Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters.

Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans.

Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region.

Amyloid-β (Aβ) deposition throughout the neuroaxis is a classical hallmark of several neurodegenerative diseases, most notably Alzheimer's disease (AD). Aβ peptides of varied length and diverse structural conformations are deposited within the parenchyma and vasculature in the brains of individuals with AD. Neuropathologically, Aβ pathology can be assessed using antibodies to label and characterize their features, which in turn leads to a more extensive understanding of the pathological process.

Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome.

Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade.

There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due to dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment and activation.

S100A4 Is a Key Facilitator of Thoracic Aortic Dissection.

Thoracic aortic dissection (TAD) is one of the cardiovascular diseases with high incidence and fatality rates. Vascular smooth muscle cells (VSMCs) play a vital role in TAD formation. Recent studies have shown that extracellular S100A4 may participate in VSMCs regulation.

Aβ Amyloid Scaffolds the Accumulation of Matrisome and Additional Proteins in Alzheimer's Disease.

We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein changes observed in the CRND8 mice with co-expression networks derived from human AD, reveals both conserved and divergent module changes. For the most highly conserved module (M42, matrisome) we find many proteins accumulate in plaques, cerebrovascular amyloid (CAA), dystrophic processes, or a combination thereof.

A C1qTNF3 collagen domain fusion chaperones diverse secreted proteins and anti-Aβ scFvs: Applications for gene therapies.

Enhancing production of protein cargoes delivered by gene therapies can improve efficacy by reducing the amount of vector or simply increasing transgene expression levels. We explored the utility of a 126-amino acid collagen domain (CD) derived from the C1qTNF3 protein as a fusion partner to chaperone secreted proteins, extracellular "decoy receptor" domains, and single-chain variable fragments (scFvs). Fusions to the CD domain result in multimerization and enhanced levels of secretion of numerous fusion proteins while maintaining functionality.

CXCL9 recombinant adeno-associated virus (AAV) virotherapy sensitizes glioblastoma (GBM) to anti-PD-1 immune checkpoint blockade.

The promise of immunotherapy to induce long-term durable responses in conventionally treatment resistant tumors like glioblastoma (GBM) has given hope for patients with a dismal prognosis. Yet, few patients have demonstrated a significant survival benefit despite multiple clinical trials designed to invigorate immune recognition and tumor eradication. Insights gathered over the last two decades have revealed numerous mechanisms by which glioma cells resist conventional therapy and evade immunological detection, underscoring the need for strategic combinatorial treatments as necessary to achieve appreciable therapeutic effects.

Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of clinically aggressive tumors with high risk of recurrence and metastasis. Current pharmacological treatment options remain largely limited to chemotherapy. Despite promising results, the efficacy of immunotherapy and chemo-immunotherapy in TNBC remains limited.

Ebola virus VP35 perturbs type I interferon signaling to facilitate viral replication.

As one of the deadliest viruses, Ebola virus (EBOV) causes lethal hemorrhagic fevers in humans and nonhuman primates. The suppression of innate immunity leads to robust systemic virus replication of EBOV, leading to enhanced transmission. However, the mechanism of EBOV-host interaction is not fully understood.

Effects of sedimentary organic matter degradation and structure on nonylphenol degradation by sodium persulfate.

The structure and constituents of sedimentary organic matter (SOM) in the degradation of benzene ring-C labeled 4-nonylphenol (C-NP) by sodium persulfate (NaSO) were investigated. NaSO mineralized over 84 % of C-NP to CO, and no parent unlabeled 4-nonylphenol (NP) compounds were detected in the water-soluble/supernatant phase or extractable residues. Organic carbon (OC) was sequentially separated from six sediment samples collected from the Pearl River (BET), estuary (GSD), continental shelf (S11 and S21), and deep sea (M9 and M10).

Effect of organic carbon structures on the degradation of nonylphenol by hydrogen peroxide in sediment-water system.

A laboratory experiment is conducted to investigate the effects of organic carbon (OC) from riverine and marine sediments on the degradation of ring- C-labeled nonylphenol ( C-NP) by hydrogen peroxide (H O ). Researchers have isolated demineralized OC (DM) before and after oxidation, namely, DM and resistant OC (ROC) fractions, respectively. The structures of DM and ROC are characterized using solid-state C nuclear magnetic resonance.

African Swine Fever Virus Cysteine Protease pS273R Inhibits Type I Interferon Signaling by Mediating STAT2 Degradation.

African swine fever virus (ASFV) is a large DNA virus that causes African swine fever (ASF), an acute and hemorrhagic disease in pigs with lethality rates of up to 100%. To date, how ASFV efficiently suppress the innate immune response remains enigmatic. In this study, we identified ASFV cysteine protease pS273R as an antagonist of type I interferon (IFN).

Role of the sedimentary organic matter structure and microporosity on the degradation of nonylphenol by potassium ferrate.

In this study, the role of organic matter structure and microporosity in the adsorption and degradation of radioactive nonylphenol in sediments treated with potassium ferrate solutions was investigated. The demineralized fractions and acid non-hydrolyzable fractions were isolated and characterized via advanced solid-state C nuclear magnetic resonance and CO gas adsorption technology, respectively. Radioactive nonylphenol in the sediments was also fractionated into CO, water-soluble residues, extractable residues, and strongly bound residues after treatment with potassium ferrate.

Analysis of the Reform Effectiveness of Vocational Skill Identification Based on the New Social Training Model in the New Era under Deep Learning Assessment.

In order to be able to make full use of domain knowledge to improve the performance of skill word extraction, this paper proposes a skill word extraction method based on a combination of deep learning and corpus features. Skill word extraction is transformed into a sequence annotation problem, and based on the basic model of sequence annotation, Bi-LSTM-CRF, corpus features are added to the input layer, and the output of the input layer is connected with the Bi-LSTM output as the input of the CRF layer. The experimental results show timely updating of the question bank, paying attention to the quality of vocational skill identification, and strictly managing the issuance of vocational qualification false certificates.

African swine fever virus I267L acts as an important virulence factor by inhibiting RNA polymerase III-RIG-I-mediated innate immunity.

ASFV is a large DNA virus that is highly pathogenic in domestic pigs. How this virus is sensed by the innate immune system as well as why it is so virulent remains enigmatic. In this study, we show that the ASFV genome contains AT-rich regions that are recognized by the DNA-directed RNA polymerase III (Pol-III), leading to viral RNA sensor RIG-I-mediated innate immune responses.

FAM177A1 Inhibits IL-1β-Induced Signaling by Impairing TRAF6-Ubc13 Association.

The proinflammatory cytokine IL-1β is a crucial mediator of inflammatory responses. IL-1β-induced signaling is finely regulated by various mechanisms, and its imbalance is involved in a variety of diseases. In this study, we identified FAM177A1, a protein of unknown function, as a negative regulator of IL-1β-induced signaling in human cells.

Switch-associated protein 70 protects against nonalcoholic fatty liver disease through suppression of TAK1.

Background And Aims: NAFLD is a progressive disease without known effective drug treatments. Switch-associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear.

African swine fever virus protein MGF-505-7R promotes virulence and pathogenesis by inhibiting JAK1- and JAK2-mediated signaling.

African swine fever virus (ASFV) is a large DNA virus that is highly contagious and pathogenic in domestic pigs with a mortality rate up to 100%. However, how ASFV suppresses JAK-STAT1 signaling to evade the immune response remains unclear. In this study, we found that the ASFV-encoded protein MGF-505-7R inhibited proinflammatory IFN-γ-mediated JAK-STAT1 signaling.

Effect of the structure and micropore of activated and oxidized black carbon on the sorption and desorption of nonylphenol.

Activated, oxidized, and solvent-extracted black carbon samples (BCs) were produced from a shale kerogen at temperatures ranging from 250 to 500 °C by chemical activation regents (KOH, ZnCl), oxidative regents (HO, NaClO), and organic solvents, respectively. Extracted organic matter (EOM) and polycyclic aromatic hydrocarbons (PAHs) were quantified in BCs, and they increased and then decreased with increasing temperature. Sorption and desorption isotherms of nonylphenol (NP) on BCs were compared with those previously reported for phenanthrene (Phen).

Ubiquitination of TLR3 by TRIM3 signals its ESCRT-mediated trafficking to the endolysosomes for innate antiviral response.

Trafficking of toll-like receptor 3 (TLR3) from the endoplasmic reticulum (ER) to endolysosomes and its subsequent proteolytic cleavage are required for it to sense viral double-stranded RNA (dsRNA) and trigger antiviral response, yet the underlying mechanisms remain enigmatic. We show that the E3 ubiquitin ligase TRIM3 is mainly located in the Golgi apparatus and transported to the early endosomes upon stimulation with the dsRNA analog poly(I:C). TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831, which is enhanced following poly(I:C) stimulation.

Impact of trophic levels on partitioning and bioaccumulation of polycyclic aromatic hydrocarbons in particulate organic matter and plankton.

The distribution and bioconcentration of polycyclic aromatic hydrocarbons (PAHs) in water, suspended particulate material (SPM), algae, and zooplankton samples from the Pearl River Delta (PRD), South China, were investigated. The PAHs in the water and SPM samples is significantly associated with chlorophyll a (Chl a), implying the important role of the aquatic productivity on PAH distribution. PAHs in the water or SPM samples were strongly correlated to dissolved organic carbon (DOC) or algal particulate organic carbon (A-POC).

CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.

Notch signaling provides an important cue in the mammalian developmental process. It is a key player in T cell development and function. Notch ligands such as Delta-like ligands (DLL) 1, 3, 4, and JAG1, 2 can impact Notch signaling positively or negatively, by -activation or -inhibition.

γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not.

Background: γ-Secretase is a multiprotein protease that cleaves amyloid protein precursor (APP) and other type I transmembrane proteins. It has two catalytic subunits, presenilins 1 and 2 (PS1 and 2). In our previous report, we observed subtle differences in PS1- and PS2-mediated cleavages of select substrates and slightly different potencies of PS1 versus PS2 inhibition for select γ-secretase inhibitors (GSIs) on various substrates.