Naringenin alleviates bone cancer pain via NF-κB/uPA/PAR2 pathway in mice.

PURPOSE: This investigation aims to explore the protective role of Naringenin (Nar) in bone cancer pain (BCP) via TNF-α-mediated NF-κB/uPA/PAR2 pathway. METHODS: BCP model was manipulated by the injection of LL2 cells into femur of mice. The levels of TNF-α and uPA in bone tissue and serum were studied by ELISA. The expressions of PAR2, PKC-γ, PKA and TRPV1 were determined by qPCR and western blot. Levels of p-IKKß, IKKß, p-p65, p65 were determined by western blot. Levels of p-p65 and uPA in bone tissue were studied by immunohistochemistry. Behavior tests in this investigation included paw withdrawal latency (PWL) and the paw withdrawal threshold (PWT). Radiological analysis and micro-CT were used to study bone structure. The lesions of bone tissue were determined by HE staining. The Dorsal root ganglia (DRG) isolated from mice were used to determine the level of PAR2 pathway. RESULTS: Naringenin improved the BCP-induced bone damage based on the increases of BV/TV, Conn. D, BMD and BMC and the decrease of bone destruction score. Naringenin repressed the reductions of PWT and PWL in BCP mice. Naringenin decreased the levels of PAR2, PKC-γ, PKA and TRPV1 of DRG and reduced the levels of p-IKKß, p-p65, and uPA in serum and bone tissue in BCP. Importantly, naringenin suppressed the enhancement of TNF-α in serum and bone tissue in BCP mice. CONCLUSION: Naringenin alleviated pain sensitization and bone damage of mice with BCP via TNF-α-mediated NF-κB/uPA/PAR2 pathway. We demonstrated a novel pathway for anti-BCP treatment with naringenin.

Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma.

Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.

Highly Stable Carboranyl Ligated Gold Nano-Catalysts for Regioselective Aromatic Bromination.

Achieving electronic/steric control and realizing selectivity regulation in nanocatalysis remains a formidable challenge, as the dynamic nature of metal-ligand interfaces, including dissolution (metal leaching) and structural reconstruction, poses significant obstacles. Herein, we disclose carboranyls (CBs) as unprecedented carbon-bonded functional ligands (Eads.CB-Au(111)=-2.90 eV) for gold nanoparticles (AuNPs), showcasing their exceptional stabilization capability that is attributed by strong Au-C bonds combined with B-H⋅⋅⋅Au interactions. The synthesized CB@AuNPs exhibit core(Aun)-satellite(CB2Au-) structure, showing high stability towards multiple stimuli (110 °C, pH=1-12, thiol etchants). In addition, different from conventional AuNP catalysts such as triphenylphosphine (PPh3) stabilized AuNPs, dissolution of catalytically active gold species was suppressed in CB@AuNPs under the reaction conditions. Leveraging these distinct features, CB@AuNPs realized outstanding p : o selectivities in aromatic bromination. Unbiased arenes including chlorobenzene (up to >30 : 1), bromobenzene (15 : 1) and phenyl acrylate were examined using CB@AuNPs as catalysts to afford highly-selective p-products. Both carboranyl ligands and carboranyl derived counterions are crucial for such regioselective transformation. This work has provided valuable insights for AuNPs in realizing diverse regioselective transformations.

Interface-Mediated Neurogenic Signaling: The Impact of Surface Geometry and Chemistry on Neural Cell Behavior for Regenerative and Brain-Machine Interfacing Applications.

