Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage.

Ascorbic Acid-Derived Supramolecular Gels Induce Immunogenic Ferroptosis in Cancer Cells to Potentiate Tumor Immunotherapy.

High-dose ascorbic acid (AA) therapy induces cancer cell death primarily through its oxidized derivative, dehydroascorbic acid (DHA). However, maintaining therapeutic AA concentrations within tumors and overcoming intratumoral hypoxia pose critical barriers to the clinical application of AA. Herein, we develop an injectable supramolecular gel (αPD-1@Lv/HPAGel) composed of ascorbyl palmitate (an AA derivative), lovastatin-loaded hemoglobin nanoparticles (Lv/Hb-PDA), and the immune checkpoint inhibitor anti-PD-1 (αPD-1).

Immunogenicity and safety of a recombinant gE-Fc fusion protein subunit vaccine for herpes zoster in adults ≥50 years of age: a randomised, active-controlled, non-inferiority trial.

The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly effective against herpes zoster (HZ). This randomised, active-controlled, non-inferiority trial (ChiCTR2300079076) compared the immunogenicity and safety of a novel gE-Fc fusion protein vaccine candidate (LZ901) with HZ/su in 300 healthy adults aged ≥50 years without prior HZ vaccination in Wuxi, China. Participants received either two doses of LZ901 (30-day interval; n = 151) or HZ/su (60-day interval; n = 149).

A multifunctional dihydromyricetin-loaded hydrogel for the sequential modulation of diabetic wound healing and glycemic control.

Background: The management of chronic diabetic wounds remains a formidable challenge in clinical practice. Persistent hyperglycemia triggers vasculopathy, neuropathy, and immune dysfunction, critically impeding wound repair. We developed a multifunctional hydrogel (DPFI) engineered for sequential therapeutic actions, including antibacterial, anti-inflammatory, antioxidant, pro-vascularization/epithelialization, and glycemic-regulating properties, to address these complications.

Role of in promoting radioresistance in esophageal cancer cells via the inhibition of cuproptosis.

Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related mortality worldwide, with radiotherapy (RT) being a primary treatment modality. However, radioresistance-induced tumor recurrence significantly limits the effectiveness of RT. The aim of this study is to explore potential strategies to enhance radiosensitivity and reduce the risk of local recurrence in esophageal squamous cell carcinoma.

Macrophage-mimetic liposomes co-delivering ceria and Ac2-26 peptide for penumbra protection in ischemic stroke.

Ischemic stroke is one of the most severe central nervous system disease with high disability and mortality rates worldwide. Effective treatment requires strategies that address the multifaceted pathophysiology of ischemic penumbra, including oxidative stress-induced neuronal apoptosis and blood-brain barrier (BBB) disruption. Here, inspired by the inflammation-homing property of macrophages, we developed macrophage-mimetic liposomes (MM-LPs) by integrating macrophage membranes with liposomes for the co-delivery of cerium oxide nanoparticles (CeO) and the Ac2-26 peptide (CeO-Ac2-26@MM-LPs).

Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study.

Objective: Allergic Rhinitis (AR), a prevalent allergic condition, markedly diminishes quality of life and increases public health burdens. This study investigated the mediating roles of Metabolic Biomarkers (MBs) in the associations between Circulating Inflammatory Proteins (CIPs) and AR, aiming to uncover novel therapeutic targets.

Methods: Utilizing Mendelian Randomization (MR), we leveraged genetic variants as instrumental variables to delineate causal relationships between CIPs and AR.

[Performance evaluation of a wearable steady-state visual evoked potential based brain-computer interface in real-life scenario].

Brain-computer interface (BCI) has high application value in the field of healthcare. However, in practical clinical applications, convenience and system performance should be considered in the use of BCI. Wearable BCIs are generally with high convenience, but their performance in real-life scenario needs to be evaluated.

USP49 undergoes liquid-liquid phase separation and stabilizes RPA70 to induce radioresistance through homologous recombination repair in esophageal squamous cell carcinoma.

Radiotherapy is crucial in the comprehensive management of esophageal squamous cell carcinoma (ESCC). Nevertheless, its efficacy is compromised by the emergence of radioresistance, leading to poor prognoses. Accumulating research has underscored the critical role of deubiquitinases (DUBs) in modulating radiosensitivity.

