Modeling refined differences of cortical folding patterns via spatial, morphological, and temporal fusion representations.

The gyrus, a pivotal cortical folding pattern, is essential for integrating brain structure-function. This study focuses on 2-Hinge and 3-Hinge folds, characterized by the gyral convergence from various directions. Existing voxel-level studies may not adequately capture the precise spatial relationships within cortical folding patterns, especially when relying solely on local cortical characteristics due to their variable shapes and homogeneous frequency-specific features. To overcome these challenges, we introduced a novel model that combines spatial distribution, morphological structure, and functional magnetic resonance imaging data. We utilized spatio-morphological residual representations to enhance and extract subtle variations in cortical spatial distribution and morphological structure during blood oxygenation, integrating these with functional magnetic resonance imaging embeddings using self-attention for spatio-morphological-temporal representations. Testing these representations for identifying cortical folding patterns, including sulci, gyri, 2-Hinge, and 2-Hinge folds, and evaluating the impact of phenotypic data (e.g. stimulus) on recognition, our experimental results demonstrate the model's superior performance, revealing significant differences in cortical folding patterns under various stimulus. These differences are also evident in the characteristics of sulci and gyri folds between genders, with 3-Hinge showing more variations. Our findings indicate that our representations of cortical folding patterns could serve as biomarkers for understanding brain structure-function correlations.

A novel Bacillus aerolatus CX253 attenuates inflammation induced by Streptococcus pneumoniae in childhood and pregnant rats by regulating gut microbiome.

Streptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17% of pregnant women. However, no more effective measures exist to prevent infection induced by Spn in these two special populations. The beneficial microbes can antagonize Spn and provide new targets for preventing pneumococcal infections. This study used 16S rRNA gene sequencing and targeted metabolomics to evaluate the role of the Bacillus aerolatus CX253 (CX253) in alleviating Spn infection. Additionally, the colonization of CX253 was observed in nose, trachea, and lung by using confocal laser scanning microscopy and fluorescent labeling techniques. Compared with the model group, the expression level of interleukin-1ß was dropped 1.81-fold and 2.22-fold, and interleukin-6 was decreased 2.39-fold and 1.84-fold. The express of tumor necrosis factor-α was down 2.30-fold and 3.84-fold in prevention group of childhood and pregnant rats, respectively. The 16S rRNA sequencing results showed that CX253 administration alone significantly increased the abundance of Lactobacillus, Limosilactobacillus, and Prevotella in the gut of childhood and pregnant rats. Furthermore, the CX253 increased propionate in the gut of childhood rats and increased propionate and butyrate in the gut of pregnant rats to inhibit pulmonary inflammation. In summary, CX253 attenuated Spn-induced inflammation by regulating the gut microbiota and SCFAs. The research provides valuable information for the prevention of pneumonia.

Ultrabright NIR-II Nanoprobe for Image-Guided Accurate Resection of Tiny Metastatic Lesions.

Fluorescence imaging is a vital way to delineate the tumor boundaries. Here, we achieve a NIR-II aggregation-induced emission luminogen (AIEgen) with a fluorescence quantum yield (QY) of 12.6% in water through straightforward alkyl side chain modification. After loading of NIR-II AIEgen into polystyrene (PS) nanospheres, the thermal deactivation pathway is extremely limited, thereby concentrating absorption excitation on fluorescence emission. The fluorescence intensity is further enhanced by 5.4 times, the QY increases to 21.1%, and the NIR-II imaging signal is accordingly enhanced by 8.7 times, surpassing conventional DSPE-PEG carriers. The NIR-II@PS nanoprobe showcases superior resolution and tissue penetration depth compared to indocyanine green (ICG) and short-range near-infrared AIEgens. In vivo investigations underscore its tumor-to-normal tissue ratio (3.9) at 24 h post intravenous injection, enabling complete resection of ≤1 mm metastases under NIR-II bioimaging guidance. Additionally, the PS carrier-nanoparticles exhibit low toxicity in vivo, laying a promising foundation for the future design of medical nanomaterials.

Inhibition of Cardiac Kv4.3/KChIP2 Channels by Sulfonylurea Drug Gliquidone.

The Kv4.3 channel features fast N-type inactivation and also undergoes a slow C-type inactivation. The gain-of-function mutations of Kv4.3 channels cause an inherited disease called Brugada syndrome (BrS), characterized by a shortened duration of cardiac action potential repolarization and ventricular arrhythmia. The sulfonylurea drug gliquidone, an ATP-dependent K+ channel antagonist, is widely used for the treatment of type 2 diabetes. Here, we report a novel role of gliquidone in inhibiting Kv4.3 and Kv4.3/KChIP2 channels that encode the cardiac transient outward K+ currents responsible for the initial phase of action potential repolarization. Gliquidone results in concentration-dependent inhibition of both Kv4.3 and Kv4.3/KChIP2 fast or steady-state inactivation currents with an IC50 of approximately 8 µM. Gliquidone also accelerates Kv4.3 channel inactivation and shifts the steady-state activation to a more depolarizing direction. Site-directed mutagenesis and molecular docking reveal that the residues S301 in the S4 and Y312A and L321A in the S4-S5 linker are critical for gliquidone-mediated inhibition of Kv4.3 currents, as mutating those residues to alanine significantly reduces the potency for gliquidone-mediated inhibition. Furthermore, gliquidone also inhibits a gain-of-function Kv4.3 V392I mutant identified in BrS patients in voltage- and concentration-dependent manner. Taken together, our findings demonstrate that gliquidone inhibits Kv4.3 channels by acting on the residues in the S4 and the S4-S5 linker. Therefore, gliquidone may hold repurposing potential for the therapy of Brugada syndrome. SIGNIFICANCE STATEMENT: We describe a novel role of gliquidone in inhibiting cardiac Kv4.3 currents and the channel gain-of-function mutation identified from patients with Brugada syndrome, suggesting its repurposing potential for therapy for the heart disease.

