Crosstalk of different cell-death patterns predicts prognosis and drug sensitivity in glioma.

BACKGROUND: Glioma is a malignant brain tumor originating from glial cells, and there still a challenge to accurately predict the prognosis. Programmed cell death (PCD) plays a key role in tumorigenesis and immune response. However, the crosstalk and potential role of various PCDs in prognosis and tumor microenvironment remains unknown. Therefore, we comprehensively discussed the relationship between different models of PCD and the prognosis of glioma and provided new ideas for the optimal targeted therapy of glioma. MATERIALS AND METHODS: We compared and analyzed the role of 14 PCD patterns on the prognosis from different levels. We constructed the cell death risk score (CDRS) index and conducted a comprehensive analysis of CDRS and TME characteristics, clinical characteristics, and drug response. RESULTS: Effects of different PCDs at the genomic, functional, and immune microenvironment levels were discussed. CDRS index containing 6 gene signatures and a nomogram were established. High CDRS is associated with a worse prognosis. Through transcriptome and single-cell data, we found that patients with high CDRS showed stronger immunosuppressive characteristics. Moreover, the high-CDRS group was resistant to the traditional glioma chemotherapy drug Vincristine, but more sensitive to the Temozolomide and the clinical experimental drug Bortezomib. In addition, we identified 19 key potential therapeutic targets during malignant differentiation of tumor cells. CONCLUSION: Overall, we provide the first systematic description of the role of 14 PCDs in glioma. A new CDRS model was built to predict the prognosis and to provide a new idea for the targeted therapy of glioma.

Cullin-3 proteins be a novel biomarkers and therapeutic targets for hyperchloremia induced by oral poisoning.

Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein-protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein-protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.

Exposure to Molybdate Results in Metabolic Disorder: An Integrated Study of the Urine Elementome and Serum Metabolome in Mice.

The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants are associated with the occurrence and progression of many diseases. This study exposed eight-week-old male C57 mice to sodium molybdate at doses relevant to humans (0.01 and 1 mg/kg/day) for eight weeks. Inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) were utilized to assess changes in urine element levels and serum metabolites in mice, respectively. A total of 838 subjects from the NHANES 2017-2018 population database were also included in our study to verify the associations between molybdenum and cadmium found in mice. Analysis of the metabolome in mice revealed that four metabolites in blood serum exhibited significant changes, including 5-aminolevulinic acid, glycolic acid, l-acetylcarnitine, and 2,3-dihydroxypropyl octanoate. Analysis of the elementome revealed a significant increase in urine levels of cadmium after molybdate exposure in mice. Notably, molybdenum also showed a positive correlation with cadmium in humans from the NHANES database. Further analysis identified a positive correlation between cadmium and 2,3-dihydroxypropyl octanoate in mice. In conclusion, these findings suggest that molybdate exposure disrupted amino acid and lipid metabolism, which may be partially mediated by molybdate-altered cadmium levels. The integration of elementome and metabolome data provides sensitive information on molybdate-induced metabolic disorders and associated toxicities at levels relevant to human exposure.

Ang-1 and VEGF: central regulators of angiogenesis.

Angiopoietin-1 (Ang-1) and Vascular Endothelial Growth Factor (VEGF) are central regulators of angiogenesis and are often inactivated in various cardiovascular diseases. VEGF forms complexes with ETS transcription factor family and exerts its action by downregulating multiple genes. Among the target genes of the VEGF-ETS complex, there are a significant number encoding key angiogenic regulators. Phosphorylation of the VEGF-ETS complex releases transcriptional repression on these angiogenic regulators, thereby promoting their expression. Ang-1 interacts with TEK, and this phosphorylation release can be modulated by the Ang-1-TEK signaling pathway. The Ang-1-TEK pathway participates in the transcriptional activation of VEGF genes. In summary, these elements constitute the Ang-1-TEK-VEGF signaling pathway. Additionally, Ang-1 is activated under hypoxic and inflammatory conditions, leading to an upregulation in the expression of TEK. Elevated TEK levels result in the formation of the VEGF-ETS complex, which, in turn, downregulates the expression of numerous angiogenic genes. Hence, the Ang-1-dependent transcriptional repression is indirect. Reduced expression of many target genes can lead to aberrant angiogenesis. A significant overlap exists between the target genes regulated by Ang-1-TEK-VEGF and those under the control of the Ang-1-TEK-TSP-1 signaling pathway. Mechanistically, this can be explained by the replacement of the VEGF-ETS complex with the TSP-1 transcriptional repression complex at the ETS sites on target gene promoters. Furthermore, VEGF possesses non-classical functions unrelated to ETS and DNA binding. Its supportive role in TSP-1 formation may be exerted through the VEGF-CRL5-VHL-HIF-1α-VH032-TGF-ß-TSP-1 axis. This review assesses the regulatory mechanisms of the Ang-1-TEK-VEGF signaling pathway and explores its significant overlap with the Ang-1-TEK-TSP-1 signaling pathway.

UBE2C enhances temozolomide resistance by regulating the expression of p53 to induce aerobic glycolysis in glioma.

UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

[Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats].

A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.

Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. MATERIALS AND METHODS: Dried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1ß was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. RESULTS: E. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1ß levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. CONCLUSIONS: Our results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Enhanced Plastic Stability: Achieving High Performance in a Al6xxx Alloy Fabricated by Additive Manufacturing.

Additive manufacturing (AM) facilitates the creation of materials with unique microstructural features and distinctive phenomena as compared to conventional manufacturing methods. Among the various well-fabricated AM alloys, aluminum alloys garner substantial attention due to their extensive applications in the automotive and aerospace industries. In this work, an Al6xxx alloy is successfully fabricated with outstanding performance. A nucleation agent is introduced to diminish the susceptibility to cracking during the AM process, thereby inducing a heterogeneous microstructure in this alloy. However, the introduction of ultrafine grains induces plastic instability, evidenced by the presence of Lüders band. This work investigates the evolution of the Lüders band and the strategy to reduce their undesirable effect. The heterogeneity destabilizes the band propagation and thus deteriorates the ductility. Through a T6 heat treatment, the local Lüders strain decreases from 10.0% to 6.2%, leading to a substantial enhancement in plastic stability. With the increase in grain growth and the enlargement of coarse grain regions, the mismatch between the local and macroscopic Lüders strain disappears. Importantly, the strength and the thermal conductivity are concurrently increased. The findings demonstrate the significance of ensuring plastic stability to achieve improved strength-ductility trade-off in AM alloys with heterogeneous microstructures.

Recent Advances in 4D Printing of Advanced Materials and Structures for Functional Applications.

4D printing has attracted tremendous worldwide attention during the past decade. This technology enables the shape, property, or functionality of printed structures to change with time in response to diverse external stimuli, making the original static structures alive. The revolutionary 4D-printing technology offers remarkable benefits in controlling geometric and functional reconfiguration, thereby showcasing immense potential across diverse fields, including biomedical engineering, electronics, robotics, and photonics. Here, a comprehensive review of the latest achievements in 4D printing using various types of materials and different additive manufacturing techniques is presented. The state-of-the-art strategies implemented in harnessing various 4D-printed structures are highlighted, which involve materials design, stimuli, functionalities, and applications. The machine learning approach explored for 4D printing is also discussed. Finally, the perspectives on the current challenges and future trends toward further development in 4D printing are summarized.

Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease.

Hypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD. The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six months following the 2k2c operation. Systolic blood pressure was significantly greater in the RHRSP group than in the sham-operated group at week 4 post-surgery and continued to increase over time, leading to cognitive decline by week 20. Arterial spin labeling revealed cerebral hypoperfusion in the RHRSP group at 8 weeks, accompanied by vascular remodeling and decreased vessel density. Diffusion tensor imaging and Luxol fast blue staining indicated that white matter disintegration and demyelination gradually progressed in the corpus callosum and that myelin basic protein levels decreased. Eight weeks after surgery, blood-brain barrier (BBB) leakage into the corpus callosum was observed. The albumin leakage area was negatively correlated with the myelin sheath area (r=-0.88, p<0.001). RNA-seq analysis revealed downregulation of most angiogenic genes and upregulation of antiangiogenic genes in the corpus callosum of RHRSPs 24 weeks after surgery. RHRSPs developed cerebral hypoperfusion, BBB disruption, spontaneous white matter damage, and cognitive impairment as the duration of hypertension increased. RHRSPs share behavioral and neuropathological characteristics with CSVD patients, making them suitable animal models for preclinical trials related to CSVD.

The use of Treatment and Education of Autistic and Related Communication Handicapped Children in schools to improve the ability of children with autism to complete tasks independently: A single-case meta-analysis.

OBJECTIVE: To investigate the effectiveness of a Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) intervention in schools for improving independent task performance in children with autism spectrum disorders (ASD). METHODS: We screened relevant studies published up to December 2022 from Web of science, ERIC, PsycINFO and other databases using predefined inclusion/exclusion criteria to identify suitable intervention studies for meta-analysis. Tau-U effect sizes were calculated for each A-B comparison extracted from the included experiments. Moderated analyses were conducted to examine the type of intervention (independent variable), intervention target behaviours (dependent variable), participant characteristics, setting characteristics and intervener characteristics. RESULTS: A total of 14 studies (38 participants) met the criteria and were included in the meta-analysis. The analysis results showed that TEACCH had a significant intervention effect, and the overall intervention effect size was Tau-U = 0.85[0.77, 0.91]. There were significant differences in the intervention target behaviour variables (p < 0.01), limited variation in the intervention type variables, but no differences in participant characteristics, setting characteristics and intervenor characteristics. CONCLUSION: The use of TEACCH is effective in improving independent task completion in children with ASD and provides evidence-based recommendations for its extended use in schools.

Automatic segmentation of hepatocellular carcinoma on dynamic contrast-enhanced MRI based on deep learning.

Objective. Precise hepatocellular carcinoma (HCC) detection is crucial for clinical management. While studies focus on computed tomography-based automatic algorithms, there is a rareness of research on automatic detection based on dynamic contrast enhanced (DCE) magnetic resonance imaging. This study is to develop an automatic detection and segmentation deep learning model for HCC using DCE.Approach: DCE images acquired from 2016 to 2021 were retrospectively collected. Then, 382 patients (301 male; 81 female) with 466 lesions pathologically confirmed were included and divided into an 80% training-validation set and a 20% independent test set. For external validation, 51 patients (42 male; 9 female) in another hospital from 2018 to 2021 were included. The U-net architecture was modified to accommodate multi-phasic DCE input. The model was trained with the training-validation set using five-fold cross-validation, and furtherly evaluated with the independent test set using comprehensive metrics for segmentation and detection performance. The proposed automatic segmentation model consisted of five main steps: phase registration, automatic liver region extraction using a pre-trained model, automatic HCC lesion segmentation using the multi-phasic deep learning model, ensemble of five-fold predictions, and post-processing using connected component analysis to enhance the performance to refine predictions and eliminate false positives.Main results. The proposed model achieved a mean dice similarity coefficient (DSC) of 0.81 ± 0.11, a sensitivity of 94.41 ± 15.50%, a precision of 94.19 ± 17.32%, and 0.14 ± 0.48 false positive lesions per patient in the independent test set. The model detected 88% (80/91) HCC lesions in the condition of DSC > 0.5, and the DSC per tumor was 0.80 ± 0.13. In the external set, the model detected 92% (58/62) lesions with 0.12 ± 0.33 false positives per patient, and the DSC per tumor was 0.75 ± 0.10.Significance.This study developed an automatic detection and segmentation deep learning model for HCC using DCE, which yielded promising post-processed results in accurately identifying and delineating HCC lesions.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

Hydrogen sulfide donors across time: From origins to cutting-edge applications.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.

Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.

Multifaceted Nature of HuR in Atherosclerosis Development.

HuR (Human antigen R) is an RNA binding protein (RBP) that specifically binds to certain RNA sequences, influencing post-transcriptional regulation. HuR is primarily involved in tumor regulation, as well as cell growth, proliferation, inflammation, and angiogenesis. HuR is implicated in endothelial activation, smooth muscle proliferation, inflammatory response, macrophage apoptosis, lipid regulation, and autophagy, playing a crucial regulatory role in atherosclerosis. Accumulating evidence suggests that HuR has dual roles in AS. On the one hand, HuR expedites the development of AS by facilitating endothelial activation, smooth muscle proliferation, and inflammation. On the contrary, it exerts beneficial effects by reducing macrophage apoptosis, regulating lipid efflux, and increasing autophagy. In this review, we aim to provide a comprehensive summary of the role of HuR in the development of AS by examining its involvement in cellular mechanisms, inflammation, autophagy, and apoptosis. Additionally, we discuss the mechanisms of drugs that target HuR, with the goal of offering new perspectives for the treatment of AS.

Magnetically driven formation of 3D freestanding soft bioscaffolds.

3D soft bioscaffolds have great promise in tissue engineering, biohybrid robotics, and organ-on-a-chip engineering applications. Though emerging three-dimensional (3D) printing techniques offer versatility for assembling soft biomaterials, challenges persist in overcoming the deformation or collapse of delicate 3D structures during fabrication, especially for overhanging or thin features. This study introduces a magnet-assisted fabrication strategy that uses a magnetic field to trigger shape morphing and provide remote temporary support, enabling the straightforward creation of soft bioscaffolds with overhangs and thin-walled structures in 3D. We demonstrate the versatility and effectiveness of our strategy through the fabrication of bioscaffolds that replicate the complex 3D topology of branching vascular systems. Furthermore, we engineered hydrogel-based bioscaffolds to support biohybrid soft actuators capable of walking motion triggered by cardiomyocytes. This approach opens new possibilities for shaping hydrogel materials into complex 3D morphologies, which will further empower a broad range of biomedical applications.

DNA-Nanostructure-Guided Assembly of Proteins into Programmable Shapes.

The development of methods to synthesize artificial protein complexes with precisely controlled configurations will enable diverse biological and medical applications. Using DNA to link proteins provides programmability that can be difficult to achieve with other methods. Here, we use DNA origami as an "assembler" to guide the linking of protein-DNA conjugates using a series of oligonucleotide hybridization and displacement operations. We constructed several isomeric protein nanostructures, including a dimer, two types of trimer structures, and three types of tetramer assemblies, on a DNA origami platform by using a C3-symmetric building block composed of a protein trimer modified with DNA handles. Our approach expands the scope for the precise assembly of protein-based nanostructures and will enable the formulation of functional protein complexes with stoichiometric and geometric control.

Self-Healable and 4D Printable Hydrogel for Stretchable Electronics.

Materials with high stretchability and conductivity are used to fabricate stretchable electronics. Self-healing capability and four-dimensional (4D) printability are becoming increasingly important for these materials to facilitate their recovery from damage and endow them with stimuli-response properties. However, it remains challenging to design a single material that combines these four strengths. Here, a dually crosslinked hydrogel is developed by combining a covalently crosslinked acrylic acid (AAC) network and Fe3+ ions through dynamic and reversible ionically crosslinked coordination. The remarkable electrical sensitivity (a gauge factor of 3.93 under a strain of 1500%), superior stretchability (a fracture strain up to 1700%), self-healing ability (a healing efficiency of 88% and 97% for the mechanical and electrical properties, respectively), and 4D printability of the hydrogel are demonstrated by constructing a strain sensor, a two-dimensional touch panel, and shape-morphing structures with water-responsive behavior. The hydrogel demonstrates vast potential for applications in stretchable electronics.

Rhamnose modified antibodies show improved immune killing towards EGFR-positive solid tumor cells.

Therapeutic monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) have shown clinical efficacy in colorectal cancer and other solid cancers. Enhancing the effector functions of these anti-EGFR mAbs is believed to be a valuable approach to achieve improved efficacy in clinical setting. Here, we report the development of an effector function-enhanced antibody by rhamnose (Rha) functionalization. Cetuximab, a human/mouse chimeric anti-EGFR mAb, was selected and site-specifically conjugated with Rha haptens. The obtained cetuximab-Rha conjugate was shown to be able to selectively redirect amounts of endogenous anti-Rha antibodies onto EGFR-positive solid tumor cells and thereby provide more Fc domains to achieve enhancement of effector functions including complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated phagocytosis (ADCP). Particularly, CDC, one powerful cell killing mechanism which is inactive in cetuximab, was dramatically improved. This study demonstrates the potential of rhamnose-modified antibody for EGFR-positive solid tumor immunotherapy.