Application of CT and MRI images based on artificial intelligence to predict lymph node metastases in patients with oral squamous cell carcinoma: a subgroup meta-analysis.

Background: The performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC. Methods: We searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities. Results: Fourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89-0.94), 0.79 (95% CI 0.72-0.85), and 0.90 (95% CI 0.86-0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists. Discussion: In conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

Impact of pre-treatment extracellular volume fraction measured by computed tomography on response of primary lesion to preoperative chemotherapy in abdominal neuroblastoma.

OBJECTIVES: To retrospectively investigate the impact of pre-treatment Extracellular Volume Fraction (ECV) measured by Computed Tomography (CT) on the response of primary lesions to preoperative chemotherapy in abdominal neuroblastoma. METHODS: A total of seventy-five patients with abdominal neuroblastoma were retrospectively included in the study. The regions of interest for the primary lesion and aorta were determined on unenhanced and equilibrium phase CT images before treatment, and their average CT values were measured. Based on patient hematocrit and average CT values, the ECV was calculated. The correlation between ECV and the reduction in primary lesion volume was examined. A receiver operating characteristic curve was generated to assess the predictive performance of ECV for a very good partial response of the primary lesion. RESULTS: There was a negative correlation between primary lesion volume reduction and ECV (r = -0.351, p = 0.002), and primary lesions with very good partial response had lower ECV (p < 0.001). The area under the curve for ECV in predicting the very good partial response of primary lesion was 0.742 (p < 0.001), with a 95 % Confidence Interval of 0.628 to 0.836. The optimal cut-off value was 0.28, and the sensitivity and specificity were 62.07 % and 84.78 %, respectively. CONCLUSIONS: The measurement of pre-treatment ECV on CT images demonstrates a significant correlation with the response of the primary lesion to preoperative chemotherapy in abdominal neuroblastoma.

Dual-emission CPB@SMSO@SiO2 composites with tunable afterglow through energy transfer.

Afterglow materials face limitations in color variety, low luminosity, and stability. Thus, developing materials with adjustable afterglow color, increased photoluminescence (PL) intensity, and enhanced stability is crucial. This paper reports the fabrication of a series of core-shell composites, CPB@SMSO@SiO2, which combine Sr2MgSi2O7: Eu2+, Dy3+ (SMSO) and lead halide perovskite quantum dots (CsPbBr3/CPB PeQDs) through a process involving in-situ growth and hydrolytic coating. The SMSO in the composite can absorb 365 nm UV light and then emit 470 nm light, which can be absorbed by the CsPbBr3 PeQDs, resulting in an overall increase in the PL intensity of the composite. The afterglow color can be turned from green to blue by adjusting the ratio of SMSO and CsPbBr3. Furthermore, the stability of the composites is improved by the SiO2 shell layer formed by hydrolysis of tetramethyl orthosilicate (TMOS). This study presents an opportunity to develop innovative afterglow materials.

A real-world study of foreign body aspiration in children with 4227 cases in Western China.

The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P < 0.01). FBA most commonly occurs in January and February. More than 60% of FBAs occur between the ages of 1 and 2 years, and the incidence of FBA may be greater in children who are cared for by grandparents. A rigid bronchoscope can be used to remove most aspirated foreign bodies in a median of 16 min.

Comparative transcriptome provides new insights to the molecular regulation of olive trees to chilling stress.

Olive (Olea europaea. L), an economically important oil-producing crop, is sensitive to low temperature, which severely limits its productivity and geographical distribution. However, the underlying mechanism of cold tolerance in olive remains elusive. In this study, a chilling experiment (4 °C) on the living saplings of two olive cultivars revealed that O. europaea cv. Arbequina showed stronger cold tolerance with greater photosynthetic activity compared to O. europaea cv. Leccino. Transcriptome analyses revealed that early light-inducible protein 1 (ELIP1), the main regulator for chlorophyll synthesis, is dramatically induced to protect the photosynthesis at low temperatures. Furthermore, weighted gene co-expression network analysis (WGCNA), yeast one-hybrid (Y1H), and luciferase (LUC) assays demonstrated that transcription factor bHLH66 serves as an important regulator of ELIP1 transcription by binding to the G-box motif in the promoter. Taken together, our research revealed a novel transcriptional module consisting of bHLH66- ELIP1 in the adaptation of olive trees to cold stress.

Analysis of the effectiveness and safety of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis: An observational study.