Nanomaterial advancements have driven progress in central and peripheral nervous system applications such as tissue regeneration and brain-machine interfacing. Ideally, neural interfaces with native tissue shall seamlessly integrate, a process that is often mediated by the interfacial material properties. Surface topography and material chemistry are significant extracellular stimuli that can influence neural cell behavior to facilitate tissue integration and augment therapeutic outcomes. This review characterizes topographical modifications, including micropillars, microchannels, surface roughness, and porosity, implemented on regenerative scaffolding and brain-machine interfaces. Their impact on neural cell response is summarized through neurogenic outcome and mechanistic analysis. The effects of surface chemistry on neural cell signaling with common interfacing compounds like carbon-based nanomaterials, conductive polymers, and biologically inspired matrices are also reviewed. Finally, the impact of these extracellular mediated neural cues on intracellular signaling cascades is discussed to provide perspective on the manipulation of neuron and neuroglia cell microenvironments to drive therapeutic outcomes.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Challenges and advances of the stability of mRNA delivery therapeutics.

mRNA therapeutics have garnered significant attention in the biomedical realm, showing immense potential across a spectrum of applications from COVID-19 to cancer treatments. Their ability to trigger precise protein expression, particularly in genome editing, is pivotal in minimizing off-target effects. At the core of mRNA therapy lies a dual-component system, comprising the mRNA itself and a delivery vehicle. The breakthrough success of novel COVID-19 vaccines has catapulted lipid nanoparticles to prominence as the preferred delivery vehicle. However, despite their US FDA approval and efficacy, lipid nanoparticles face a significant challenge: poor stability at room temperature, which limits their applications in various geographic regions with disparities in infrastructure and technology. This review aims to dissect the issue of stability inherent in lipid nanoparticles and other mRNA delivery platforms such as polymer-based materials and protein derivative materials. We herein endeavor to unravel the factors contributing to their instability and explore potential strategies to enhance their stability. By doing so, we provide a comprehensive analysis of the current landscape of mRNA delivery systems, highlighting both their successes and limitations, and paving the way for future advancements in this rapidly evolving field.

Organs in orbit: how tissue chip technology benefits from microgravity, a perspective.

Tissue chips have become one of the most potent research tools in the biomedical field. In contrast to conventional research methods, such as 2D cell culture and animal models, tissue chips more directly represent human physiological systems. This allows researchers to study therapeutic outcomes to a high degree of similarity to actual human subjects. Additionally, as rocket technology has advanced and become more accessible, researchers are using the unique properties offered by microgravity to meet specific challenges of modeling tissues on Earth; these include large organoids with sophisticated structures and models to better study aging and disease. This perspective explores the manufacturing and research applications of microgravity tissue chip technology, specifically investigating the musculoskeletal, cardiovascular, and nervous systems.

Bioinspired multi-scale interface design for wet gas sensing based on rational water management.

Natural organisms have evolved multi-scale wet gas sensing interfaces with optimized mass transport pathways in biological fluid environments, which sheds light on developing artificial counterparts with improved wet gas sensing abilities and practical applications. Herein, we highlighted current advances in wet gas sensing taking advantage of optimized mass transport pathways endowed by multi-scale interface design. Common moisture resistance (e.g., employing moisture resistant sensing materials, post-modifying moisture resistant coatings, physical heating for moisture resistance, and self-removing hydroxyl groups) and moisture absorption (e.g., employing moisture absorption sensing materials and post-modifying moisture absorption coatings) strategies for wet gas sensing were discussed. Then, the design principles of bioinspired multi-scale wet gas sensing interfaces were provided, including macro-level condensation mediation, micro/nano-level transport pathway adjustment and molecular level moisture-proof design. Finally, perspectives on constructing bioinspired multi-scale wet gas sensing interfaces were presented, which will not only deepen our understanding of the underlying principles, but also promote practical applications.

Effect of laser phase noise on the steady-state field-mirror entanglement and ground-state cooling in a Laguerre-Gaussian optorotational system.

Cavity optomechanical systems are considered as one of the best platforms for studying macroscopic quantum phenomena. In this paper, we studied the effect of laser phase noise on the steady-state entanglement between a cavity mode and a rotating mirror in a Laguerre-Gaussian (L-G) optorotational system. We found that the effect of laser phase noise was non-negligible on the field-mirror entanglement especially at a larger input power and a larger angular momentum. We also investigated the influence of laser phase noise on the ground-state cooling of the rotating mirror. In the presence of laser phase noise, the ground-state cooling of the rotating mirror can still be realized within a range of input powers.

