[Identification and the Related Molecular Mechanism of B(A)04 Allele].

OBJECTIVE: To investigate the identification and molecular biological mechanism of a case of B(A)04 allele. METHODS: The ABO blood groups of the proband and his nine family members were analyzed serologically and DNA sequencing was used to accurately determine the genotypes of these ten specimens. The cartoon models of local active center of enzymes of the GTA,GTB and the GTB mutant were constructed to explore the possible molecular mechanism leading to abnormal enzyme-catalyzed A antigen synthesis. RESULTS: The serological results suggested that the ABO blood groups of the proband, his elder brother and his maternal grandmother were AweakB or B(A); the ABO blood group of his mother was type AB, his uncle and elder aunt were type B, and his father was type O. ABO blood group gene sequencing results showed that 6 out of 10 members of the family carried the B(A)04 allele. Molecular structure models suggested that the spatial distance of critical amino acid residues in the catalytic center of the GTB mutant enzyme was greater than that of GTB, which might cause the enzyme to abnormally catalyze the synthesis of A antigen. CONCLUSION: The characteristics of serological reactions of B(A) blood subgroup are complicated, and its identification needs to be combined with molecular biology and pedigree investigation. It is speculated that the B(A) phenotype may be associated with a larger volume of the catalytic center in the GTB mutant.

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects.

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. The review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy.

Determination of the stable isotope discrimination factor of wild organisms: a case study of the red swamp crayfish in integrated rice-crayfish (Procambarus clarkii) culture without artificial diets.

This study collected samples from a 95-day integrated rice-crayfish culture experiment, and determined the stable isotope discrimination factor of the red swamp crayfish (Procambarus clarkii) by using a model method and difference value method. The isotope ratios of P. clarkii and the dietary resources in rice fields and its feeding niche volumes were 'conservative' as proposed. This result broadly supported the assumption of the laboratory feeding experiment that animals should be fed a single diet exhibiting a constant isotopic composition. Using standard ellipse areas (SEA) to screen the data, growth- and time-dependent models of carbon and nitrogen isotopes of females and males were obtained. The Δ13C and its half-lives for females and males were 0.67 (21.0 d) and 0.91 (33.0 d), whereas Δ15N and its half-lives for those were 3.45 (17.8 d) and 3.05 (17.3 d), respectively. The results of integrated rice-crayfish culture without artificial diets provides a reference example for future studies on species-specific discrimination factors in specific field habitats.

Identification of the novel HLA-B*15:625 allele in a Chinese marrow donor.

A novel HLA allele HLA-B*15:625 was identified in a Chinese marrow donor.

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats.

With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1ß secretion in vivo. NiONP-induced IL-1ß secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs.