Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

AIM: This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. RESULTS: Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

NSUN2 regulates Wnt signaling pathway depending on the m5C RNA modification to promote the progression of hepatocellular carcinoma.

5-Methylcytosine (m5C) RNA modification is a highly abundant and important epigenetic modification in mammals. As an important RNA m5C methyltransferase, NOP2/Sun-domain family member 2 (NSUN2)-mediated m5C RNA modification plays an important role in the regulation of the biological functions in many cancers. However, little is known about the biological role of NSUN2 in hepatocellular carcinoma (HCC). In this study, we found that the expression of NSUN2 was significantly upregulated in HCC, and the HCC patients with higher expression of NSUN2 had a poorer prognosis than those with lower expression of NSUN2. NSUN2 could affect the tumor immune regulation of HCC in several ways. In vitro and in vivo experiments confirmed that NSUN2 knockdown significantly decreased the abilities of proliferation, colony formation, migration and invasion of HCC cells. The methylated RNA immunoprecipitation-sequencing (MeRIP-seq) showed NSUN2 knockdown significantly affected the abundance, distribution, and composition of m5C RNA modification in HCC cells. Functional enrichment analyses and in vitro experiments suggested that NSUN2 could promote the HCC cells to proliferate, migrate and invade by regulating Wnt signaling pathway. SARS2 were identified via the RNA immunoprecipitation-sequencing (RIP-Seq) and MeRIP-seq as downstream target of NSUN2, which may play an important role in tumor-promoting effect of NSUN2-mediated m5C RNA modification in HCC. In conclusion, NSUN2 promotes HCC progression by regulating Wnt signaling pathway and SARS2 in an m5C-dependent manner.

The change rule of lipid oxidation and hydrolysis driven via water in Antarctic krill oil: Based on association colloid formation.

The residual water and amphiphilic compounds such as phospholipids in bulk oil can form reverse micelles, which affect oxidative stability. In this study, the Antarctic krill oil (AKO) samples with different water contents were subjected to accelerated storage. During storage, AKO exhibited oxidative changes, manifested as increased POV, TBARS values, and volatile compound levels but decreased PUFA percentages. Meanwhile, AKO underwent hydrolysis, evidenced by decreased PC, PE, and TG contents but increased FFA contents. Moreover, the degree of lipid oxidation and hydrolysis is dose-dependent with water added. Cryogenic scanning electron microscopy imaging and micelle size distribution measurement proved the presence of reverse micelle, and their size and interfacial area improved with increased water contents. Correlation analysis suggested that lipid oxidation and hydrolysis positively correlated with the size and interfacial area of reverse micelle. Therefore, it is speculated that the oil-water interface may be the site of lipid oxidation and hydrolysis.

Alteration in temporal-cerebellar effective connectivity can effectively distinguish stable and progressive mild cognitive impairment.

Background: Stable mild cognitive impairment (sMCI) and progressive mild cognitive impairment (pMCI) represent two distinct subtypes of mild cognitive impairment (MCI). Early and effective diagnosis and accurate differentiation between sMCI and pMCI are crucial for administering targeted early intervention and preventing cognitive decline. This study investigated the intrinsic dysconnectivity patterns in sMCI and pMCI based on degree centrality (DC) and effective connectivity (EC) analyses, with the goal of uncovering shared and distinct neuroimaging mechanisms between subtypes. Methods: Resting-state functional magnetic resonance imaging combined with DC analysis was used to explore the functional connectivity density in 42 patients with sMCI, 31 patients with pMCI, and 82 healthy control (HC) participants. Granger causality analysis was used to assess changes in EC based on the significant clusters found in DC. Furthermore, correlation analysis was conducted to examine the associations between altered DC/EC values and cognitive function. Receiver operating characteristic curve analysis was performed to determine the accuracy of abnormal DC and EC values in distinguishing sMCI from pMCI. Results: Compared with the HC group, both pMCI and sMCI groups exhibited increased DC in the left inferior temporal gyrus (ITG), left posterior cerebellum lobe (CPL), and right cerebellum anterior lobe (CAL), along with decreased DC in the left medial frontal gyrus. Moreover, the sMCI group displayed reduced EC from the right CAL to bilateral CPL, left superior temporal gyrus, and bilateral caudate compared with HC. pMCI demonstrated elevated EC from the right CAL to left ITG, which was linked to episodic memory and executive function. Notably, the EC from the right CAL to the right ITG effectively distinguished sMCI from pMCI, with sensitivity, specificity, and accuracy of 0.5806, 0.9512, and 0.828, respectively. Conclusion: This study uncovered shared and distinct alterations in DC and EC between sMCI and pMCI, highlighting their involvement in cognitive function. Of particular significance are the unidirectional EC disruptions from the cerebellum to the temporal lobe, which serve as a discriminating factor between sMCI and pMCI and provide a new perspective for understanding the temporal-cerebellum. These findings offer novel insights into the neural circuit mechanisms involving the temporal-cerebellum connection in MCI.