The novel compound CP-10 suppresses microglia-mediated neuroinflammation and neutrophil chemotaxis and attenuates ischemic brain injury by targeting FPR1.

Ischemic stroke represents a major neurological disorder characterized by significant morbidity, where neuroinflammation plays a central role in exacerbating cerebral injury. Following ischemic events, microglial activation and the subsequent infiltration of peripheral immune cells, particularly neutrophils, contribute to the disruption of the blood-brain barrier and amplify neuronal damage. In the present study, as a part of our ongoing screening experiment to evaluate the anti-inflammatory effects of new compounds, a novel compound, namely N-{2-[(7-chloro-4-oxo-4H-pyrido[1,2-a] pyrimidin-2-yl) methoxy] phenyl}-2,2-dimethylpropanamide (referred to as CP-10 in this study), to test whether it could target microglial activation and neutrophil chemotaxis, both critical contributors to ischemic brain injury.

Discovery of 2-Amino-7-Amide Quinazoline Derivatives as Potent and Orally Bioavailable Inhibitors Targeting Extracellular Signal-Regulated Kinase 1/2.

Aberrant activation of the ERK/MAPK pathway is closely associated with various cancers. Directly targeting ERK1/2, the most distal node of this cascade, is not only a rational therapeutic approach for cancers harboring pathway-activating alterations, but also provides a potential solution for overcoming resistance from upstream signaling. Herein, we described the discovery of potent and orally bioavailable ERK1/2 inhibitors featuring 2-amino-7-amide quinazoline skeletons through structure-based drug design.

Screening of key active ingredients of Fuyuan Shenghua granules for the treatment of medical abortion using ingredient-target interaction and pharmacokinetics.

Fuyuan Shenghua granule (FYSHG) is a clinical herbal formula adapted for medical abortion as an adjuvant treatment. This study aimed to screen the key active ingredients of FYSHG in treating medical abortion in vivo using ingredient-protein interaction and pharmacokinetics. The main ingredients of FYSHG absorbed in the blood were identified through UHPLC-Q-TOF/MS.

Shionone protects cerebral ischemic injury through alleviating microglia-mediated neuroinflammation.

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury.

Lactic Acid Metabolism-Related Gene May Act as a Prognostic Predictor by FARS2 in Nasopharyngeal Carcinoma.

BackgroundThis study aimed to investigate the clinical value of lactic acid metabolism-related genes (LRGs) in nasopharyngeal carcinoma (NPC).MethodsClinical and genetic information was extracted from the TGCA and Gene Expression Omnibus databases. Consistency clustering was employed to identify NPC subpopulations.

Differential analysis of milk fatty acids in human, Saanen dairy goat, Chinese Holstein cow, and Jersey cow milk at different stages of lactation.

Objective: The objective of this study was to investigate the differences in fatty acid composition of human breast milk from Holstein cows, Jersey cows, Saanen goats, and humans at different lactation period and to find possible substitute milk for breast milk.

Methods: In this study, human breast milk, Saanen milk, Holstein milk, and Jersey milk were collected at different lactation stages. Gas chromatography (GC-MS) was used to determine the fatty acid composition of breast milk, Saanen milk, goat's milk, Holstein cow's milk and Jersey cows at different stages of lactation.

Metabolic Biomarkers Mediate Allergic Conjunctivitis via Circulating Inflammatory Proteins: Evidence From a Mendelian Randomization Study.

Purpose: This study aimed to investigate the mediating role of metabolic biomarkers (MBs) in the association between circulating inflammatory proteins (CIPs) and allergic conjunctivitis (AC) and identify potential therapeutic targets.

Methods: A Mendelian randomization (MR) study was conducted, leveraging genetic variants as instrumental variables to infer causal relationships. Data were obtained from genome-wide association studies (GWASs), and a two-sample MR was employed to estimate the direct and indirect effects of CIPs on AC through MBs.

Exploring causal relationships between circulating micronutrients and age-related eye diseases: a Mendelian randomization study.

Background: With the global population aging, age-related eye diseases (AREDs) such as senile cataract (SC), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are becoming increasingly significant public health concerns. The rising prevalence of AREDs underscores the urgent need for effective prevention and treatment strategies. This study aimed to explore the causal relationships between circulating micronutrients (CMs) and AREDs.

