, length and profile area of leaf mesophyll cells, upper and lower epidermal cells decreased in the lesion area, with a greater reduction observed in gz234 than in gz93. The damage caused by C. sublineola resulted in a greater decrease in the net photosynthetic rate (Pn) in gz234 than in gz93, with early-stage reduction due to stomatal limitation and late-stage reduction caused by lesions. Overall, the activities of superoxide dismutase (SOD) and catalase (CAT), the content of proline (Pro), abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and gibberellic acid (GA3), are higher in gz93 than in gz234 and may be positively correlated with disease resistance. While malondialdehyde (MDA) may be negatively correlated with disease resistance. Disease-resistant genes are significantly overexpressed in gz93, with significant expression changes in gz234, which is related to disease resistance in sorghum. Correlation analysis indicates that GA3, MDA, peroxidase (POD), and disease-resistance genes can serve as reference indicators for disease severity. The regression equation RLA = 0.029 + 8.02 × 10-6 JA-0.016 GA3 can predict and explain RLA. Principal component analysis (PCA), with the top 5 principal components for physiological and biochemical indicators and the top 2 principal components for disease-resistant genes, can explain 82.37% and 89.11% of their total variance, reducing the number of evaluation indicators. This study provides a basis for research on the mechanisms and breeding of sorghum with resistance to anthracnose.

Lesion region inpainting: an approach for pseudo-healthy image synthesis in intracranial infection imaging.

The synthesis of pseudo-healthy images, involving the generation of healthy counterparts for pathological images, is crucial for data augmentation, clinical disease diagnosis, and understanding pathology-induced changes. Recently, Generative Adversarial Networks (GANs) have shown substantial promise in this domain. However, the heterogeneity of intracranial infection symptoms caused by various infections complicates the model's ability to accurately differentiate between pathological and healthy regions, leading to the loss of critical information in healthy areas and impairing the precise preservation of the subject's identity. Moreover, for images with extensive lesion areas, the pseudo-healthy images generated by these methods often lack distinct organ and tissue structures. To address these challenges, we propose a three-stage method (localization, inpainting, synthesis) that achieves nearly perfect preservation of the subject's identity through precise pseudo-healthy synthesis of the lesion region and its surroundings. The process begins with a Segmentor, which identifies the lesion areas and differentiates them from healthy regions. Subsequently, a Vague-Filler fills the lesion areas to construct a healthy outline, thereby preventing structural loss in cases of extensive lesions. Finally, leveraging this healthy outline, a Generative Adversarial Network integrated with a contextual residual attention module generates a more realistic and clearer image. Our method was validated through extensive experiments across different modalities within the BraTS2021 dataset, achieving a healthiness score of 0.957. The visual quality of the generated images markedly exceeded those produced by competing methods, with enhanced capabilities in repairing large lesion areas. Further testing on the COVID-19-20 dataset showed that our model could effectively partially reconstruct images of other organs.

Plant diversity enhances ecosystem multifunctionality via multitrophic diversity.

Ecosystem functioning depends on biodiversity at multiple trophic levels, yet relationships between multitrophic diversity and ecosystem multifunctionality have been poorly explored, with studies often focusing on individual trophic levels and functions and on specific ecosystem types. Here, we show that plant diversity can affect ecosystem functioning both directly and by affecting other trophic levels. Using data on 13 trophic groups and 13 ecosystem functions from two large biodiversity experiments-one representing temperate grasslands and the other subtropical forests-we found that plant diversity increases multifunctionality through elevated multitrophic diversity. Across both experiments, the association between multitrophic diversity and multifunctionality was stronger than the relationship between the diversity of individual trophic groups and multifunctionality. Our results also suggest that the role of multitrophic diversity is greater in forests than in grasslands. These findings imply that, to promote sustained ecosystem multifunctionality, conservation planning must consider the diversity of both plants and higher trophic levels.

The yellowhorn MYB transcription factor MYB30 is required for wax accumulation and drought tolerance.

Yellowhorn (Xanthoceras sorbifolium Bunge) is an economically important tree species in northern China, mainly distributed in arid and semi-arid areas where water resources are scarce. Drought affects its yield and the expansion of its suitable growth area. It was found that the wax content in yellowhorn leaves varied significantly among different germplasms, which had a strong correlation with the drought resistance of yellowhorn. In this study, XsMYB30 was isolated from 'Zhongshi 4' of yellowhorn, a new highly waxy variety. DAP-Seq technology revealed that the pathways associated with fatty acids were significantly enriched in the target genes of XsMYB30. Moreover, the results of electrophoretic mobility shift assay, yeast one hybrid assay and dual-luciferase assay demonstrated that XsMYB30 could directly and specifically bind with the promoters of genes involved in wax biosynthesis (XsFAR4, XsCER1 and XsKCS1), lipid transfer (XsLTPG1 and XsLTP1) and fatty acid synthesis (XsKASIII), thus enhancing their expression. In addition, the overexpression of XsMYB30 in poplar promoted the expression levels of these target genes and increased the wax deposition on poplar leaves leading to a notable improvement in the plant's ability to withstand drought. These findings indicate that XsMYB30 is an important regulatory factor in cuticular wax biosynthesis and the drought resistance of yellowhorn.

Ruthenium Anchored Laser-Induced Graphene as Binder-Free and Free-Standing Electrode for Selective Electrosynthesis of Ammonia from Nitrate.

Developing effective electrocatalysts for the nitrate reduction reaction (NO3RR) is a promising alternative to conventional industrial ammonia (NH3) synthesis. Herein, starting from a flexible laser-induced graphene (LIG) film with hierarchical and interconnected macroporous architecture, a binder-free and free-standing Ru-modified LIG electrode (Ru-LIG) is fabricated for electrocatalytic NO3RR via a facile electrodeposition method. The relationship between the laser-scribing parameters and the NO3RR performance of Ru-LIG electrodes is studied in-depth. At -0.59 VRHE, the Ru-LIG electrode exhibited the optimal and stable NO3RR performance (NH3 yield rate of 655.9 µg cm-2 h-1 with NH3 Faradaic efficiency of up to 93.7%) under a laser defocus setting of +2 mm and an applied laser power of 4.8 W, outperforming most of the reported NO3RR electrodes operated under similar conditions. The optimized laser-scribing parameters promoted the surface properties of LIG with increased graphitization degree and decreased charge-transfer resistance, leading to synergistically improved Ru electrodeposition with more exposed NO3RR active sites. This work not only provides a new insight to enhance the electrocatalytic NO3RR performance of LIG-based electrodes via the coordination with metal electrocatalysts as well as identification of the critical laser-scribing parameters but also will inspire the rational design of future advanced laser-induced electrocatalysts for NO3RR.

Complex Patterns of Antihypertensive Treatment Changes in Long-Term Care Residents.

OBJECTIVES: Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 24,870 Department of Veterans Affairs (VA) nursing home residents aged ≥65 years with long-term stays (≥180 days) from 2006 to 2019. METHODS: We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission. RESULTS: More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years). CONCLUSIONS AND IMPLICATIONS: Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes.

Technology of plant factory for vegetable crop speed breeding.

Sustaining crop production and food security are threatened by a burgeoning world population and adverse environmental conditions. Traditional breeding methods for vegetable crops are time-consuming, laborious, and untargeted, often taking several years to develop new and improved varieties. The challenges faced by a long breeding cycle need to be overcome. The speed breeding (SB) approach is broadly employed in crop breeding, which greatly shortens breeding cycles and facilities plant growth to obtain new, better-adapted crop varieties as quickly as possible. Potential opportunities are offered by SB in plant factories, where optimal photoperiod, light quality, light intensity, temperature, CO2 concentration, and nutrients are precisely manipulated to enhance the growth of horticultural vegetable crops, holding promise to surmount the long-standing problem of lengthy crop breeding cycles. Additionally, integrated with other breeding technologies, such as genome editing, genomic selection, and high-throughput genotyping, SB in plant factories has emerged as a smart and promising platform to hasten generation turnover and enhance the efficiency of breeding in vegetable crops. This review considers the pivotal opportunities and challenges of SB in plant factories, aiming to accelerate plant generation turnover and improve vegetable crops with precision and efficiency.