Enhanced Ionic Power Generation via Light-Driven Active Ion Transport Across 2D Semiconductor Heterostructures.

2D semiconductor heterostructures exhibit broad application prospects. However, regular nanochannels of heterostructures rarely caught the researcher's attention. Herein, a metal-organic framework (i.e., Cu3(HHTP)2) and transition metal dichalcogenides (i.e., MoS2)-based multilayer van der Waals heterostructure (i.e., Cu3(HHTP)2/MoS2) realized band alignment-dominated light-driven ion transport and further light-enhanced ionic energy generation. High-density channels of the heterostructure provide high-speed pathways for ion transmembrane transport. Upon light illumination, a net ionic flow occurs at a symmetric concentration, suggesting a directional cationic transport from Cu3(HHTP)2 to MoS2. This is because Cu3(HHTP)2/MoS2 heterostructures containing type-II band alignment can generate photovoltaic motive force through light-induced efficient charge separation to drive ion transport. After introducing into the ionic power generation system, the maximum power density under illumination can achieve notable improvement under different concentration differences. In addition to the photovoltaic motive force, type-II band alignment and material defect capture-induced surface charge increase also raise ion selectivity and flux, greatly facilitating ionic energy generation. This work demonstrates that 2D semiconductor heterostructures with rational band alignment can not only be a potential platform for optimizing light-enhanced ionic energy harvesting but also provide a new thought for biomimetic iontronic devices.

Zwitterion-Lubricated Hydrogel Microspheres Encapsulated with Metformin Ameliorate Age-Associated Osteoarthritis.

Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age-related osteoarthritis (OA). In the present study, highly lubricated and drug-loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)-modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti-chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA-seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO-/P53 pathway. Notably, the intra-articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age-related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

Bionic Capsule Lithium-Ion Battery Anodes for Efficiently Inhibiting Volume Expansion.

Magnetite (Fe3O4) has a large theoretical reversible capacity and rich Earth abundance, making it a promising anode material for LIBs. However, it suffers from drastic volume changes during the lithiation process, which lead to poor cycle stability and low-rate performance. Hence, there is an urgent need for a solution to address the issue of volume expansion. Taking inspiration from how glycophyte cells mitigate excessive water uptake/loss through their cell wall to preserve the structural integrity of cells, we designed Fe3O4@PMMA multi-core capsules by microemulsion polymerization as a kind of anode materials, also proposed a new evaluation method for real-time repair effect of the battery capacity. The Fe3O4@PMMA anode shows a high reversible specific capacity (858.0 mAh g-1 at 0.1 C after 300 cycles) and an excellent cycle stability (450.99 mAh g-1 at 0.5 C after 450 cycles). Furthermore, the LiNi0.8Co0.1Mn0.1O2/Fe3O4@PMMA pouch cells exhibit a stable capacity (200.6 mAh) and high-capacity retention rate (95.5 %) after 450 cycles at 0.5 C. Compared to the original battery, the capacity repair rate of this battery is as high as 93.4 %. This kind of bionic capsules provide an innovative solution for improving the electrochemical performance of Fe3O4 anodes to promote their industrial applications.

The role and therapeutic potential of macrophages in the pathogenesis of diabetic cardiomyopathy.

This review provides a comprehensive analysis of the critical role played by macrophages and their underlying mechanisms in the progression of diabetic cardiomyopathy (DCM). It begins by discussing the origins and diverse subtypes of macrophages, elucidating their spatial distribution and modes of intercellular communication, thereby emphasizing their significance in the pathogenesis of DCM. The review then delves into the intricate relationship between macrophages and the onset of DCM, particularly focusing on the epigenetic regulatory mechanisms employed by macrophages in the context of DCM condition. Additionally, the review discusses various therapeutic strategies aimed at targeting macrophages to manage DCM. It specifically highlights the potential of natural food components in alleviating diabetic microvascular complications and examines the modulatory effects of existing hypoglycemic drugs on macrophage activity. These findings, summarized in this review, not only provide fresh insights into the role of macrophages in diabetic microvascular complications but also offer valuable guidance for future therapeutic research and interventions in this field.

