Common modular architecture across diverse cortical areas in early development.

In order to deal with a complex environment, animals form a diverse range of neural representations that vary across cortical areas, ranging from largely unimodal sensory input to higher-order representations of goals, outcomes, and motivation. The developmental origin of this diversity is currently unclear, as representations could arise through processes that are already area-specific from the earliest developmental stages or alternatively, they could emerge from an initially common functional organization shared across areas. Here, we use spontaneous activity recorded with two-photon and widefield calcium imaging to reveal the functional organization across the early developing cortex in ferrets, a species with a well-characterized columnar organization and modular structure of spontaneous activity in the visual cortex. We find that in animals 7 to 14 d prior to eye-opening and ear canal opening, spontaneous activity in both sensory areas (auditory and somatosensory cortex, A1 and S1, respectively), and association areas (posterior parietal and prefrontal cortex, PPC and PFC, respectively) showed an organized and modular structure that is highly similar to the organization in V1. In all cortical areas, this modular activity was distributed across the cortical surface, forming functional networks that exhibit millimeter-scale correlations. Moreover, this modular structure was evident in highly coherent spontaneous activity at the cellular level, with strong correlations among local populations of neurons apparent in all cortical areas examined. Together, our results demonstrate a common distributed and modular organization across the cortex during early development, suggesting that diverse cortical representations develop initially according to similar design principles.

Associations between Vitamin D Levels and Insulin Resistance in Non-Diabetic Obesity: Results from NHANES 2001-2018.

OBJECTIVE: Obesity is often accompanied by insulin resistance (IR) and diabetes. We explored the association between vitamin D levels and IR in non-diabetic obesity. METHODS: We conducted a cross-sectional study based on the data of National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. Non-diabetic individuals (aged ≥20 years) with obesity (BMI ≥ 30kg/m2) were included in the study. And HOMA-IR ≥ 2.5 was defined as IR. The multivariable linear regression models were constructed to evaluate the associations between levels of 25(OH)D and HOMA-IR. We calculated the odds ratio (OR) and 95% confidential intervals (CIs) for associations between 25(OH)D deficiency and IR in obesity using multivariable logistic regression models. RESULTS: Overall, a total of 3887 individuals were included in this study. Serum vitamin D level was significant lower in obesity participants with IR than that of non-IRs. The linear regression models showed that vitamin D level was inversely associated with HOMA-IR in obesity after adjusting for covariables (ß=-0.15, 95%CI (-0.28, -0.02), p = 0.028). And the multivariable logistic regression models indicated an association between vitamin D deficiency and IR in obesity ((OR= 1.38, 95%CI (1.09-1.73), p = 0.007)). The further stratified regression analyses among different BMI demonstrated that vitamin D deficiency (OR = 1.4, 95%CI (1.05,1.86), p = 0.022) only contributed to developing IR in class I obesity. CONCLUSION: This study suggested an association of vitamin D levels with IR in obesity. And vitamin D deficiency contributed to IR in class I obesity.

Developmental maturation of millimeter-scale functional networks across brain areas.

Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using in vivo widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory-V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization-known to encode functional representations in visual areas-may be similarly engaged in highly diverse brain areas.

Toxic effects of environmentally persistent free radicals (EPFRs) on the surface of tire wear particles on freshwater biofilms: The alleviating role after sewage-incubation-aging.

The aquatic ecological risks posed by the surface-active components of tire wear particles (TWPs) are not fully understood. This study aimed to determine the acute (24 h exposure) aquatic toxicity effects of TWPs on freshwater biofilms in terms of total organic carbon (TOC), chlorophyll-a (Chl-a) abundance, quantum yield (ФM), and adenosine triphosphate (ATP). Three types of TWP were tested: TWPs produced via the typical wear of tires and roads (i.e., rolling friction (R-TWPs) and sliding friction (S-TWPs)) and cryogenically milled tire treads (C-TWPs). The results showed that the surface structural properties of the three TWPs differed significantly in morphology, bare composition, functional groups, and surface-active components (environmental persistent free radicals). The exposure of biofilms to the TWPs increased TOC and ATP at low concentrations (1 mg L-1) but inhibited them at high concentrations (50 mg L-1). All TWP types inhibited biofilm photosynthesis (reduced Chl-a and ФM) and altered the community structure of algae to varying degrees; in addition, the toxicity mechanisms of the TWPs contributed to the accumulation of reactive oxygen species and cell membrane (or cell-wall) fragmentation, leading to lactate dehydrogenase release. S-TWPs were the most toxic because their surface carried the highest environmental persistent free radicals. R-TWPs were the second most toxic, which was attributed to their smaller particle size. The toxicity of all TWPs was tested after sewage incubation aging. The results showed that the toxicity of all TWPs reduced as the sewage covered their surface components and active sites. This process also reduced the differences in toxicity among the TWPs. This study filled a research gap in our understanding of aquatic toxicity caused by the surface structural properties of tire microplastics and has implications for the study of microplastic biotoxicity mechanisms.

