Staphylococcus aureus vesicles impair cutaneous wound healing through p38 MAPK-MerTK cleavage-mediated inhibition of macrophage efferocytosis.

Background: Staphylococcus aureus, a known contributor to non-healing wounds, releases vesicles (SAVs) that influence the delicate balance of host-pathogen interactions. Efferocytosis, a process by which macrophages clear apoptotic cells, plays a key role in successful wound healing. However, the precise impact of SAVs on wound repair and efferocytosis remains unknown.

Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.

FHIT is a fragile site tumor suppressor that is primarily inactivated upon tobacco smoking. FHIT loss is frequently observed in lung cancer, making it an important biomarker for the development of targeted therapy for lung cancer. Here, we report that inhibitors of glycogen synthase kinase 3 beta (GSK3β) and the homologous recombination DNA repair (HRR) pathway are synthetic lethal with FHIT loss in lung cancer.

[Anti-tumor therapy strategy of CAR-T cells based on stem cell memory and central memory cells].

Cancer immunotherapy including immune checkpoint inhibitors and adoptive cell therapy has gained revolutionary success in the treatment of hematologic tumors; however, it only gains limited success in solid tumors. For example, chimeric antigen receptor T (CAR-T) cell therapy has shown significant effects and potential for curing patients with B-cell malignancies. In contrast, it remains a challenge for CAR-T cell therapy to gain similar success in solid tumors.

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

Conference 2024: Building an innovative scientific research ecosystem for microbiome and One Health.

The Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals.

The interplay of factors in metabolic syndrome: understanding its roots and complexity.

Metabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes.

A Molecular Logic Gate Enables Unconventional Super-resolution Same-Day Imaging of Lysosome Membrane in Live Cells.

Lysosomes are acidic membrane-bound organelles that aid digestion, excretion, and cell renewal. The lysosomal membranes are essential for maintaining lysosomal functions and cellular homeostasis. In this work, we developed a molecular "NOR" logic gate, , by introducing malachite green into the spirocyclic rhodamine.

An electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds for repair of osteoporotic bone defects.

Repair of osteoporotic bone defects (OBD) remains a clinical challenge due to dysregulated bone homeostasis, characterized by impaired osteogenesis and excessive osteoclast activity. While drug-loaded 3D-printed scaffolds hold great potential in the restoration of bone homeostasis for enhanced OBD repair, achieving the controlled release and targeted delivery of drugs in a 3D-printed scaffold is still unmet. Herein, we developed an electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds (APS@P) with bone-targeting liposome formulation of salvianolic acid B (SAB-BTL).

Cryo-EM structures of the full-length human contactin-2.

Contactin-2 (CNTN2), an immunoglobulin cell adhesion molecule (IgCAM) expressed on the neural cell surface, regulates the formation of myelin sheaths, facilitates communication between neurons and axoglial cells, and coordinates the migration of neural cells. However, the assembly of full-length CNTN2 is still not fully elucidated. Here, we found that the full-length human CNTN2 forms a concentration-dependent homodimer.

MDSC: a new potential breakthrough in CAR-T therapy for solid tumors.

Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematologic malignancies but has encountered challenges in effectively treating solid tumors. One major obstacle is the presence of the immunosuppressive tumor microenvironment (TME), which is mainly built by myeloid-derived suppressor cells (MDSCs). Recent studies have shown that MDSCs have a detrimental effect on CAR-T cells due to their potent immunosuppressive capabilities.

New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway.

Hearing loss is caused by many factors including ototoxic drug-induced hair cell damage. Ombuoside, an antioxidant isolated from , has been suggested to serve as a new neuroprotective drug. However, the role of ombuoside in protecting inner ear hair cells from ototoxic drug-induced damage has not been investigated.

Multifaceted roles of DLG3/SAP102 in neurophysiology, neurological disorders and tumorigenesis.

DLG3, also known as Synapse-associated protein 102 (SAP102), is essential for the organization and plasticity of excitatory synapses within the central nervous system (CNS). It plays a critical role in clustering and moving key components necessary for learning and memory processes. Mutations in the DLG3 gene, which result in truncated SAP102 proteins, have been associated with a range of neurological disorders, including X-linked intellectual disability (XLID), autism spectrum disorders (ASD), and schizophrenia, all of which can disrupt synaptic structure and cognitive functions.

Uncovering the dual roles of peripheral immune cells and their connections to brain cells in stroke and post-stroke stages through single-cell sequencing.

Ischemic stroke is a cerebrovascular disease that affects the blood vessels and the blood supply to the brain, making it the second leading cause of death worldwide. Studies suggest that immune cells play a dual role during the inflammatory and recovery phases of stroke. However, in-depth investigations of specific cell subtypes and their differentiation trajectories remain to be elucidated.

TPR is required for cytoplasmic chromatin fragment formation during senescence.

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence-associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear.