Cluster of Differentiation 36 (CD36) Preferentially Mediates Intestinal Absorption of Dietary Z-Astaxanthin and Especially 9-Z-Isomer via Higher Binding Affinity.

Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.

Systematic analysis of the expression profiles and prognostic significance of the MED gene family in renal clear cell carcinoma.

The mediator complex (MED) family is a contributing factor in the regulation of transcription and proliferation of cells, and is closely associated with the development of various types of cancer. However, the significance of the expression levels and prognostic value of MED genes in kidney renal clear cell carcinoma (KIRC) have rarely been reported. The present study analyzed the expression and prognostic potential of MED genes in KIRC. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network (PPI), the Assistant for Clinical Bioinformatics database was used to perform correlation analysis, GEPIA 2 was utilized to draw the Kaplan-Meier plot and analyze prognostic significance and the Tumor Immune Estimation Resource was used to assess the association of MED genes with the infiltration of immune cells in patients with KIRC. A total of 30 MED genes were identified, and among these genes, 11 were selected for the creation of a prognostic gene signature based on the results of a LASSO Cox regression analysis. Furthermore, according to univariate and multivariate analyses, MED7, MED16, MED21, MED25 and MED29 may be valuable independent predictive biomarkers for the prognosis of individuals with KIRC. Furthermore, there were significant differences in the expression levels of MED7, MED21 and MED25 in KIRC among different tumor grades. Additionally, patients with KIRC with high transcription levels of MED7, MED21 and MED29 had considerably longer overall survival times. The expression levels of MED genes were also linked to the infiltration of several immune cells. Overall, MED genes may have potential significance in predicting the prognosis of patients with KIRC.

Effects of xenogeneic transplantation of umbilical cord-derived mesenchymal stem cells combined with irbesartan on renal podocyte damage in diabetic rats.

BACKGROUND: The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. METHODS: A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 106 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. RESULTS: The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. CONCLUSIONS: Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.

Interaction analysis of RNA G-quadruplex with ligands and in situ imaging application.

RNA G4, as an integral branch of G4 structure, possesses distinct interactions with ligands compared to the common DNA G4, thus the investigation of RNA G4/ligand interactions might be considered as a fresh breakthrough to improve the biosensing performance of G4/ligand system. In this study, we comparatively explored the structural and functional mechanisms of RNA G4 and DNA G4 in the interaction with ligands, hemin and thioflavin T (ThT), utilizing the classical PS2.M sequence as a model. We found that although the catalytic performance of RNA G4/hemin system was lower than DNA G4/hemin, RNA G4/ThT fluorescence system exhibited a significant improvement (2∼3-fold) compared to DNA G4/ThT, and adenine modification could further enhance the signaling. Further, by exploring the interaction between RNA G4 and ThT, we deemed that RNA G4 and ThT were stacked in a bimolecular mode compared to single-molecule binding of DNA G4/ThT, thus more strongly limiting the structural spin in ThT excited state. Further, RNA G4/ThT displayed higher environmental tolerance and lower ion dependence than DNA G4/ThT. Finally, we employed RNA G4/ThT as a highly sensitive label-free fluorescent signal output system for in situ imaging of isoforms BCR-ABL e13a2 and e14a2. Overall, this study successfully screened a high-performance RNA G4 biosensing system through systematic RNA G4/ligands interaction studies, which was expected to provide a promising reference for subsequent G4/ligand research.

Enhanced choroid plexus segmentation with 3D UX-Net and its association with disease progression in multiple sclerosis.

BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.