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.

A 163-bp insertion in the Capana10g000198 encoding a MYB transcription factor causes male sterility in pepper (Capsicum annuum L.).

Male sterility provides an efficient approach for commercial exploitation of heterosis. Despite more than 20 genic male sterile (GMS) mutants documented in pepper (Capsicum annuum L.), only two causal genes have been successfully identified. Here, a novel spontaneous recessive GMS mutant, designated msc-3, is identified and characterized at both phenotypic and histological levels. Pollen abortion of msc-3 mutant may be due to the delayed tapetum degradation, leading to the non-degeneration of tetrads callosic wall. Then, a modified MutMap method and molecular marker linkage analysis were employed to fine mapping the msc-3 locus, which was delimited to the ~139.91-kb region harboring 10 annotated genes. Gene expression and structure variation analyses indicate the Capana10g000198, encoding a R2R3-MYB transcription factor, is the best candidate gene for the msc-3 locus. Expression profiling analysis shows the Capana10g000198 is an anther-specific gene, and a 163-bp insertion in the Capana10g000198 is highly correlated with the male sterile (MS) phenotype. Additionally, downregulation of Capana10g000198 in male fertile plants through virus-induced gene silencing resulted in male sterility. Finally, possible regulatory relationships of the msc-3 gene with the other two reported pepper GMS genes, msc-1 and msc-2, have been studied, and comparative transcriptome analysis reveals the expression of 16 GMS homologs are significantly downregulated in the MS anthers. Overall, our results reveal that Capana10g000198 is the causal gene underlying the msc-3 locus, providing important theoretical clues and basis for further in-depth study on the regulatory mechanisms of pollen development in pepper.

Polystyrene-Based Matrix to Enhance the Fluorescence of Aggregation-Induced Emission Luminogen for Fluorescence-Guided Surgery.

Achieving ultrabright fluorogens is a key issue for fluorescence-guided surgery (FGS). Fluorogens with aggregation-induced emission (AIEgens) are potential agents for FGS on the benefit of the bright fluorescence in physiological conditions. Herein, the fluorescence brightness of AIEgen is further improved by preparing the nanoparticle using a polystyrene-based matrix and utilizing it for tumor FGS with a high signal-to-background ratio. After encapsulating AIEgen into polystyrene-poly (ethylene glycol) (PS-PEG), the fluorescence intensity of the prepared AIE@PS-PEG nanoparticles is multiple times that of nanoparticles in 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol) (DSPE-PEG), a commonly used polymer matrix for nanoparticle preparation. Molecular dynamics simulations suggest that higher free energy is required for the outer rings of AIEgen to rotate in polystyrene than in the DSPE, indicating that the benzene rings in polystyrene can restrict the intramolecular motions of AIEgen better than the alkyl chain in DSPE-PEG. Fluorescence correlation microscopy detections suggest that the triplet excited state of AIEgens is less in PS-PEG than in DSPE-PEG. The restricted intramolecular motions and suppressed triplet excited state result in ultrabright AIE@PS-PEG nanoparticles, which are more conducive to illuminating tumor tissues in the intestine for FGS. The illumination of metastatic tumors in lungs by AIE@PS-PEG nanoparticles is also tried.

Three-Dimensional Self-Supported Ge Anode for Advanced Lithium-Ion Batteries.

Three-dimensional (3D) self-supported Ge anode is one of the promising candidates to replace the traditional graphite anode material for high-performance binder-free lithium-ion batteries (LIBs). The enlarged surface area and the shortened ions/electrons transporting distance of the 3D electrode would greatly facilitate the rapid transfer of abundant lithium ions during cycling, thus achieve enhanced energy and power density during cycling. Cycle stability of the 3D self-supported Ge electrode would be improved due to the obtained enough space could effectively accommodate the large volume expansion of the Ge anode. In this review, we first describe the electrochemical properties and Li ions storage mechanism of Ge anode. Moreover, the recent advances in the 3D self-supported Ge anode architectures design are majorly illustrated and discussed. Challenges and prospects of the 3D self-supported Ge electrode are finally provided, which shed light on ways to design more reliable 3D Ge-based electrodes in energy storage systems.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy.

INTRODUCTION: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. METHODS: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). RESULTS: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. CONCLUSION: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. RESULTS: We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] µIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. CONCLUSIONS: Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.