A Light-Driven Electrochromic Materials-Based Nanomotor for HS-Controlled Drug Release in Synergistic Cancer Chemotherapy Immunotherapy.

Nanomotors hold tremendous potential for drug delivery. However, current nanomotors face limitations that compromise efficiency of drug utilization, including the use of inorganic materials with suboptimal soft interface and biocompatibility, uncontrollable drug release, insufficient directional control, and slow movement speeds. Herein, we present a novel near-infrared (NIR) light-driven porous unsymmetric nanomotor with ultrafast motion, which utilizes hydrogen sulfide (HS)-responsive cationic organic π-electron structure-based electrochromic material (F1) for the payload and controlled release of anionic anticancer drugs, enabling synergistic cancer chemotherapy and immunotherapy.

Ratiometric Photoacoustic Imaging Probe for Self-Predicting Nanozyme Therapeutic Effects.

Nanozymes with intrinsic enzyme-like properties have garnered significant attention in cancer treatment. However, effective methods to evaluate in situ the catalytic activity of nanozymes in living systems remain lacking. Herein, we pioneeringly present a novel probe (-FCuSA) for self-reporting nanozyme catalytic activity, which integrates a diene electrochromic material (EM ) and a copper single-atom nanozyme (FCuSA) with peroxidase (POD)-like activity.

Baicalin loaded monodispersed polycaprolactone (PCL) microspheres preparation by polyvinylidene fluoride (PVDF) membrane emulsification for wound healing in dermal fibroblasts.

The development of injectable bio-stimulating polycaprolactone (PCL) microspheres for wound healing has strict requirement on size and morphology control, particularly favoring microspheres within the range between 20-50 µm. PCL microspheres with smaller sizes are phagocyted at rapid rate while larger microspheres could cause inflammation. Homogenization can be regarded as an irreversible process to generate microspheres of particular size range while it still remains as the most common approach for microspheres production.

Dual-Locked Near-Infrared Fluorescent Probe for Real-Time Imaging of Hydrogen Sulfide/Matrix Metallopeptidase-2 In Vivo.

Hydrogen sulfide (HS) and matrix metallopeptidase 2 (MMP-2) are inextricably linked in the occurrence and development of diseases and the treatment of diseases. However, most of the activatable imaging probes currently developed are single-locked probes that do not simultaneously detect HS and MMP-2 levels at disease sites and severely hinder the real-time and accurate analysis of the dynamic relationship between the two interrelated biomarkers. Herein, we report a dual-locked HS/MMP-2-activatable near-infrared (NIR) fluorescent imaging probe through a dual-Förster resonance energy transfer (FRET) mechanism that specifically detects tumors or acute lung injury (ALI) and establishes the dynamic relationship between the HS level and MMP-2 expression.

Follicular fluid and plasma lipidome profiling and associations towards embryonic development outcomes during ART treatment.

Introduction: It is well acknowledged that lipids assume a critical role in oocyte maturation and early embryonic metabolism, this study aimed to evaluate the relationship between the lipid composition of plasma and follicular fluid (FF), and the consequences of embryonic development. This study compared the lipidomic profiles of paired plasma and FF samples obtained from sixty-five Chinese women who underwent assisted reproductive technology (ART) treatments.

Methods: Non-targeted lipidomics analysis.

NG-497 Alleviates Microglia-Mediated Neuroinflammation in a MTNR1A-Dependent Manner.

Microglia-mediated neuroinflammation plays a crucial role in multiple neurological diseases. We have previously found that Atglistatin, the mouse Adipose Triglyceride Lipase (ATGL) inhibitor, could promote lipid droplets (LDs) accumulation and suppress LPS-induced neuroinflammation in mouse microglia. However, Atglistatin was species-selective, which limited its use in clinical settings.

CircINADL promotes nasopharyngeal carcinoma metastasis by inhibiting HuR ubiquitin degradation and disrupting the hippo signaling pathway.

Distant metastasis is a primary factor contributing to the low survival rate of patients with nasopharyngeal carcinoma (NPC). Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer initiation and progression. However, the mechanisms underlying the abnormal expression and biological function of circRNA in NPC remain unclear.