Annals of the New York Academy of Sciences最新文献

Lipids are essential for brain development, functioning as both structural components of cell membranes and key signaling molecules. However, the regulatory mechanisms underlying lipid metabolism during neurodevelopment remain incompletely understood. The gene disconnected interacting protein 2 homolog C (DIP2C) localizes to human chromosome 10p15.3 and is associated with neurodevelopmental disorders. It encodes the protein DIP2C that contains both an acyl-CoA synthetase domain and an AMP-binding domain, which are involved in lipid metabolism. To investigate the role of DIP2C in neurodevelopment, we constructed both heterozygous and homozygous Dip2c mutant mice. Homozygous mutant mice exhibited weight loss, hyperlocomotion, cognitive impairment, and abnormal lipid metabolism, whereas heterozygous mutant mice displayed only mild cognitive impairment, recapitulating the dosage-sensitive phenotype observed in human 10p15.3 microdeletion syndrome. Mendelian randomization analysis suggested a positive causal relationship between linoleic acid and developmental disorders. Pathway enrichment analysis revealed a significant upregulation of sphingolipid metabolism in the cortex, accompanied by elevated oligodendrogenesis and myelination. This effect was likely due to increased expression of a key subunit of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid biosynthesis. Together, these findings identify DIP2C as a critical regulator of myelination and sphingolipid metabolic homeostasis during neurodevelopment, offering novel insight into neurodevelopmental disorders.

Creatinine is an important indicator of renal function, and its accurate and efficient detection is important to clinical diagnosis and disease monitoring. As the structure combining MXene layers and gold nanoparticles (AuNPs) provides many active sites and hot spots for surface-enhanced Raman scattering (SERS), ultrasensitive detection of creatinine can be realized. Herein, homogeneous ultrathin Ti₃C₂-MXene films are produced on a large scale by interfacial self-assembly, and a uniformly distributed AuNP monolayer and three-dimensional ribbon-like AuNP assemblies (RAuNPs) are then separately assembled on the MXene surface by simply regulating the nanoparticle concentration and the drying temperature. The two SERS substrates of AuNPs/MXene and RAuNPs/MXene are capable of sensitive detection of creatinine in aqueous solutions without labels. The SERS activity is verified using Rhodamine 6G (R6G). In the SERS detection of creatinine, the AuNPs/MXene substrate shows a linear range from 1 × 10⁻⁴ to 1 × 10⁻⁸ M with a limit of detection (LOD) of 287 nM, whereas the RAuNPs/MXene substrate exhibits a good linear relationship in the range from 1 × 10⁻³ to 1 × 10⁻¹⁰ M with a LOD of 2.64 nM. The outstanding SERS properties of RAuNPs/MXene suggest promising potential pertaining to the rapid and sensitive detection of creatinine.

Accurately recognizing auditory targets within background interference remains challenging at a low signal-to-noise ratio (SNR). Using an oddball paradigm, this electroencephalogram study investigated the impact of SNR (0, −10, and −20 dB) on psychophysiological processes underlying underwater auditory target recognition in twenty normal-hearing participants. Reduced SNR impaired the N1–P2 component and led to P300 variations, with delayed latencies (N1: p = 0.0355; P300: p = 0.0075) and reduced amplitudes (P2: p = 0.0075; P300: p = 0.0277), indicating increased attentional demands. Microstate analysis highlighted 300–400 ms frontoparietal activation for attention orientation and sensory information integration. Reduced accuracy correlates with alpha-band activity and phase variations over frontoparietal areas (event-related spectral perturbation [ERSP]: p = 0.0388; inter-trial coherence [ITC]: p = 0.0059), implying suppression of task-relevant processing. Gamma-band activity and phase at lower SNR levels suggest changes in the parietal network's function (ERSP: p = 0.0183; ITC: p = 0.0113), influencing reaction times due to increased integration difficulty. Right-lateralized alpha- and gamma-band network shifts support the functional advantages of the right hemisphere in noise, with enhanced local efficiency (frontal alpha: p = 0.0100; parietal—occipital gamma: p = 0.0116). These findings provide insights into the psychophysiological mechanisms underlying auditory target recognition in noise.

The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.

The assessment of the degree of nasal obstruction is valuable in disease diagnosis, quality of life assessment, and epidemiological studies. To this end, this article proposes a multimodal nasal obstruction degree classification model based on cone beam computed tomography (CBCT) images and nasal resistance measurements. The model consists of four modules: image feature extraction, table feature extraction, feature fusion, and classification. In the image feature extraction module, this article proposes a strategy of using the trained MedicalNet large model to get the pre-training parameters and then migrating them to the three-dimensional convolutional neural network (3D CNN) feature extraction model. For the nasal resistance measurement form data, a method based on extreme gradient boosting (XGBoost) feature importance analysis is proposed to filter key features to reduce the data dimension. In order to fuse the two types of modal data, a feature fusion method based on local and global features was designed. Finally, the fused features are classified using the tabular network (TabNet) model. In order to verify the effectiveness of the proposed method, comparison experiments and ablation experiments are designed, and the experimental results show that the accuracy and recall of the proposed multimodal classification model reach 0.93 and 0.9, respectively, which are significantly higher than other methods.

When parent-accused child sexual abuse allegations co-occur with parent conflict, concerns arise that the allegations are fabricated by the child's non-accused parent. However, no prior research has directly examined how parent conflict influenced credibility in parent-accused child sexual abuse cases. There are also discrepant research findings on how accused parent gender and decision-makers’ gender-based beliefs influenced allegation credibility in parent-accused abuse and conflict cases. We examined how parent conflict (low, high), accused parent (father, mother, mother's boyfriend), and participants’ belief in sexism shift (BSS) (belief that men are now the primary targets of sexism) influenced allegation credibility. High parent conflict significantly reduced allegation credibility and did not significantly interact with the accused parent or participants’ BSS. Allegations against the mother were rated least credible, followed by the father, and allegations against the mother's boyfriend were rated most credible. This, however, was moderated by participants’ BSS: those with high endorsement of BSS rated allegations against the father as least credible. Legal professionals working with parent-accused child sexual abuse cases should critically consider how parent conflict, the accused parent, and their gender-based beliefs influence their decisions in ways that are not grounded in the facts of the case.

Crimean-Congo hemorrhagic fever (CCHF) is prevalent in Africa, Asia, and Europe and poses a serious and long-standing public health burden. Europe, especially Russia, Turkey, and the Balkan region, has been a hotspot for the disease, with the most confirmed reports. Crimean-Congo hemorrhagic fever virus (CCHFV), the etiological agent of the disease, shows general delineation of phylogeography among the CCHF-epidemic areas. The isolates of lineage Europe 1 represent the majority of the agent in Europe and primarily circulate in the Russia–Turkey–Balkan region. To decipher the molecular basis of the CCHF epidemicity in Europe, I analyzed the genetic diversification of lineage Europe 1 isolates. Contingency analysis with the reconstructed ancestral sequences of the large (L) and medium (M) segments showed that, in the early epidemic of the lineage, rapid diversification occurred in the nonstructural M protein of the M segment. The McDonald−Kreitman test, together with contingency analysis, showed that nucleoprotein of the small (S) segment achieved an acceleration of amino acid substitutions in this process. These findings offer a molecular perspective on CCHFV epidemicity, at least in Europe, and highlight the key viral factors that could have contributed to the emergence of lineage Europe 1.