Quercetin ameliorates oxidative stress-induced apoptosis of granulosa cells in dairy cow follicular cysts by activating autophagy via the SIRT1/ROS/AMPK signaling pathway.

BACKGROUND: Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows. RESULTS: In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries. CONCLUSIONS: These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows.

Antiphospholipid syndrome presenting as recurrent coronary thrombosis: A case report.

BACKGROUND: Antiphospholipid syndrome (APS) is a chronic autoimmune disease characterized by venous or arterial thrombosis, pregnancy morbidity and a variety of other autoimmune and inflammatory complications. Here, we report a case of APS associated with multiple coronary thromboses. CASE SUMMARY: The patient, a 28-year-old male, suffered from recurrent coronary thromboses over a period of 31 months. Despite undergoing interventional coronary procedures, thrombolytic therapy, and anticoagulation treatment, the condition persisted intermittently. An extensive search for underlying thrombogenic factors revealed a diagnosis of APS. Accurate adjustment of the medication regimen led to the absence of further acute coronary syndrome (ACS) episodes during the subsequent 20-month follow-up. Although the patient occasionally experiences chest tightness, no further symptoms of distress have been reported. CONCLUSION: APS can manifest as ACS. Screening for rheumatologic and immunological conditions is essential when encountering patients with multiple coronary thromboses. Treatment strategy should include symptomatic relief and a targeted and aggressive approach to address the underlying pathophysiology.

Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.

Recent studies have established the pivotal roles of patient-derived tumour organoids (PDTOs), innovative three-dimensional (3D) culture systems, in various biological and medical applications. PDTOs, as promising tools, have been established and extensively used for drug screening, prediction of immune response and assessment of immunotherapeutic effectiveness in various cancer types, including glioma, ovarian cancer and so on. The overarching goal is to facilitate the translation of new therapeutic modalities to guide personalised immunotherapy. Notably, there has been a recent surge of interest in the co-culture of PDTOs with immune cells to investigate the dynamic interactions between tumour cells and immune microenvironment. A comprehensive and in-depth investigation is necessary to enhance our understanding of PDTOs as promising testing platforms for cancer immunotherapy. This review mainly focuses on the latest updates on the applications and challenges of PDTO-based methods in anti-cancer immune responses. We strive to provide a comprehensive understanding of the potential and prospects of PDTO-based technologies as next-generation strategies for advancing immunotherapy approaches.

Deep Learning and Habitat Radiomics for the Prediction of Glioma Pathology Using Multiparametric MRI: A Multicenter Study.

RATIONALE AND OBJECTIVES: Recent radiomics studies on predicting pathological outcomes of glioma have shown immense potential. However, the predictive ability remains suboptimal due to the tumor intrinsic heterogeneity. We aimed to achieve better pathological prediction outcomes by combining habitat analysis with deep learning. MATERIALS AND METHODS: 387 cases of primary glioma from three hospitals were collected, along with their T1 contrast-enhanced and T2-weighted MR sequences, pathological reports and clinical histories. The training set consisted of 264 patients, 82 patients composed the test set, and 41 patients were used as the validation set for hyperparameter tuning and optimal model selection. All groups were sourced from different centers. Through radiomics, deep learning, habitat analysis and combined analysis, we extracted imaging features separately and jointly modeled them with clinical features. We identified the optimal models for predicting glioma grades, Ki67 expression levels, P53 mutation and IDH1 mutation. RESULTS: Using a LightGBM model with DenseNet161 features based on habitat subregions, the best tumor grade prediction model was achieved. A LightGBM model with ResNet50 features based on habitat subregions yielded the best Ki67 expression level prediction model. An SVM model with Radiomics and Inception_v3 features provided the best prediction of P53 mutation. The best model for predicting IDH1 mutation was achieved by an MLP model with Radiomics features based on habitat subregions. Clinical features might be potentially helpful for the prediction with relatively weak evidence. CONCLUSION: Habitat+Deep Learning feature extraction methods were optimal for predicting grades and Ki67 levels. Deep Learning is optimal for predicting P53 mutation, while the combination of Habitat+ Radiomics models yielded the best prediction for IDH1 mutation.

Writers, readers, and erasers RNA modifications and drug resistance in cancer.

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing to this resistance is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing. These modifications are pivotal in regulating RNA splicing, translation, transport, degradation, and stability. Governed by "writers," "readers," and "erasers," RNA modifications impact numerous biological processes and cancer progression, including cell proliferation, stemness, autophagy, invasion, and apoptosis. Aberrant RNA modifications can lead to drug resistance and adverse outcomes in various cancers. Thus, targeting RNA modification regulators offers a promising strategy for overcoming drug resistance and enhancing treatment efficacy. This review consolidates recent research on the role of prevalent RNA modifications in cancer drug resistance, with a focus on m6A, m1A, m5C, m7G, Ψ, and A-to-I editing. Additionally, it examines the regulatory mechanisms of RNA modifications linked to drug resistance in cancer and underscores the existing limitations in this field.

Glycyrrhizic acid alleviates concanavalin A-induced acute liver injury by regulating monocyte-derived macrophages.

Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80loCD11bhiMHCIIhi MoMF-1 and decreased the abundance of pro-inflammatory F4/80loCD11bhiiNOShi MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.

van der Waals-bonded graphene clusters enhance thermal conductivity of phase-change materials for advanced thermal energy management.

Organic phase-change materials possess immense application potential, but their low thermal conductivity (≤0.5 W m-1 K-1) severely limits the thermal energy charge/discharge rate, impeding their practical implementation in the field of advanced energy. While incorporating thermally conductive fillers into the phase-change matrix can address this issue, achieving a thermal conductivity exceeding 10 W m-1 K-1 at a filler content below 30 vol% remains challenging, attributed to the absence of a well-designed filler interface and structure. Herein, a strategy for developing planar graphene clusters and subsequently integrating them with phase-change microcapsules to fabricate composites using compression molding was demonstrated. The proposed graphene clusters are formed by closely aligned and overlapping graphene sheets that bond together through van der Waals forces, resulting in a significant decrease in junction thermal resistance within the composites. Combining this interface design with compression-induced construction of a highly oriented structure, the composites achieved a remarkable thermal conductivity of 103 W m-1 K-1 with ≈29 vol% filler addition, enhancing the thermal energy charge/discharge rate by over two orders of magnitude. Furthermore, we demonstrated that the composites possess the essential enthalpy values, competent strength, and ease of shaping, making them applicable across various domains of thermal energy management.

Berberine Protects against Hepatocellular Carcinoma Progression by Regulating Intrahepatic T Cell Heterogeneity.

Accumulating evidence suggests that berberine (BBR) exhibits anti-cancer effects in hepatocellular carcinoma (HCC). However, the mechanisms by which BBR regulates the immunological microenvironment in HCC has not been fully elucidated. In this study, a mouse model of orthotopic HCC is established and treated with varying doses of BBR. BBR showed effectiveness in reducing tumor burden in mice with HCC. Cytometry by time-of-flight depicted the alterations in the tumor immune landscape following BBR treatment, revealing the enhancement in the T lymphocytes effector function. In particular, BBR decreased the proportion of TCRbhiPD-1hiCD69+CD27+ effector CD8+ T lymphocytes and increased the proportion of Ly6ChiTCRb+CD69+CD27+CD62L+ central memory CD8+ T lymphocytes. Single-cell RNA sequencing further elucidates the effects of BBR on transcriptional profiles of liver immune cells and confirms the phenotypical heterogeneity of T lymphocytes in HCC immune microenvironment. Additionally, it is found that BBR potentially regulated the antitumor immunity in HCC by modulating the receptor-ligand interaction among immune cells mediated by cytokines. In summary, the findings improve the understanding of BBR's impact on protecting against HCC, emphasizing BBR's role in regulating intrahepatic T cell heterogeneity. BBR has the potential to be a promising therapeutic strategy to hinder the advancement of HCC.

Highly oriented BN-based TIMs with high through-plane thermal conductivity and low compression modulus.