Etomoxir Sodium Salt Promotes Imidazole Ketone Erastin-Induced Myeloid-Derived Suppressor Cell Ferroptosis and Enhances Cancer Therapy.

Although ferroptosis inducers trigger ferroptotic tumor cells and immune cells in the tumor microenvironment (TME), imidazole ketone erastin (IKE)'s induction of ferroptosis shows no effect on tumor growth in immunocompetent tumor-bearing mice due to the presence of myeloid-derived suppressor cells (MDSCs). Treatment of the carnitine palmitoyltransferase 1a (CPT1A)-specific inhibitor decreases the immunosuppressive function of MDSCs and enhances ferroptotic inducer-initiated tumor cell ferroptosis. However, whether blocking CPT1A could enhance IKE-induced MDSC ferroptosis and thereby inhibit tumor growth is still unclear.

In silicon desinging of RANKL-targeting vaccine for protection of osteoporosis based on the epitope of Denosumab.

Background: Life quality of osteoporosis patients is affected significantly due to the severely complications of fracture and pain. RANKL, indicated as the key mediator of osteoporosis, plays a pathogenic role of osteoclasts induction. To target this program, two medications, bisphosphonate and Denosumab, were developed and achieved remarkable advantages in clinics.

Snake venom weakens neurovascular integrity and promotes vulnerability to neuroinflammation.

Snake envenomation poses significant medical challenges, particularly in subtropical and tropical regions, with long-term impacts on neurovascular integrity and neuroinflammation remaining underexplored. This study investigates the effects of venom from four species of venomous snakes in southern China-Zhoushan Cobra (Naja atra, NA), Many-banded Krait (Bungarus multicinctus, BM), Five-paced Pit Viper (Deinagkistrodon acutus, DA), and Chinese Moccasin (Protobothrops mucrosquamatus, PM) - on the blood-brain barrier (BBB) and chronic neuroinflammation. Using mass spectrometry, we analyzed venom protein compositions, while cytotoxic effects on mouse brain endothelial cells (bEND.

Andrographolide prevents renal fibrosis via decelerating lipotoxicity-mediated premature senescence of tubular epithelial cells.

Excessive lipid accumulation often occurs in the early stage of chronic kidney disease (CKD) which is prone to induce oxidative stress and mitochondrial damage, promoting the progression of kidney fibrosis. Andrographolide (AP), a multifunctional natural terpenoids derived from Andrographis paniculate, has been suggested to play beneficial roles in metabolic disorders-associated disease. Here, we reported that AP effectively counteracts tubule injury and interstitial fibrosis in mice fed with a long-term high-fat diet (HFD).

Nuclear receptor E75/NR1D2 promotes tumor malignant transformation by integrating Hippo and Notch pathways.

Hormone therapy resistance and the ensuing aggressive tumor progression present a significant clinical challenge. However, the mechanisms underlying the induction of tumor malignancy upon inhibition of steroid hormone signaling remain poorly understood. Here, we demonstrate that Drosophila malignant epithelial tumors show a similar reduction in ecdysone signaling, the main steroid hormone pathway.

Breakthrough in cancer therapy: lutetium texaphyrin-celecoxib conjugate for immune and photodynamic treatment.

Immuno-photodynamic therapy (IPDT) has become a promising approach for cancer treatment. Innovative photosensitizers are essential to fully realize the potential of IPDT, specifically the complete elimination of tumors without recurrence. In this context, Jong Seung Kim introduce a small molecule photosensitizer conjugate, LuCXB.

Methylene Blue: An FDA-Approved NIR-II Fluorogenic Probe with Extremely Low pH Responsibility for Hyperchlorhydria Imaging.

Methylene blue (MB) is an FDA (Food and Drug Administration)-approved contrast agent with donor-acceptor (D-A) structure integrated with carbonyl-containing nitrogen-heterocycles. MB can be converted into MBH (protonated MB) by protonation, which not only induces the fluorescence emission red-shifted from the first near-infrared window (NIR-I, 650-950 nm) to the second near-infrared window (NIR-II, 1000-1700 nm) but also achieves ACQ-to-AIE conversion. MB has been successfully demonstrated in hyperacidemia imaging with an extremely low pH value (<1).

Mucus-Penetrable Biomimetic Nanoantibiotics for Pathogen-Induced Pneumonia Treatment.

Bacterial pneumonia has garnered significant attention in the realm of infectious diseases owing to a surge in the incidence of severe infections coupled with the growing scarcity of efficacious therapeutic modalities. Antibiotic treatment is still an irreplaceable method for bacterial pneumonia because of its strong bactericidal activity and good clinical efficacy. However, the mucus layer forming after a bacterial infection in the lungs has been considered as the "Achilles' heels" facing the clinical application of such treatment.

IRF3 Promotes Asthma Pathogenesis by Regulating Type 2 Innate Lymphoid Cells.

Background: Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear.