Graphitized Mesoporous Nanocomposites Enables Matrix-Free Soft Ionization for Multi-Class Drug Screening.

The rapid proliferation of over a thousand new psychoactive substances (NPS) presents a growing challenge for global public health and forensic science, due to their structural diversity and widespread illicit use, which significantly complicate analytical detection. In response, a fundamentally reengineered ionization strategy is introduced that integrates mesoporous graphitic-zeolite nanoparticles (MGNs) with UV-activated photothermal nanomaterials into a next-generation surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS) platform. MGNs-hierarchically structured carbon-based semiconductors synthesized via chemical vapor deposition-exhibit an exceptionally high surface area (>900 m g), broadband light absorption, and efficient photothermal energy transfer.

Neuronal NLRP3 inflammasome mediates spreading depolarization-evoked trigeminovascular activation.

Spreading depolarization (SD), the underlying mechanism of migraine aura, may trigger the opening of the pannexin 1 (PANX1) pore to sustain the cortical neuroinflammatory cascades involved in the genesis of headache. Yet, the mechanism underlying SD-evoked neuroinflammation and trigeminovascular activation remains incompletely understood. We characterized the identity of inflammasome activated following SD-evoked PANX1 opening.

NLRP12 is an innate immune checkpoint for repressing IFN signatures and attenuating lupus nephritis progression.

Signaling driven by nucleic acid sensors participates in interferonopathy-mediated autoimmune diseases. NLRP12, a pyrin-containing NLR protein, is a negative regulator of innate immune activation and type I interferon (IFN-I) production. Peripheral blood mononuclear cells (PBMCs) derived from systemic lupus erythematosus (SLE) patients expressed lower levels of NLRP12, with an inverse correlation with IFNA expression and high disease activity.

The ORF8 Protein of SARS-CoV-2 Modulates the Spike Protein and Its Implications in Viral Transmission.

COVID-19 is currently global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accompanying the rapid spread of the error-prone RNA-based genome, several dominant SARS-CoV-2 variants have been genetically identified. The mutations in the spike protein, which are essential for receptor binding and fusion, have been intensively investigated for their contributions to viral transmission.

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections.

Cell death is an essential immunological apparatus of host defense, but dysregulation of mutually inclusive cell deaths poses severe threats during microbial and parasitic infections leading to deleterious consequences in the pathological progression of infectious diseases. Nucleotide-binding oligomerization domain (NOD)-Leucine-rich repeats (LRR)-containing receptors (NLRs), also called nucleotide-binding oligomerization (NOD)-like receptors (NLRs), are major cytosolic pattern recognition receptors (PRRs), their involvement in the orchestration of innate immunity and host defense against bacteria, viruses, fungi and parasites, often results in the cleavage of gasdermin and the release of IL-1β and IL-18, should be tightly regulated. NLRs are functionally diverse and tissue-specific PRRs expressed by both immune and non-immune cells.

Reconstitution of Injectable Poly-d,l-lactic Acid: Efficacy of Different Diluents and a New Accelerating Method.

Unlabelled: Injectable poly-d,l-lactic acid (PDLLA) is a new collagen-stimulating filler containing PDLLA microspheres and carboxymethyl cellulose. It is available as a lyophilized powder that must be reconstituted with a diluent before administration. The aims of this study were to investigate the efficacy of different diluents and a new accelerating "back-and-forth" method.

Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy.

Toll-like receptors (TLRs) play crucial roles in host immune defenses. Recently, TLR-mediated autophagy is reported to promote immune responses via increasing antigen processing and presentation in antigen presenting cells. The present study examined whether the synthetic TLR4 activator (CCL-34) could induce autophagy to promote innate and adaptive immunity.

HIV-1 Tat Interacts with a Kaposi's Sarcoma-Associated Herpesvirus Reactivation-Upregulated Antiangiogenic Long Noncoding RNA, LINC00313, and Antagonizes Its Function.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), an AIDS-defining cancer with abnormal angiogenesis. The high incidence of KS in human immunodeficiency virus (HIV)-infected AIDS patients has been ascribed to an interaction between HIV type 1 (HIV-1) and KSHV, focusing on secretory proteins. The HIV-1 secreted protein HIV Tat has been found to synergize with KSHV lytic proteins to induce angiogenesis.

NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25.

Establishing the balance between positive and negative innate immune mechanisms is crucial for maintaining homeostasis. Here we uncover the regulatory crosstalk between two previously unlinked innate immune receptor families: RIG-I, an anti-viral cytosolic receptor activated type I interferon production, and NLR (nucleotide-binding domain, leucine repeat domain-containing protein). We show that NLRP12 dampens RIG-I-mediated immune signaling against RNA viruses by controlling RIG-I's association with its adaptor MAVS.

CLEC5A is a critical receptor in innate immunity against Listeria infection.