This study is for exploring the effectiveness and security of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis. This retrospective study collected 100 patients with gouty arthritis between February 2022 and February 2023. According to the different treatment methods, the data of patients were divided into control group and experimental group. The control group received routine treatment with benzbromarone, while the experimental group received additional treatment with Xuedu Xiezhuo Yishen Tang on the basis of the control group. The evaluation indicators for the effectiveness of treatment include serum levels of 8-hydroxydeoxyguanosine, 3-NT, interleukin-6, interleukin-10, interleukin-1ß, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, urea nitrogen, creatinine, evaluation of knee joint function and pain level, traditional Chinese medicine syndrome score, and safety evaluation. After treatment, the overall treatment effect of the experimental group reached 98%, while the control group was 78%. After treatment, the differences in various indicators possessed statistical significance (SS) (P < .05). In the Lysholm score, the improvement in the experimental group was markedly more excellent than the control group, and the difference possessed SS (P < .05). In the NRS score, the experimental group's NRS score decreased from 8.39 to 1.08 before and after treatment, while the control group only decreased to 3.61. In addition, both groups of patients showed significant improvement in the joint score in the Traditional Chinese medicine syndrome sub-items. The experimental group was able to effectively improve symptoms such as joint pain, joint redness and swelling, joint fever, and limited joint mobility. After treatment, the incidence of adverse reactions in the experimental group was only 8%, while the incidence of adverse reactions in the control group was 24%. After statistical analysis of the incidence of adverse reactions during treatment among the participants, it was found that the difference possessed SS (P < .001). The combination treatment of Jiedu Xiezhuo Yishen Tang and benbromarone can effectively improve oxidative stress response and significantly reduce blood uric acid levels. Meanwhile, this combination therapy can effectively inhibit inflammatory reactions, significantly alleviate knee joint pain, and promote the recovery of knee joint function. This treatment regimen has lower toxic side effects and higher safety.

High-Performance Organic-Inorganic Hybrid Conductive Hydrogels for Stretchable Elastic All-Hydrogel Supercapacitors and Flexible Self-Powered Integrated Systems.

Conductive polymer hydrogels exhibit unique electrical, electrochemical, and mechanical properties, making them highly competitive electrode materials for stretchable high-capacity energy storage devices for cutting-edge wearable electronics. However, it remains extremely challenging to simultaneously achieve large mechanical stretchability, high electrical conductivity, and excellent electrochemical properties in conductive polymer hydrogels because introducing soft insulating networks for improving stretchability inevitably deteriorates the connectivity of rigid conductive domain and decreases the conductivity and electrochemical activity. This work proposes a distinct confinement self-assembly and multiple crosslinking strategy to develop a new type of organic-inorganic hybrid conductive hydrogels with biphase interpenetrating cross-linked networks. The hydrogels simultaneously exhibit high conductivity (2000 S m-1), large stretchability (200%), and high electrochemical activity, outperforming existing conductive hydrogels. The inherent mechanisms for the unparalleled comprehensive performances are thoroughly investigated. Elastic all-hydrogel supercapacitors are prepared based on the hydrogels, showing high specific capacitance (212.5 mF cm-2), excellent energy density (18.89 µWh cm-2), and large deformability. Moreover, flexible self-powered luminescent integrated systems are constructed based on the supercapacitors, which can spontaneously shine anytime and anywhere without extra power. This work provides new insights and feasible avenues for developing high-performance stretchable electrode materials and energy storage devices for wearable electronics.

Hepatitis B cure: Current situation and prospects.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1.

Glioblastoma (GBM) is the deadliest adult brain cancer. Under the current standard of care, almost all patients succumb to the disease and novel treatments are urgently needed. Recognizing that GBMs are addicted to cholesterol, past clinical trials have repurposed statins against GBM but failed. The purpose of this study was to test whether treatments that upregulate the cholesterol biosynthesis pathway in GBM would generate a metabolic vulnerability that can be exploited using statins and to determine the underlying mechanisms.Effects of radiotherapy and temozolomide or dopamine receptor antagonists on the mevalonate pathway in GBM were assessed in vitro and in vivo. The impact of statins on self-renewal of glioma stem cells and median survival was studied. Branches of the mevalonate pathway were probed to identify relevant effector proteins.Cells surviving combination treatments that converge in activating the immediate early response, universally upregulated the mevalonate pathway and increased stemness of GBM cells through activation of the Rho-GTPase Rac-1. Activation of the mevalonate pathway and Rac-1 was inhibited by statins, which led to improved survival in mouse models of glioblastoma when combined with radiation and drugs that target the glioma stem cell pool and plasticity of glioma cells.We conclude that a combination of dopamine receptor antagonists and statins could potentially improve radiotherapy outcome and warrants further investigation. SIGNIFICANCE: Combination therapies that activate the mevalonate pathway in GBM cells after sublethal treatment enhance self-renewal and migratory capacity through Rac-1 activation, which creates a metabolic vulnerability that can be further potentially exploited using statins.

