Liver macrophage-derived exosomal miRNA-342-3p promotes liver fibrosis by inhibiting HPCAL1 in stellate cells.

Background: The progression of liver fibrosis involves complex interactions between hepatic stellate cells (HSCs) and multiple immune cells in the liver, including macrophages. However, the mechanism of exosomes in the crosstalk between liver macrophages and HSCs remains unclear.

Method: Exosomes were extracted from primary mouse macrophages and cultured with HSCs, and the differential expression of microRNAs was evaluated using high-throughput sequencing technology.

Orally-administrable supramolecular probiotic capsules enable cooperative colon-targeted inflammation inhibition for ameliorating ulcerative colitis.

Ulcerative colitis (UC) is a prevalent gastrointestinal disease characterized by the chronical and refractory inflammation of colorectal mucosa and walls, which severely impairs overall well-being of individuals. Probiotics has shown tremendous promise for UC therapy due to its multifaceted mucosal barrier restoration and immunomodulation capabilities. Nevertheless, the successful administration of probiotics remains a clinical obstacle.

Optically controllable nanoregulators enable tumor-specific pro-ferroptosis lipometabolic reprogramming for in-situ adjuvant-free vaccination.

In-situ tumor vaccination remains challenging due to difficulties in the exposure and presentation of tumor-associated neoantigens (TANs). In view of the central role of lipid metabolism in cell fate determination and tumor-immune cell communication, here we report a photo-controlled lipid metabolism nanoregulator (PLMN) to achieve robust in-situ adjuvant-free vaccination, which is constructed through hierarchically integrating photothermal-inducible arachidonate 15-lipoxygenase (ALOX15)-expressing plasmids, cypate and FIN56 into cationic liposomes. Near-infrared light (NIR) stimulation triggers on-demand ALOX15 editing and causes excessive accumulation of downstream pro-ferroptosis lipid metabolites.

Erratum: Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy: Erratum.

[This corrects the article DOI: 10.7150/thno.22557.

The JNK Signaling Pathway Regulates Seizures Through ENT1 in Pilocarpine-Induced Epilepsy Rat Model.

Objective: The study investigates whether the expression and function of ENT1 can be regulated by inhibiting the JNK signaling pathway, thereby altering the levels of extracellular adenosine and glutamate in neurons, and subsequently affecting the progression of epilepsy.

Methods: The adult male SD rats were randomly divided into four groups: EP + SP600125 group, EP + DMSO group, EP group, and normal control group. The expression levels of ENT1, p-JNK, and JNK in the hippocampus of rats from each experimental group were detected using Western blotting technology.

Multifunctional layered microneedle patches enable transdermal angiogenesis and immunomodulation for scarless healing of thermal burn injuries.

Thermal burn injuries induce substantial alterations in the immune compositions and anatomical structures in the skin, which are characterized by strong inflammatory responses and thick eschar formation on the wound surface. These traits challenge current treatment paradigms due to insufficient drug penetration into affected tissues and the unsatisfactory wound regeneration. Herein, we report a layered microneedle (MN) patch for addressing these challenges in burn injury healing.

Engineered nanoplatform mediated gas therapy enhanced ferroptosis for tumor therapy .

The high glutathione (GSH) environment poses a significant challenge for inducing ferroptosis in tumor cells, necessitating the development of nanoplatforms that can deplete intracellular GSH. In this study, we developed an engineered nanoplatform (MIL-100@Era/L-Arg-HA) that enhances ferroptosis through gas therapy. First, we confirmed that the Fe element in the nanoplatform undergoes valence changes under the influence of high GSH and HO in tumor cells.

Biomaterial-Mediated Metabolic Regulation of Ferroptosis for Cancer Immunotherapy.

Ferroptosis is a lipid peroxidation-driven cell death route and has attracted enormous interest for cancer therapy. Distinct from other forms of regulated cell death, its process is involved with multiple metabolic pathways including lipids, bioenergetics, iron, and so on, which influence cancer cell ferroptosis sensitivity and communication with the immune cells in the tumor microenvironment. Development of novel technologies for harnessing the ferroptosis-associated metabolic regulatory network would profoundly improve our understanding of the immune responses and enhance the efficacy of ferroptosis-dependent immunotherapy.

Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement.

The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner.

Synthetic nanointerfacial bioengineering of Ti implants: on-demand regulation of implant-bone interactions for enhancing osseointegration.

Titanium and its alloys are the most commonly used biometals for developing orthopedic implants to treat various forms of bone fractures and defects, but their clinical performance is still challenged by the unfavorable mechanical and biological interactions at the implant-tissue interface, which substantially impede bone healing at the defects and reduce the quality of regenerated bones. Moreover, the impaired osteogenesis capacity of patients under certain pathological conditions such as diabetes and osteoporosis may further impair the osseointegration of Ti-based implants and increase the risk of treatment failure. To address these issues, various modification strategies have been developed to regulate the implant-bone interactions for improving bone growth and remodeling .

A novel coumarin-naphthalimide-based ratiometric fluorescent probe for efficiently monitoring of hydrazine in environmental water.

A novel coumarin-naphthalimide-based ratiometric fluorescent probe, called XPT, was synthesized with the aim of achieving high sensitivity and anti-interference for NH detection. The probe XPT consists of coumarin species and naphthalimide species, which act as the energy donor and acceptor, respectively. The phthalimide group functions as the recognition unit for NH.

VPS13D affects epileptic seizures by regulating mitochondrial fission and autophagy in epileptic rats.

Abnormal mitochondrial dynamics can lead to seizures, and improved mitochondrial dynamics can alleviate seizures. Vacuolar protein sorting 13D (VPS13D) is closely associated with regulating mitochondrial homeostasis and autophagy. However, further investigation is required to determine whether VPS13D affects seizures by influencing mitochondrial dynamics and autophagy.

Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells.

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1, 3)-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner.

Penfluridol regulates p62 / Keap1 / Nrf2 signaling pathway to induce ferroptosis in osteosarcoma cells.

The cure rate for patients with osteosarcoma (OS) has stagnated over the past few decades. Penfluridol, a first-generation antipsychotic, has demonstrated to prevent lung and esophageal malignancies from proliferation and metastasis. However, the effect of penfluridol on OS and its underlying molecular mechanism remains unclear.

Pathogenic genes implicated in sleep-related hypermotor epilepsy: a research progress update.

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by a variable age of onset and heterogeneous etiology. Current literature suggests a prevalence rate of approximately 1.8 per 100,000 persons.

Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies.

Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors.

The mechanism of mitochondrial autophagy regulating Clathrin-mediated endocytosis in epilepsy.

Objective: The objective of this study is to determine whether inhibition of mitophagy affects seizures through Clathrin-mediated endocytosis (CME).

Methods: Pentylenetetrazol (PTZ) was intraperitoneally injected daily to establish a chronic PTZ-kindled seizure. The Western blot (WB) was used to compare the differences in Parkin protein expression between the epilepsy group and the control group.

Pseudorabies virus usurps non-muscle myosin heavy chain IIA to dampen viral DNA recognition by cGAS for antagonism of host antiviral innate immunity.

Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated.

Mechanically Robust Hemostatic Hydrogel Membranes with Programmable Strain-Adaptive Microdomain Entanglement for Wound Treatment in Dynamic Tissues.

Supramolecular hydrogels emerge as a promising paradigm for sutureless wound management. However, their translation is still challenged by the insufficient mechanical robustness in the context of complex wounds in dynamic tissues. Herein, we report a tissue-adhesive supramolecular hydrogel membrane based on biocompatible precursors for dressing wounds in highly dynamic tissues, featuring robust mechanical resilience through programmable strain-adaptive entanglement among microdomains.

Antifungal activity and potential mechanism of action of Huangqin decoction against .

is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as in our previous drug susceptibility experiments. The antifungal activity and potential mechanism of HQD against have not yet been investigated.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy.