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CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex.

Proc Natl Acad Sci U S A

February 2025

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.

Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.

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Stem cell pluripotency gene Sox2 stimulates expression of proneural basic-helix-loop-helix transcription factor Atoh1. Sox2 is necessary for the development of cochlear hair cells and binds to the Atoh1 3' enhancer to stimulate Atoh1 expression. We show here that Sox2 deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after Sox2 knockout early in gestation.

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The suppression of tyrosinase (TYR), a key enzyme in melanogenesis, has been suggested as an effective strategy for preventing melanin accumulation. We previously discovered the novel chrysin derivative hydroxyethyl chrysin (HE-chrysin) through an irradiation technique, which exerted higher anti-inflammatory and anti-cancer activities than original chrysin. In the present study, we explored whether HE-chrysin has antioxidant and anti-melanogenic capacity using B16F10 murine melanoma cells and molecular docking.

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Background: The effects of multiple early adverse psychosocial and biological factors on child development at preschool age in deprived settings are not fully understood.

Methods: The 'Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development' (MAL-ED) project followed children from eight countries, recording sociodemographic, nutritional, illness, enteroinfection biomarkers and scores for quality of home environment (Home Observation for Measurement of the Environment (HOME)), development (Bayley) and maternal depression during the first year of life. In the Pakistan cohort, we investigated associations of these early factors with Z-scores (derived from the eight participating countries) of three developmental outcomes at 5 years: Executive Functions (Z-EF), the Wechsler Preschool and Primary Scale for Intelligence (Z-WPPSI) and the externalising behaviours component of the Strength and Difficulties test (Z-externalising behaviours).

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Elusive modes of Foxp3 activity in versatile regulatory T cells.

Front Immunol

January 2025

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, United States.

Foxp3-expressing CD4 regulatory T (Treg) cells play a crucial role in suppressing autoimmunity, tolerating food antigens and commensal microbiota, and maintaining tissue integrity. These multifaceted functions are guided by environmental cues through interconnected signaling pathways. Traditionally, Treg fate and function were believed to be statically determined by the forkhead box protein Foxp3 that directly binds to DNA.

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