Synthesis of Dienamides via Palladium-catalyzed Oxidative N-α,ß-Dehydrogenation of Amides.

Enamides and their derivatives are prominent bioactive pharmacophores found in various bioactive molecules. Herein we report a palladium-catalyzed oxidative N-α,ß-dehydrogenation of amides to produce a range of enamides with high yields and excellent tolerance toward different functional groups. Mechanistic studies indicate that the reaction involves allylic C(sp3)-H activation followed by ß-H elimination. The effectiveness of this approach is demonstrated through late-stage functionalization of bioactive molecules and the synthesis of valuable compounds through product elaboration.

MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance.

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.

Changes in behavior and biomarkers during the diagnostic decision period for COVID-19, influenza, and group A streptococcus (GAS): a two-year prospective cohort study in Israel.

Background: Limited knowledge exists regarding behavioral and biomarker shifts during the period from respiratory infection exposure to testing decisions (the diagnostic decision period), a key phase affecting transmission dynamics and public health strategy development. This study aims to examine the changes in behavior and biomarkers during the diagnostic decision period for COVID-19, influenza, and group A streptococcus (GAS). Methods: We analyzed data from a two-year prospective cohort study involving 4795 participants in Israel, incorporating smartwatch data, self-reported symptoms, and medical records. Our analysis focused on three critical phases: the digital incubation period (from exposure to physiological anomalies detected by smartwatches), the symptomatic incubation period (from exposure to onset of symptoms), and the diagnostic decision period for influenza, COVID-19, and GAS. Findings: The delay between initial symptom reporting and testing was 39 [95% confidence interval (CI): 34-45] hours for influenza, 53 [95% CI: 49-58] hours for COVID-19, and 38 [95% CI: 32-46] hours for GAS, with 73 [95% CI: 67-78] hours from anomalies in heart measures to symptom onset for influenza, 23 [95% CI: 18-27] hours for COVID-19, and 62 [95% CI: 54-68] hours for GAS. Analyzing the entire course of infection of each individual, the greatest changes in heart rates were detected 67.6 [95% CI: 62.8-72.5] hours prior to testing for influenza, 64.1 [95% CI: 61.4-66.7] hours prior for COVID-19, and 58.2 [95% CI: 52.1-64.2] hours prior for GAS. In contrast, the greatest reduction in physical activities and social contacts occurred after testing. Interpretation: These findings highlight the delayed response of patients in seeking medical attention and reducing social contacts and demonstrate the transformative potential of smartwatches for identifying infection and enabling timely public health interventions. Funding: This work was supported by the European Research Council, project #949850, the Israel Science Foundation (ISF), grant No. 3409/19, within the Israel Precision Medicine Partnership program, and a Koret Foundation gift for Smart Cities and Digital Living.

In-Space Fabrication of Janus Base Nano-Matrix for Improved Assembly and Bioactivities.

In-space manufacturing of nanomaterials is a promising concept while having limited successful examples. DNA-inspired Janus base nanomaterials (JBNs), used for therapeutics delivery and tissue regeneration, are fabricated via a controlled self-assembly process in water at ambient temperature, making them highly suitable for in-space manufacturing. For the first time, we designed and accomplished the production of JBNs on orbit during the Axiom-2 (Ax-2) mission demonstrating great promising and benefits of in-space manufacturing of nanomaterials.

Identification of PPARG as key gene to link coronary atherosclerosis disease and rheumatoid arthritis via microarray data analysis.