Total flavonoids of Chrysanthemum indicum L inhibit colonic barrier injury induced by acute pancreatitis by affecting gut microorganisms.

BACKGROUND: Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of Chrysanthemum indicum L (TFC) have exhibited noteworthy anti-inflammatory and anti-apoptotic properties. METHODS: We established AP models, both in animals and cell cultures, employing Cerulein. 16S rRNA gene sequencing was performed to investigate the gut microorganisms changes. RESULTS: In vivo, TFC demonstrated a remarkable capacity to ameliorate AP, as indicated by the inhibition of serum amylase, myeloperoxidase (MPO) levels, and the reduction in pancreatic tissue water content. Furthermore, TFC effectively curtailed the heightened inflammatory response. The dysfunction of colonic barrier induced by AP was suppressed by TFC. At the in vitro level, TFC treatment resulted in attenuation of increased cell apoptosis, and regulation of apoptosis related proteins expression in AR42J cells. The increase of Bacteroides sartorial, Lactobacillus reuteri, Muribaculum intestinale, and Parabacteroides merdae by AP, and decrease of of Helicobacter rodentium, Pasteurellaceae bacterium, Streptococcus hyointestinalis by AP were both reversed by TFC treatment. CONCLUSIONS: TFC can effectively suppress AP progression and AP induced colonic barrier dysfunction by mitigating elevated serum amylase, MPO levels, water content in pancreatic tissue, as well as curtailing inflammation, apoptosis. The findings presented herein shed light on the potential mechanisms by which TFC inhibit the development of AP progression and AP induced colonic barrier dysfunction.

Distinguishing diffuse large B-cell lymphoma from Hodgkin's lymphoma in children using an enhanced computed tomography radiomics approach.

Background: Diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) are two completely different pathologic subtypes of lymphoma with distinctly different clinical presentations and treatment options. Thus, accurately differentiating between the two subtypes has important clinical implications. This study aimed to construct a radiomics model capable of distinguishing between DLBCL and HL based on enhanced computed tomography (CT) for the non-invasive diagnosis of lymphoma subtypes. Methods: The clinical and imaging data of 16 patients confirmed to have DLBCL (33 lymphomas), and 50 patients confirmed to have HL (106 lymphomas) were retrospectively analyzed. The patients were completely randomized into a training set (n=107, DLBLC׃HL ratio: 23׃84) and a test set (n=32, DLBCL׃HL ratio: 10׃22). After multiple down-sampling, 2,264 radiomics features were automatically extracted by the application software. Feature selection was performed in the training set using Spearman's rank correlation coefficients, maximum correlation minimum redundancy, and the least absolute shrinkage and selection operator algorithm in that order. The features after selection were used to build radiomics models by logistic regression (LR) and quadratic discriminant analysis (QDA). We evaluated the model ability using receiver operating characteristic (ROC) curves and the DeLong test. Moreover, clinical indicators, such as gender, age, clinical stage, and lactate dehydrogenase (LDH), were collected and analyzed by univariate and multivariate LR analyses. The radiomics characteristics with clinical indicators that had independent influences on predicting the pathological subtypes were used to establish a comprehensive classification model. Results: The analysis of the clinical data revealed that LDH can serve as a clinical indicator that has an independent influence on the prediction of HL and DLBCL. The results of the radiomics models were as follows: Radiomics_LR: area under the curve (AUC) =0.814 [95% confidence interval (CI): 0.628-0.999]; and Radiomics_QDA: AUC =0.841 (95% CI: 0.691-0.991). Following the inclusion of LDH as a clinical indicator in the analysis, the results of the comprehensive models were as follows: Radiomics + LDH_LR: AUC =0.768 (95% CI: 0.580-0.956); and Radiomics + LDH_QDA: AUC was 0.845 (95% CI: 0.695-0.996). Conclusions: The models based on radiomics and clinical features were able to effectively distinguish DLBCL from HL. The model with the best overall performance was the Radiomics_LR model.

A head-to-head comparison of computed tomography- and magnetic resonance imaging-based radiomics in assessing pediatric peripheral neuroblastic tumor cell behavior.

