Annals of the New York Academy of Sciences最新文献

Thiamine (vitamin B1) deficiency due to degradation, inadequate intake, impaired absorption, or increased metabolic demand remains prevalent in both human and animal populations. In its diphosphate form (thiamine diphosphate, TDP), thiamine serves as an essential cofactor for metabolic enzymes, including transketolase (TKT), a rate-limiting enzyme of the pentose-phosphate pathway. Measurement of TKT activity with and without exogenous TDP provides a functional assessment of thiamine utilization that serves as a surrogate for or complements direct quantification of thiamine forms. Beyond its historical role as a deficiency-screening tool, the TKT assay offers opportunities to interrogate enzyme function and cofactor dependence. Strategic variation of assay conditions, such as higher TDP concentrations to identify low-affinity TKT variants or including or omitting magnesium to assess functional cofactor limitation, can distinguish true deficiency from impaired enzyme utilization or altered enzyme properties. This review evaluates preanalytical variables, assay methodologies, and data presentation strategies used for TKT measurements in erythrocytes and other tissues across human and nonhuman studies. Emphasis is placed on biological and methodological determinants that shape measured activity and responsiveness. Improved interpretation frameworks and thoughtful assay design can expand the utility of TKT measurements as indicators of functional thiamine status across clinical, translational, and ecological contexts.

The biological origins of meditation in humans remain underexplored, despite extensive scholarship on its cultural history and health effects. We present a theoretical account that traces the origins of meditation to the evolutionarily conserved repertoire of defensive freezing. We propose that this ancient survival response-characterized by motoric immobility, heightened vigilance with narrowed attentional focus, and bradycardia-provided a behavioral, neural, and physiological substrate upon which operant and social reinforcement could act. Over evolutionary time, these response components may have been co-opted and selectively reinforced within early human social communities, giving rise to complex, structured behavioral repertoires resembling modern sitting and slow-movement meditative practices embedded within various cultural systems of teaching. Rather than viewing meditation as a human psychological innovation, we suggest it represents a culturally refined expression of an ancestral survival strategy, maintained and elaborated through reinforcement, mimicry, and verbal instruction, spanning the late Paleolithic era (approximately 150,000-200,000 years before present) to the present day. This framework recasts meditation as an evolved modulation of a more basic stress- and threat-related freezing response template, shaped and maintained through social reinforcement.

Bacteroides fragilis is a key component of the human gut microbiota, although enterotoxigenic strains (ETBF), which produce B. fragilis toxin (BFT), can act as opportunistic pathogens. BFT disrupts intestinal epithelial integrity and contributes to conditions such as inflammatory bowel disease and colorectal cancer. This study aimed to characterize three allosteric inhibitors of BFT-3 (isoform 3 of BFT), previously identified by our group through high-throughput screening of US Food and Drug Administration approved drugs. We evaluated their activities in vitro and in vivo. Using Galleria mellonella larvae as a novel infection model for B. fragilis, we assessed the antimicrobial and antivirulence potential of these compounds. Among the three tested compounds, MOA4 demonstrated superior efficacy, enhanced bacterial clearance in vivo, and increased larval survival in a dose-dependent manner, with minimal toxicity. Synergy studies have revealed the potential combinatory effects of MOA4 and conventional antibiotics. These findings establish G. mellonella as a valuable alternative model for studying B. fragilis infections and highlight MOA4 as a promising candidate to be repurposed for the treatment of B. fragilis-mediated diseases while preserving commensal microbiota.

To evaluate an individuals' moral character the intentions behind their actions must be discriminated from the actual outcome. How this is achieved remains unclear. We developed a novel paradigm that dissociates the perception of intentions from outcome. Participants separately predicted and received feedback on agents' intentions and outcomes. They then made moral evaluations of the agent. Four independent experiments (120 participants in total) demonstrated that intentions and outcomes mutually influenced each other during the learning process before integrating them for subsequent moral evaluation. Computational modeling further revealed that intentions biased the predictions of outcomes, while outcomes directly modified the beliefs about intentions. Moreover, participants considered both intention and outcome when making moral evaluations, but placed greater weight on intention, regardless of sampling bias and presentation order. These findings offer new insights concerning how individuals process intention and outcome when learning about others' moral character.

Accurate kidney tumor segmentation is critical for surgical planning but is challenged by indistinct boundaries and high morphological variability in computed tomography (CT) images. We propose the adaptive boundary-aware network (MABS-Net). The architecture integrates three core innovations: (1) a boundary-aware multiscale feature extraction module using learnable boundary-enhancing convolutions and adaptive weight maps to capture subtle edge cues; (2) an adaptive three-stage cascaded strategy for progressive refinement from coarse localization to uncertainty-driven boundary optimization; and (3) a contrastive learning mechanism with online hard example mining to explicitly boost feature discrimination between tumor and normal tissues in ambiguous regions. Experiments on the KiTS19 and KiTS21 datasets demonstrate MABS-Net's superiority. On KiTS19, it achieved a Dice coefficient of 0.891 ± 0.034, significantly outperforming the nnU-Net baseline. Notably, the 95% Hausdorff distance (HD95) was reduced to 6.73 ± 2.28 mm, and the boundary Dice score improved by 5.8% compared to state-of-the-art methods, validating our boundary-aware design. Furthermore, the model provides pixel-wise uncertainty maps to support reliable clinical decision-making. MABS-Net balances high accuracy with computational efficiency (0.53 s/case), presenting a promising solution for automated renal tumor analysis.