Differential cytotoxicity to human cells in vitro of tire wear particles emitted from typical road friction patterns: The dominant role of environmental persistent free radicals.

Tire wear particles (TWPs) have been recognized as one of the major sources of microplastics (MPs), however, effects of initial properties and photochemical behavior of TWPs on cytotoxicity to human cells in vitro have not been reported. Therefore, here, three TWPs generated from typical wear of tires and pavements (i.e., rolling friction (R-TWPs) and sliding friction (S-TWPs)) and cryogenically milled tire tread (C-TWPs), respectively, and their photoaging counterparts were used to study the reasons for their differential cytotoxicity to 16HBE cells in vitro. Results showed in addition to changes of surface structure and morphology, different preparation methods could also induce formation of different concentration levels of environmental persistent free radicals (EPFRs) (from 1.24 to 3.06 × 1017 spins/g with g-factors ranging 2.00307-2.00310) on surfaces of TWPs, which contained 7.3%-65.8% of reactive EPFRs (r-EPFRs). Meanwhile, photoaging for 90 d could strengthen formation of EPFRs (from 4.03 to 4.61 × 1017 spins/g) with containing 74.7%-78.1% r-EPFRs on surfaces of TWPs and improve their g-factor indexes (ranging 2.00309-2.00313). At 100 µg mL-1 level, compared to C-TWPs, both R-TWPs and S-TWPs (whether photoaging or not) carried higher intensity EPFRs could significantly inhibit 16HBE cells proliferation activity, cause more cells oxidative stress and induce more cell apoptosis/necrosis and secretion of inflammatory factor (P < 0.05). However, regardless of how TWPs were prepared, photoaged or not, exposure at a concentration of 1 µg mL-1 appeared to be non-acute cytotoxic. Correlation analysis suggested dominant toxicity of TWPs was attributed to the formation of r-EPFRs on their surfaces, which could promote accumulation of excess reactive oxygen species in cells and the massive deposition of intracellular particles. This study provides direct evidence of TWPs cytotoxicity, and underlining the need for a better understanding of the influences of initial properties and photochemical characteristics on risk assessment of TWPs released into the environment.

Effects of tire wear particles with and without photoaging on anaerobic biofilm sulfide production in sewers and related mechanisms.

Tire wear particles (TWPs) are considered to be one of the major sources of microplastics (MPs) in sewers; however, little has been reported on the surface properties and photochemical behavior of TWPs, especially in terms of their environmental persistent radicals, leachate type, and response after photoaging. It is also unknown how TWPs influence the production of common pollutants (e.g., sulfides) in anaerobic biofilms in sewers. In our study, the effects of cryogenically milled tire treads (C-TWPs) and their corresponding photoaging products (photoaging-TWPs, A-TWPs) on anaerobic biofilm sulfide production in sewers and related mechanisms were studied. The results showed that the two TWPs at a low concentration (0.1 mg L-1) exerted no significant (p > 0.05) effects on sulfide yield, whereas exposure to a high concentration of TWPs (100 mg L-1) inversely affected sulfide yield, with A-TWPs exerting a significant inhibitory effect on sulfide yield in the sewers (p < 0.01). The main reason was that A-TWPs carried higher concentrations of reactive environmental persistent radicals on their surfaces after photoaging than C-TWPs, which could induce the formation of oxygen radicals. In addition, A-TWPs were more uniformly distributed in the wastewater system and could penetrate the biofilm to damage bacterial cells, and their ability to leach polycyclic aromatic hydrocarbons and heavy metals such as zinc additives enhanced their toxic effects. In contrast, C-TWPs contributed significantly to sulfide production (p < 0.01), primarily because of their low biotoxicity, ability to leach a considerable amount of sulfide, and stimulatory effect on anaerobic biofilm surface sulfate-reducing bacteria. Our study complements the toxicity studies of the TWPs particles themselves and provides insight on a new influencing factor for determining the changes in sulfide generation and control measures in sewers.