PURPOSE: To compare the performance of radiomics from contrast-enhanced computed tomography (CECT) and non-contrast magnetic resonance imaging (MRI) in assessing cellular behavior in pediatric peripheral neuroblastic tumors (PNTs). MATERIALS AND METHODS: A retrospective analysis of 81 PNT patients who underwent venous phase CECT, T1-weighted imaging (T1WI), and T2-weighted imaging (T2WI) scans was conducted. The patients were classified into neuroblastoma and ganglioneuroblastoma/ganglioneuroma based on their pathological subtypes. Additionally, they were categorized into favorable histology and unfavorable histology according to the International Neuroblastoma Pathology Classification (INPC). Tumor regions of interest were segmented on CECT, axial T1WI, and axial T2WI images, and radiomics models were developed based on the selected radiomics features. Following five-fold cross-validation, the performance of the radiomics models derived from CECT and MRI was compared using the area under the receiver operating characteristic curve (AUC) and accuracy. RESULTS: For discriminating pathological subtypes, the AUC for CECT radiomics models ranged from 0.765 to 0.870, with an accuracy range of 0.728 to 0.815. In contrast, the AUC for MRI radiomics models ranged from 0.549 to 0.748, with an accuracy range of 0.531 to 0.778. Regarding the discrimination of INPC subgroups, the AUC for CECT radiomics models ranged from 0.503 to 0.759, with an accuracy range of 0.432 to 0.741. Meanwhile, the AUC for MRI radiomics models ranged from 0.512 to 0.739, with an accuracy range of 0.605 to 0.815. CONCLUSIONS: CECT radiomics outperforms non-contrast MRI radiomics in evaluating pathological subtypes. When assessing INPC subgroups, CECT radiomics demonstrates comparability with non-contrast MRI radiomics.

The relationship between contrast-enhanced computed tomography radiomics features and mitosis karyorrhexis index in neuroblastoma.

OBJECTIVE: Mitosis karyorrhexis index (MKI) can reflect the proliferation status of neuroblastoma cells. This study aimed to investigate the contrast-enhanced computed tomography (CECT) radiomics features associated with the MKI status in neuroblastoma. MATERIALS AND METHODS: 246 neuroblastoma patients were retrospectively included and divided into three groups: low-MKI, intermediate-MKI, and high-MKI. They were randomly stratified into a training set and a testing set at a ratio of 8:2. Tumor regions of interest were delineated on arterial-phase CECT images, and radiomics features were extracted. After reducing the dimensionality of the radiomics features, a random forest algorithm was employed to establish a three-class classification model to predict MKI status. RESULTS: The classification model consisted of 5 radiomics features. The mean area under the curve (AUC) of the classification model was 0.916 (95% confidence interval (CI) 0.913-0.921) in the training set and 0.858 (95% CI 0.841-0.864) in the testing set. Specifically, the classification model achieved AUCs of 0.928 (95% CI 0.927-0.934), 0.915 (95% CI 0.912-0.919), and 0.901 (95% CI 0.900-0.909) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively, in the training set. In the testing set, the classification model achieved AUCs of 0.873 (95% CI 0.859-0.882), 0.860 (95% CI 0.852-0.872), and 0.820 (95% CI 0.813-0.839) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively. CONCLUSIONS: CECT radiomics features were found to be correlated with MKI status and are helpful for reflecting the proliferation status of neuroblastoma cells.

MACG-Net: Multi-axis cross gating network for deformable medical image registration.

Deformable Image registration is a fundamental yet vital task for preoperative planning, intraoperative information fusion, disease diagnosis and follow-ups. It solves the non-rigid deformation field to align an image pair. Latest approaches such as VoxelMorph and TransMorph compute features from a simple concatenation of moving and fixed images. However, this often leads to weak alignment. Moreover, the convolutional neural network (CNN) or the hybrid CNN-Transformer based backbones are constrained to have limited sizes of receptive field and cannot capture long range relations while full Transformer based approaches are computational expensive. In this paper, we propose a novel multi-axis cross grating network (MACG-Net) for deformable medical image registration, which combats these limitations. MACG-Net uses a dual stream multi-axis feature fusion module to capture both long-range and local context relationships from the moving and fixed images. Cross gate blocks are integrated with the dual stream backbone to consider both independent feature extractions in the moving-fixed image pair and the relationship between features from the image pair. We benchmark our method on several different datasets including 3D atlas-based brain MRI, inter-patient brain MRI and 2D cardiac MRI. The results demonstrate that the proposed method has achieved state-of-the-art performance. The source code has been released at https://github.com/Valeyards/MACG.

Correlation of cardiometabolic index and sarcopenia with cardiometabolic multimorbidity in middle-aged and older adult: a prospective study.

