Development of brain state dynamics involved in working memory.

Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure-function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.

Default mode network scaffolds immature frontoparietal network in cognitive development.

The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children's DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.

Developmental Sex Differences in Negative Emotion Decision-Making Dynamics: Computational Evidence and Amygdala-Prefrontal Pathways.

Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

The Moonlighting Function of Soybean Disordered Methyl-CpG-Binding Domain 10c Protein.

Intrinsically disordered proteins (IDPs) are multifunctional due to their ability to adopt different structures depending on the local conditions. The intrinsically disordered regions of methyl-CpG-binding domain (MBD) proteins play important roles in regulating growth and development by interpreting DNA methylation patterns. However, whether MBDs have a stress-protective function is far from clear. In this paper, soybean GmMBD10c protein, which contains an MBD and is conserved in Leguminosae, was predicted to be located in the nucleus. It was found to be partially disordered by bioinformatic prediction, circular dichroism and a nuclear magnetic resonance spectral analysis. The enzyme activity assay and SDS-PAGE results showed that GmMBD10c can protect lactate dehydrogenase and a broad range of other proteins from misfolding and aggregation induced by the freeze-thaw process and heat stress, respectively. Furthermore, overexpression of GmMBD10c enhanced the salt tolerance of Escherichia coli. These data validate that GmMBD10c is a moonlighting protein with multiple functions.

Beyond a Linker: The Role of Photochemistry of Crosslinkers in the Direct Optical Patterning of Colloidal Nanocrystals.

Surface chemistry mediated direct optical patterning represents an emerging strategy for incorporating colloidal nanocrystals (NCs) in integrated optoelectronic platforms including displays and image sensors. However, the role of photochemistry of crosslinkers and other photoactive species in patterning remains elusive. Here we show the design of nitrene- and carbene-based photocrosslinkers can strongly affect the patterning capabilities and photophysical properties of NCs, especially quantum dots (QDs). Their role beyond physical linkers stems from structure-dictated electronic configuration, energy alignment and associated reaction kinetics and thermodynamics. Patterned QD layers with designed carbene-based crosslinkers fully preserve their photoluminescent and electroluminescent properties. Patterned light emitting diodes (QLEDs) show a maximum external quantum efficiency of ≈12 % and lifetime over 4800 h, among the highest for reported patterned QLEDs. These results would guide the rational design of photoactive species in NC patterning and create new possibilities in the monolithic integration of NCs in high-performance device platforms.

Harmine targets inhibitor of DNA binding-2 and activator protein-1 to promote preosteoclast PDGF-BB production.

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet-derived growth factor-BB (PDGF-BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF-BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding-2 (Id2) and activator protein-1 (AP-1) were important factors implicated in harmine-enhanced preosteoclast PDGF-BB production. Exposure of RANKL-induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP-1. Knockdown of Id2 by Id2-siRNA reduced the number of preosteoclasts as well as secretion of PDGF-BB in RANKL-stimulated BMMs administrated with harmine. Inhibition of c-Fos or c-Jun (components of AP-1) both reversed the stimulatory effect of harmine on preosteoclast PDGF-BB production. Dual-luciferase reporter assay analyses determined that PDGF-BB was the direct target of AP-1 which was up-regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF-BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.

Quantum dot solids showing state-resolved band-like transport.

Improving charge mobility in quantum dot (QD) films is important for the performance of photodetectors, solar cells and light-emitting diodes. However, these applications also require preservation of well defined QD electronic states and optical transitions. Here, we present HgTe QD films that show high mobility for charges transported through discrete QD states. A hybrid surface passivation process efficiently eliminates surface states, provides tunable air-stable n and p doping and enables hysteresis-free filling of QD states evidenced by strong conductance modulation. QD films dried at room temperature without any post-treatments exhibit mobility up to µ ~ 8 cm2 V-1 s-1 at a low carrier density of less than one electron per QD, band-like behaviour down to 77 K, and similar drift and Hall mobilities at all temperatures. This unprecedented set of electronic properties raises important questions about the delocalization and hopping mechanisms for transport in QD solids, and introduces opportunities for improving QD technologies.

Automatic detection of leakage point in central serous chorioretinopathy of fundus fluorescein angiography based on time sequence deep learning.

PURPOSE: To detect the leakage points of central serous chorioretinopathy (CSC) automatically from dynamic images of fundus fluorescein angiography (FFA) using a deep learning algorithm (DLA). METHODS: The study included 2104 FFA images from 291 FFA sequences of 291 eyes (137 right eyes and 154 left eyes) from 262 patients. The leakage points were segmented with an attention gated network (AGN). The optic disk (OD) and macula region were segmented simultaneously using a U-net. To reduce the number of false positives based on time sequence, the leakage points were matched according to their positions in relation to the OD and macula. RESULTS: With the AGN alone, the number of cases whose detection results perfectly matched the ground truth was only 37 out of 61 cases (60.7%) in the test set. The dice on the lesion level were 0.811. Using an elimination procedure to remove false positives, the number of accurate detection cases increased to 57 (93.4%). The dice on the lesion level also improved to 0.949. CONCLUSIONS: Using DLA, the CSC leakage points in FFA can be identified reproducibly and accurately with a good match to the ground truth. This novel finding may pave the way for potential application of artificial intelligence to guide laser therapy.

5-Hydroxytryptamine (5-HT)-exacerbated DSS-induced colitis is associated with elevated NADPH oxidase expression in the colon.

AIM: This study investigated the impact of 5-hydroxytryptamine (5-HT) on the expression of NOXs in dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6J (B6) mice at 6 to 8 weeks of age were treated with 5-HT, DSS, or DSS + 5-HT. After 6-day treatment, the severity of colitis, infiltration of leukocytes, and messenger RNA (mRNA) and/or protein levels of Nox1, Nox2, Nox4, and Duox2 were analyzed in the colon by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blot analysis. The direct effect of 5-HT on NOX gene and protein expression in HT-29 colon cancer cells and in U-937 macrophage cells were determined by qPCR and Western blot analysis. RESULTS: Mice treated with 5-HT alone did not develop colitis, while those treated with 1.0% DSS or DSS + 5-HT had mild and severe colitis, respectively. All treated mice had more myeloperoxidase-positive cells in the colon compared with untreated control mice. Mice treated with 5-HT or DSS alone had increased Nox2 and Nox4 mRNA and protein levels in the colon determined by qPCR, IHC, and Western blot analysis. These two Nox expressions were even higher in mice treated with DSS + 5-HT, while the expression levels of epithelium-localized Nox1 and Duox2 tended to decrease. Additionally, mice treated with 5-HT alone had elevated Nox1 and Duox2 expression as shown by qPCR and IHC. However, these gene expressions were diminished in DSS + 5-HT-treated mice likely due to erosion of epithelium. Furthermore, 5-HT induced NOX1 and DUOX2 gene and protein expression in HT-29 colon cancer epithelial cells, whereas induced NOX2 and NOX4 gene and protein expression in U-937 cells. CONCLUSION: As 5-HT induced NOX1 and DUOX2 gene and protein expression in colon epithelial and HT-29 cells, NOX2 and NOX4 in the infiltrating leukocyte in mouse colon and in U-937 cells, the exacerbate colitis induced by combined 5-HT and DSS treatment might be relevant to increased NOX expression in mice colons.

Quantitative Assessment and Diagnosis for Regional Agricultural Drought Resilience Based on Set Pair Analysis and Connection Entropy.

Assessment and diagnosis of regional agricultural drought resilience (RADR) is an important groundwork to identify the shortcomings of regional agriculture to resist drought disasters accurately. In order to quantitatively assess the capacity of regional agriculture system to reduce losses from drought disasters under complex conditions and to identify vulnerability indexes, an assessment and diagnosis model for RADR was established. Firstly, this model used the improved fuzzy analytic hierarchy process to determine the index weights, then proposed an assessment method based on connection number and an improved connection entropy. Furthermore, the set pair potential based on subtraction was used to diagnose the vulnerability indexes. In addition, a practical application had been carried out in the region of the Huaibei Plain in Anhui Province. The evaluation results showed that the RADR in this area from 2005 to 2014 as a whole was in a relatively weak situation. However, the average grade values had decreased from 3.144 to 2.790 during these 10 years and the RADR had an enhanced tendency. Moreover, the possibility of RADR enhancement for six cities in this region decreased from east to west, and the drought emergency condition was the weak link of the RADR in the Huaibei Plain.

Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin-Induced Nephrotoxicity In Vivo and In Vitro.

BACKGROUND/AIMS: The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity. METHODS: In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI). Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro. RESULTS: Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. The expressions of the two biomarkers changed prior to renal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo. CONCLUSIONS: In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.

Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon.

Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation. Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis. Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons. Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro. Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.

KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats.

Gentamicin is a member of aminoglycosides, which has represented highly effective antimicrobial agents especially in Gram-negative infections despite their toxic effects in the kidney. Rapid diagnosis is vital to preserve renal function and to slow down renal injury. Owing to the poor sensitivity and specificity of serum creatinine (SCr) and blood urea nitrogen (BUN), new biomarkers for earlier and more accurate detection are needed. The aim of our study was to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful biomarkers in the assessment of gentamicin-induced nephrotoxicity in rats. In this study, the two biomarkers of renal toxicity were assessed via ELISA, quantitative real-time PCR, and immunohistochemistry in rats treated with gentamicin for up to 7 days. Repeated administration of gentamicin to male SD rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. Changes in gene and protein expressions were found to correlate with the progressive histopathological alterations and preceded effects on traditional clinical parameters indicative of impaired kidney function. Both of the biomarkers are supported to be used as sensitive indicators of acute kidney injury caused by gentamicin.

Colloidal Quantum Dots for Nanophotonic Devices.

Colloidal quantum dots (CQDs) have unique advantages in the wide tunability of visible-to-infrared emission wavelength and low-cost solution processibility [...].

Very long wave infrared quantum dot photodetector up to 18 µm.

Colloidal quantum dots (CQDs) are of interest for optoelectronic devices because of the possibility of high-throughput solution processing and the wide energy gap tunability from ultraviolet to infrared wavelengths. People may question about the upper limit on the CQD wavelength region. To date, although the CQD absorption already reaches terahertz, the practical photodetection wavelength is limited within mid-wave infrared. To figure out challenges on CQD photoresponse in longer wavelength, would reveal the ultimate property on these nanomaterials. What's more, it motivates interest in bottom-up infrared photodetection with less than 10% cost compared with epitaxial growth semiconductor bulk. In this work, developing a re-growth method and ionic doping modification, we demonstrate photodetection up to 18 µm wavelength on HgTe CQD. At liquid nitrogen temperature, the responsivity reaches 0.3 A/W and 0.13 A/W, with specific detectivity 6.6 × 108 Jones and 2.3 × 109 Jones for 18 µm and 10 µm CQD photoconductors, respectively. This work is a step toward answering the general question on the CQD photodetection wavelength limitation.

UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.

Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.

In Situ Growth Method for Large-Area Flexible Perovskite Nanocrystal Films.

Metal halide perovskites have shown unique advantages compared with traditional optoelectronic materials. Currently, perovskite films are commonly produced by either multi-step spin coating or vapor deposition techniques. However, both methods face challenges regarding large-scale production. Herein, we propose a straightforward in situ growth method for the fabrication of CsPbBr3 nanocrystal films. The films cover an area over 5.5 cm × 5.5 cm, with precise thickness control of a few microns and decent uniformity. Moreover, we demonstrate that the incorporation of magnesium ions into the perovskite enhances crystallization and effectively passivates surface defects, thereby further enhancing luminous efficiency. By integrating this approach with a silicon photodiode detector, we observe an increase in responsivity from 1.68 × 10-2 A/W to 3.72 × 10-2 A/W at a 365 nm ultraviolet wavelength.

Tuning zinc content in wollastonite bioceramic endowing outstanding angiogenic and antibacterial functions beneficial for orbital reconstruction.

Prosthetic eye is indispensable as filler after enucleation in patients with anophthalmia, whereas there are still many complications including postoperative infection and eye socket depression or extrusion during the conventional artificial eye material applications. Some Ca-silicate biomaterials showed superior bioactivity but their biological stability in vivo limit the biomedical application as long-term or permanent implants. Herein we aimed to understand the physicochemical and potential biological responses of zinc doping in wollastonite bioceramic used for orbital implants. The wollastonite powders with different zinc dopant contents (CSi-Znx) could be fabricated as porous implants with strut or curve surface pore geometries (cubic, IWP) via ceramic stereolithography. The experimental results indicated that, by increasing zinc-substituting-Ca ratio (up to 9%), the sintering and mechanical properties could be significantly enhanced, and meanwhile the bio-dissolution in vitro and biodegradability in vivo were thoroughly inhibited. In particular, an appreciable angiogenic activity and expected antibacterial efficacy (over 90 %) were synergistically achieved at 9 mol% Zn dopant. In the back-embedding and enucleation and implantation model experiments in rabbits, the superior continuous angiogenesis was corroborated from the 2D/3D fibrovascular reconstruction in the IWP-pore CSi-Zn9 and CSi-Zn13.5 groups within very short time stages. Totally, the present silicate-based bioceramic via selective Zn doping could produce outstanding structural stability and bifunctional biological responses which is especially valuable for developing the next-generation implants with vascular insertion and fixation in orbital reconstruction prothesis.

Development of the triadic neural systems involved in risky decision-making during childhood.

Risk-taking often occurs in childhood as a compex outcome influenced by individual, family, and social factors. The ability to govern risky decision-making in a balanced manner is a hallmark of the integrity of cognitive and affective development from childhood to adulthood. The Triadic Neural Systems Model posits that the nuanced coordination of motivational approach, avoidance and prefrontal control systems is crucial to regulate adaptive risk-taking and related behaviors. Although widely studied in adolescence and adulthood, how these systems develop in childhood remains elusive. Here, we show heterogenous age-related differences in the triadic neural systems involved in risky decision-making in 218 school-age children relative to 80 young adults. Children were generally less reward-seeking and less risk-taking than adults, and exhibited gradual increases in risk-taking behaviors from 6 to 12 years-old, which are associated with age-related differences in brain activation patterns underlying reward and risk processing. In comparison to adults, children exhibited weaker activation in control-related prefrontal systems, but stronger activation in reward-related striatal systems. Network analyses revealed that children showed greater reward-related functional connectivity within and between the triadic systems. Our findings support an immature and unbalanced developmental view of the core neurocognitive systems involved in risky decision-making and related behaviors in middle to late childhood.