Targeting LRRC41 as a potential therapeutic approach for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, characterized by high mortality rate. In clinical practice, several makers of liver cancer, such as VEGFR1, FGFR1 and PDGFRα, were identified and their potentials as a therapeutic target were explored. However, the unsatisfied treatment results emphasized the needs of new therapeutic targets.

Successful clearance of persistent SARS-CoV-2 asymptomatic infection following a single dose of Ad5-nCoV vaccine.

Persistent asymptomatic (PA) SARS-CoV-2 infections have been identified. The immune responses in these patients are unclear, and the development of effective treatments for these patients is needed. Here, we report a cohort of 23 PA cases carrying viral RNA for up to 191 days.

Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2.

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV.

Pharmacological inhibition of Carbonic Anhydrase IX and XII to enhance targeting of acute myeloid leukaemia cells under hypoxic conditions.

Acute myeloid leukaemia (AML) is an aggressive form of blood cancer that carries a dismal prognosis. Several studies suggest that the poor outcome is due to a small fraction of leukaemic cells that elude treatment and survive in specialised, oxygen (O )-deprived niches of the bone marrow. Although several AML drug targets such as FLT3, IDH1/2 and CD33 have been established in recent years, survival rates remain unsatisfactory, which indicates that other, yet unrecognized, mechanisms influence the ability of AML cells to escape cell death and to proliferate in hypoxic environments.

Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients.

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies.

Remarkable untangled dynamics behavior of multicyclic branched polystyrenes.

A typical multicyclic branched-topology polystyrene (c-BPS) with high molecular weight (30 K ≤ Mw MALLS ≤ 300 K g mol-1) and narrow dispersity (1.2 ≤ Đ ≤ 1.3) was efficiently synthesized by combining atom transfer radical polymerization (ATRP) and atom transfer radical coupling (ATRC) techniques.

Classic and targeted anti-leukaemic agents interfere with the cholesterol biogenesis metagene in acute myeloid leukaemia: Therapeutic implications.

Despite significant advances in deciphering the molecular landscape of acute myeloid leukaemia (AML), therapeutic outcomes of this haematological malignancy have only modestly improved over the past decades. Drug resistance and disease recurrence almost invariably occur, highlighting the need for a deeper understanding of these processes. While low O compartments, such as bone marrow (BM) niches, are well-recognized hosts of drug-resistant leukaemic cells, standard in vitro studies are routinely performed under supra-physiologic (21% O , ambient air) conditions, which limits clinical translatability.

In Vitro Antibacterial Activities and Mechanisms of Action of Fatty Acid Monoglycerides Against Four Foodborne Bacteria.

Abstract: Naturally occurring monoglyceride esters of fatty acids have been associated with a broad spectrum of antimicrobial activities. We used an automated turbidimetric method to measure the MIC and assess the antimicrobial activity of five monoglycerides (monocaprin, monolaurin, monomyristin, monopalmitin, and monostearin) against pathogenic strains of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli. The antibacterial activity of monocaprin was highest because its carbon chain is shorter than those of other monoglycerides.

Highly Selective Synthesis of Monolaurin via Enzymatic Transesterification under Batch and Continuous Flow Conditions.

This study aimed to investigate the highly selective production of monolaurin via enzymatic transesterification of methyl laurate and glycerol. It was determined that a binary solvent system (tert-butanol/iso-propanol, 20:80, wt./wt.

Stabilization of enzyme-immobilized hydrogels for extended hypoxic cell culture.

In this work, glucose oxidase (GOx)-immobilized hydrogels are developed and optimized as an easy and convenient means for creating solution hypoxia in a regular incubator. Specifically, acrylated GOx co-polymerizes with poly(ethylene glycol) diacrylate (PEGDA) to form PEGDA-GOx hydrogels. Results show that freeze-drying and reaction by-products, hydrogen peroxide, negatively affect oxygen-consuming activity of network-immobilized GOx.

Top-Down Suppression of Sensory Cortex in an NMDAR Hypofunction Model of Psychosis.

Conceptual and computational models have been advanced that propose that perceptual disturbances in psychosis, such as hallucinations, may arise due to a disruption in the balance between bottom-up (ie sensory) and top-down (ie from higher brain areas) information streams in sensory cortex. However, the neural activity underlying this hypothesized alteration remains largely unexplored. Pharmacological N-methyl-d-aspartate receptor (NMDAR) antagonism presents an attractive model to examine potential changes as it acutely recapitulates many of the symptoms of schizophrenia including hallucinations, and NMDAR hypofunction is strongly implicated in the pathogenesis of schizophrenia as evidenced by large-scale genetic studies.

A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells with mutations.

An activating mutation of () is the most frequent genetic alteration associated with poor prognosis in acute myeloid leukemia (AML). Although many FLT3 inhibitors have been clinically developed, no first-generation inhibitors have demonstrated clinical efficacy by monotherapy, due to poor pharmacokinetics or unfavorable safety profiles possibly associated with low selectivity against FLT3 kinase. Recently, a selective FLT3 inhibitor, quizartinib, demonstrated favorable outcomes in clinical studies.

Neural crest cell-specific inactivation of Nipbl or Mau2 during mouse development results in a late onset of craniofacial defects.

Nipbl (Scc2) and Mau2 (Scc4) encode evolutionary conserved proteins that play a vital role for loading the cohesin complex onto chromosomes, thereby ensuring accurate chromosome segregation during cell division. While mutations in human NIPBL are known to cause the developmental disorder Cornelia de Lange syndrome, the functions of Nipbl and Mau2 in mammalian development are poorly defined. Here we generated conditional alleles for both genes in mice and show that neural crest cell-specific inactivation of Nipbl or Mau2 strongly affects craniofacial development.

New class of Son-of-sevenless (Sos) alleles highlights the complexities of Sos function.

The guanine nucleotide exchange factor (GEF) Son-of-sevenless (Sos) encodes a complex multidomain protein best known for its role in activating the small GTPase RAS in response to receptor tyrosine kinase (RTK) stimulation. Much less well understood is SOS's role in modulating RAC activity via a separate GEF domain. In the course of a genetic modifier screen designed to investigate the complexities of RTK/RAS signal transduction, a complementation group of 11 alleles was isolated and mapped to the Sos locus.

Splits ends is a tissue/promoter specific regulator of Wingless signaling.

Wingless directs many developmental processes in Drosophila by regulating expression of specific target genes through a conserved signaling pathway. Although many nuclear factors have been implicated in mediating Wingless-induced transcription, the mechanism of how Wingless regulates different targets in different tissues remains poorly understood. We report here that the split ends gene is required for Wingless signaling in the eye, wing and leg imaginal discs.