Background: Research has demonstrated that sarcopenia and visceral obesity are significant risk factors for chronic disease in middle-aged and older adults. However, the relationship between sarcopenia, the cardiac metabolic index (CMI), a novel measure of visceral obesity, and cardiometabolic multimorbidity (CMM) remains unclear. In this study, data from the China Longitudinal Study of Health and Retirement (CHARLS) were analyzed to investigate the association between sarcopenia and CMI with CMM in the middle-aged and older adult population. Methods: The study included 4,959 participants aged 45 and over. Sarcopenia was defined using the criteria of the Asian Sarcopenia Working Group 2019. CMM is defined as having two or more of the following conditions: physician-diagnosed heart disease, diabetes, stroke, and/or hypertension. CMI was calculated using the formula: CMI = (TG/HDL-C) × WHtR. To explore the association between CMI and sarcopenia and CMM, cox proportional risk regression models were used. Results: The median age of all participants was 57 years, with 47.1% being male. Over the 8-year follow-up, 1,362 individuals developed CMM. The incidence of CMM was 8.7/1,000 person-years in the group without sarcopenia or high CMI, 17.37/1,000 person-years in those with high CMI, 14.22/1,000 person-years in the sarcopenia group, and 22.34/1,000 person-years in the group with both conditions. After adjusting for covariates, the group with both sarcopenia and high CMI had a significantly increased risk of CMM (HR 2.48, 95% CI 1.12-5.51) and heart disease (HR 2.04, 95% CI 1.05-3.98). Among those over 65 years, sarcopenia was discovered to be associated with an increased risk of CMM [HR (95% CI: 4.83 (1.22, 19.06)]. The risk of CMM was further increased to 7.31-fold (95% CI:1.72, 31.15) when combined with high CMI. Conclusions: The combination of sarcopenia and high CMI is associated with an increased risk of developing CMM. Early identification and intervention of sarcopenia and CMI not only enable the development of targeted therapeutic strategies but also provide potential opportunities to reduce the morbidity and mortality of CMM.

Adenosine A2A Receptor Antagonist Sch58261 Improves the Cognitive Function in Alzheimer's Disease Model Mice Through Activation of Nrf2 via an Autophagy-Dependent Pathway.

Aims: Adenosine, an important endogenous neuromodulator, contributes to a broad set of several neurodegenerative diseases. The adenosine A2A receptor (A2AR) is the most involved in neuropathological effects and plays an important role in the pathogenesis of Alzheimer's disease (AD). However, the effect of A2AR antagonist and the underlying mechanism in AD model mice remains unclear. Results: The amyloid beta (Aß)1-42-induced mice AD models were used in this study. Several behavioral experiments were performed to evaluate the improvement of AD mice treated with A2AR antagonist. For mechanism analysis, autophagy-related proteins, Kelch-like ECH-associated protein1 (Keap1)-nuclear factor erythroid-derived factor 2-related factor (Nrf2) pathway activation, and synaptic function were studied using Western blot, immunofluorescence, immunohistochemistry, transmission electron microscope, real-time quantitative PCR, and patch clamp. Pharmacological blockade of adenosine A2AR by SCH58261 (SCH) ameliorated cognitive deficits and decreased expression levels of several AD biomarkers, including Aß and hyperphosphorylation of Tau. Moreover, SCH activated the Nrf2 pathway through autophagy mediated Keap1 degradation, resulting in the improvement of neuron autophagy dysfunction, synaptic plasticity, and synaptic transmission. Innovation: Our data clarified that the SCH (an antagonist of A2AR) could increase the level of autophagy, promote the ability of antioxidative stress by the activation of Keap1-Nrf2 pathway, and improve the synaptic function in Aß1-42-induced AD mice or cell model, which provided a potential therapeutic strategy for AD. Conclusion: A2AR antagonism represents a promising strategy for the anti-AD agent development through autophagy-dependent pathway.

Radiation-Induced Cellular Plasticity: A Strategy for Combatting Glioblastoma.

Glioblastoma is the deadliest brain cancer in adults and almost all patients succumb to the tumor. While surgery followed by chemo-radiotherapy significantly delays disease progression, these treatments do not lead to long-term tumor control and targeted therapies or biologics have so far failed to further improve survival. Utilizing a transient radiation-induced state of multipotency we used the adenylcyclase activator forskolin to alter the cellular fate of glioma cells in response to radiation. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation and led to a distinct gene expression profile. scRNAseq revealed that the combined treatment forced glioma cells into a microglia- and neuron-like phenotypes. In vivo this treatment led to a loss of glioma stem cells and prolonged median survival in mouse models of glioblastoma. Collectively, our data suggest that revisiting a differentiation therapy with forskolin in combination with radiation could lead to clinical benefit.

OsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice.

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.