BACKGROUND: Inflammation is the common pathogenesis of coronary atherosclerosis disease (CAD) and rheumatoid arthritis (RA). Although it is established that RA increases the risk of CAD, the underlining mechanism remained indefinite. This study seeks to explore the molecular mechanisms of RA linked CAD and identify potential target gene for early prediction of CAD in RA patients. MATERIALS AND METHODS: The study utilized five raw datasets: GSE55235, GSE55457, GSE12021 for RA patients, and GSE42148 and GSE20680 for CAD patients. Gene Set Enrichment Analysis (GSEA) was used to investigate common signaling pathways associated with RA and CAD. Then, weighted gene co-expression network analysis (WGCNA) was performed on RA and CAD training datasets to identify gene modules related to single-sample GSEA (ssGSEA) scores. Overlapping module genes and differentially expressed genes (DEGs) were considered as co-susceptible genes for both diseases. Three hub genes were screened using a protein-protein interaction (PPI) network analysis via Cytoscape plug-ins. The signaling pathways, immune infiltration, and transcription factors associated with these hub genes were analyzed to explore the underlying mechanism connecting both diseases. Immunohistochemistry and qRT-PCR were conducted to validate the expression of the key candidate gene, PPARG, in macrophages of synovial tissue and arterial walls from RA and CAD patients. RESULTS: The study found that Fc-gamma receptor-mediated endocytosis is a common signaling pathway for both RA and CAD. A total of 25 genes were screened by WGCNA and DEGs, which are involved in inflammation-related ligand-receptor interactions, cytoskeleton, and endocytosis signaling pathways. The principal component analysis(PCA) and support vector machine (SVM) and receiver-operator characteristic (ROC) analysis demonstrate that 25 DEGs can effectively distinguish RA and CAD groups from normal groups. Three hub genes TUBB2A, FKBP5, and PPARG were further identified by the Cytoscape software. Both FKBP5 and PPARG were downregulated in synovial tissue of RA and upregulated in the peripheral blood of CAD patients and differential mRNAexpreesion between normal and disease groups in both diseases were validated by qRT-PCR.Association of PPARG with monocyte was demonstrated across both training and validation datasets in CAD. PPARG expression is observed in control synovial epithelial cells and foamy macrophages of arterial walls, but was decreased in synovial epithelium of RA patients. Its expression in foamy macrophages of atherosclerotic vascular walls exhibits a positive correlation (r = 0.6276, p = 0.0002) with CD68. CONCLUSION: Our findings suggest that PPARG may serve as a potentially predictive marker for CAD in RA patients, which provides new insights into the molecular mechanism underling RA linked CAD.

The CuSCN layer between BiVO4 and NiFeOx for facilitating photogenerated carrier transfer and water oxidation kinetics.

Modification of oxygen evolution co-catalyst (OEC) on the surface of bismuth vanadate (BiVO4) can effectively improve the kinetics of water oxidation, but it is still limited by the small hole extraction driving force at the BiVO4/OEC interface. Modulating the BiVO4/OEC interface with a hole transfer layer (HTL) is expected to facilitate hole transport from BiVO4 to the OEC surface. Herein, a copper(I) thiocyanate (CuSCN) HTL is inserted between BiVO4 and NiFeOx OEC to create BiVO4/CuSCN/NiFeOx photoanode, resulting in a significant enhancement of photoelectrochemical (PEC) water splitting performance. From electrochemical analyses and density functional theory (DFT) simulations, the markedly enhanced PEC performance is attributed to the insertion of CuSCN as an HTL, which promotes the extraction of holes from BiVO4 surface and boosts the water oxidation kinetics. The optimal photoanode achieves a photocurrent density of 5.6 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) and an impressive charge separation efficiency of 96.2 %. This work offers valuable insights into the development of advanced photoanodes for solar energy conversion and emphasizes the importance of selecting an appropriate HTL to mitigate recombination at the BiVO4/OEC interface.