In the pursuit of effective thermal management for electronic devices, it is crucial to develop insulation thermal interface materials (TIMs) that exhibit exceptional through-plane thermal conductivity, low thermal resistance, and minimal compression modulus. Boron nitride (BN), given its outstanding thermal conduction and insulation properties, has garnered significant attention as a potential material for this purpose. However, previously reported BN-based composites have consistently demonstrated through-plane thermal conductivity below 10 W m-1 K-1 and high compression modulus, whilst also presenting challenges in terms of mass production. In this study, low molecular weight polydimethylsiloxane (PDMS) and large-size BN were utilized as the foundational materials. Utilizing a rolling-curing integrated apparatus, we successfully accomplished the continuous preparation of large-sized, high-adhesion BN films. Subsequent implementation of stacking, cold pressing, and vertical cutting techniques enabled the attainment of a remarkable BN-based TIM, characterized by an unprecedented through-plane thermal conductivity of up to 12.11 W m-1 K-1, remarkably low compression modulus (55 kPa), and total effective thermal resistance (0.16 °C in2 W-1, 50 Psi). During the TIMs performance evaluation, our TIMs demonstrated superior heat dissipation capabilities compared with commercial TIMs. At a heating power density of 40 W cm-2, the steady-state temperature of the ceramic heating element was found to be 7 °C lower than that of the commercial TIMs. This pioneering feat not only contributes valuable technical insights for the development of high-performance insulating TIMs but also establishes a solid foundation for widespread implementation in thermal management applications across a range of electronic devices.

Mechanism of discoloration of Antarctic krill oil upon storage: A study based on model systems.

The reddish-orange color of Antarctic krill oil fades during storage, and the mechanism remains unclear. Model systems containing different combinations of astaxanthin (ASTA), phosphatidylethanolamine (PE), and tocopherol were subjected to accelerated storage. Among all groups containing ASTA, only the ones with added PE showed significant fading. Meanwhile, the specific UV-visible absorption (A470 and A495) showed a similar trend. Peroxide value and thiobarbituric acid reactive substances increased during storage, while ASTA and PE contents decreased. Correlation analysis suggested that oxidized PE promoted fading by accelerating the transformation of ASTA. PE content exceeded the critical micelle concentration (1µg/g) indicating the formation of reverse micelles. Molecular docking analysis indicated that PE also interacted with ASTA in an anchor-like manner. Therefore, it is speculated that amphiphilic ASTA is more readily distributed at the oil-water interface of reverse micelles and captured by oxidized PE, which facilitates oxidation transfer, leading to ASTA oxidation and color fading.

Enhanced editing efficiency in Arabidopsis with a LbCas12a variant harboring D156R and E795L mutations.

Cas12a (Cpf1), a Class 2 Type V CRISPR/Cas nuclease, has several unique attributes for genome editing and may provide a valuable alternative to Cas9. However, a low editing efficiency due to temperature sensitivity and insufficient cleavage activity of the Cas12a nuclease are major obstacles to its broad application. In this report, we generated two variants, ttAsCas12 Ultra and ttLbCas12a Ultra harboring three (E174R, M537R, and F870L) or two (D156R and E795L) mutations, respectively, by combining the mutations from the temperature-tolerant variants ttAsCas12a (E174R) and ttLbCas12a (D156R), and those from the highly active variants AsCas12a Ultra (M537R and F870L) and LbCas12a Ultra (E795L). We compared editing efficiencies of the five resulting Cas12a variants (LbCas12a, ttLbCas12a, ttLbCas12a Ultra, AsCas12a Ultra, and ttAsCas12 Ultra) at six target sites of four genes in Arabidopsis (Arabidopsis thaliana). The variant ttLbCas12a Ultra, harboring the D156R and E795L mutations, exhibited the highest editing efficiency of all variants tested in Arabidopsis and can be used to generate homozygous or biallelic mutants in a single generation in Arabidopsis plants grown at 22 °C. In addition, optimization of ttLbCas12a Ultra, by varying nuclear localization signal sequences and codon usage, further greatly improved editing efficiency. Collectively, our results indicate that ttLbCas12a Ultra is a valuable alternative to Cas9 for editing genes or promoters in Arabidopsis. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00144-w.

PE6c greatly enhances prime editing in transgenic rice plants.

Prime editing is a versatile CRISPR/Cas-based precise genome-editing technique for crop breeding. Four new types of prime editors (PEs) named PE6a-d were recently generated using evolved and engineered reverse transcriptase (RT) variants from three different sources. In this study, we tested the editing efficiencies of four PE6 variants and two additional PE6 constructs with double-RT modules in transgenic rice (Oryza sativa) plants. PE6c, with an evolved and engineered RT variant from the yeast Tf1 retrotransposon, yielded the highest prime-editing efficiency. The average fold change in the editing efficiency of PE6c compared with PEmax exceeded 3.5 across 18 agronomically important target sites from 15 genes. We also demonstrated the feasibility of using two RT modules to improve prime-editing efficiency. Our results suggest that PE6c or its derivatives would be an excellent choice for prime editing in monocot plants. In addition, our findings have laid a foundation for prime-editing-based breeding of rice varieties with enhanced agronomically important traits.

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis.

Objective: The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Research methods and procedures: Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Results: Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Conclusion: Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. Systematic review registration: https://inplasy.com, identifier (INPLASY202440114).

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.