The C-type lectin member 5A (CLEC5A) is a pattern recognition receptor for members of the Flavivirus family and has critical functions in response to dengue virus and Japanese encephalitis virus. Here we show that CLEC5A is involved in neutrophil extracellular trap formation and the production of reactive oxygen species and proinflammatory cytokines in response to Listeria monocytogenes. Inoculation of Clec5a mice with L.

The collision forces and lower-extremity inter-joint coordination during running.

The purpose of this study was to compare the lower extremity inter-joint coordination of different collision forces runners during running braking phase. A dynamical system approach was used to analyse the inter-joint coordination parameters. Data were collected with six infra-red cameras and two force plates.

CLEC5A-Mediated Enhancement of the Inflammatory Response in Myeloid Cells Contributes to Influenza Virus Pathogenicity In Vivo.

Unlabelled: Human infections with influenza viruses exhibit mild to severe clinical outcomes as a result of complex virus-host interactions. Induction of inflammatory mediators via pattern recognition receptors may dictate subsequent host responses for pathogen clearance and tissue damage. We identified that human C-type lectin domain family 5 member A (CLEC5A) interacts with the hemagglutinin protein of influenza viruses expressed on lentiviral pseudoparticles through lectin screening.

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis.

Unlabelled: Osteoclasts are bone tissue macrophages critical to maintain bone homeostasis. However, whether osteoclasts are susceptible to flaviviral infections and involved in dengue virus (DV)-induced disease pathogenesis is still unknown. In this study, we found that osteoclasts were preferentially susceptible to DV infection and produced similar amounts of cytokines and infectious virions as macrophages.

Central Nervous System Melioidosis Mimics Malignancy: A Case Report and Literature Review.

Background: Central nervous system (CNS) melioidosis is notorious because of the difficulty in bacteria eradication and the destruction of brain structures. Early manifestation of CNS melioidosis mimics malignancy or stroke. We present a case of CNS melioidosis that initially manifested as malignancy.

DcR3 suppresses influenza virus-induced macrophage activation and attenuates pulmonary inflammation and lethality.

Unlabelled: Influenza A virus (IAV) infects macrophages and stimulates innate immunity receptors and sensors to produce proinflammatory cytokines and chemokines, which are responsible for IAV-induced pulmonary inflammation and injury. Decoy receptor 3 (DcR3) is a soluble protein belonging to the tumor necrosis factor receptor superfamily (TNFRSF), and is able to skew macrophage differentiation into an M2 phenotype. We demonstrated that DcR3 attenuated IAV-induced secretion of proinflammatory cytokines and chemokine from macrophages, and mitigated pulmonary infiltration and reduce lethality.

A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.

The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry.

Distinct regulation of dengue virus-induced inflammasome activation in human macrophage subsets.

Macrophages (Mϕ) are the major source of inflammatory cytokines and are target cells for dengue virus (DV) replication. However, Mϕ are heterogeneous and their phenotypic and functional diversities are influenced by cytokines that regulate their differentiation, tissue distribution, and defense against invading pathogens. In vitro, human primary macrophages are derived from peripheral blood CD14+ monocytes in the presence of macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF).

CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages.

Persistent high fever is one of the most typical clinical symptoms in dengue virus (DV)-infected patients. However, the source of endogenous pyrogen (eg, IL-1β) and the signaling cascade leading to the activation of inflammasome and caspase-1, which are essential for IL-1β and IL-18 secretion, during dengue infection have not been elucidated yet. Macrophages can be polarized into distinct phenotypes under the influence of GM-CSF or M-CSF, denoted as GM-Mϕ and M-Mϕ, respectively.

Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell.

Prostate cancer has been known to be the second highest cause of death in cancer among men. Pomegranate is rich in polyphenols with the potent antioxidant activity and inhibits cell proliferation, invasion, and promotes apoptosis in various cancer cells. This study demonstrated that pomegranate fruit juice could effectively hinder the proliferation of human prostate cancer DU145 cell.

CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality.

CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV)-induced hemorrhagic fever and shock syndrome in Stat1⁻/⁻ mice and ConA-treated wild type mice. However, whether CLEC5A is involved in the pathogenesis of viral encephalitis has not yet been investigated. To investigate the role of CLEC5A to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb and CLEC5A-deficient mice were generated.

Cytotoxic effects of celecoxib on Raji lymphoma cells correlate with aggravated endoplasmic reticulum stress but not with inhibition of cyclooxygenase-2.

Inhibition of cyclooxygenase 2 (COX-2) by the selective COX-2 inhibitor celecoxib has been suggested as potentially useful for B-cell lymphoma therapy. However, additional pharmacological activities of celecoxib have been discovered and have challenged the notion that its antitumor effects are mediated primarily via the inhibition of COX-2. To shed light on this issue, we have investigated the effects of different pharmacological agents with greatly varying COX-2 inhibitory potency in Raji lymphoma cells in vitro.

CLEC5A is critical for dengue-virus-induced lethal disease.

Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1)) contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation.