Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR). We further show that Klf4 contributes to Cd34+/Fxyd5+/Psca+ keratinocyte-like NR fate and that IFN-γ impedes the final transition to chimera-competent pluripotency along the RP cells. We analyze more than 150,000 single cells from both OSK and chemical reprograming and identify additional NR/RP bifurcation points. Our work reveals a generic bifurcation model for cell fate decisions during somatic cell reprogramming that may be applicable to other systems and inspire further improvements for reprogramming.

Suppression of distracting inputs by visual-spatial cues is driven by anticipatory alpha activity.

A growing body of research demonstrates that distracting inputs can be proactively suppressed via spatial cues, nonspatial cues, or experience, which are governed by more than one top-down mechanism of attention. However, how the neural mechanisms underlying spatial distractor cues guide proactive suppression of distracting inputs remains unresolved. Here, we recorded electroencephalography signals from 110 participants in 3 experiments to identify the role of alpha activity in proactive distractor suppression induced by spatial cues and its influence on subsequent distractor inhibition. Behaviorally, we found novel changes in the spatial proximity of the distractor: Cueing distractors far away from the target improves search performance for the target, while cueing distractors close to the target hampers performance. Crucially, we found dynamic characteristics of spatial representation for distractor suppression during anticipation. This result was further verified by alpha power increased relatively contralateral to the cued distractor. At both the between- and within-subjects levels, we found that these activities further predicted the decrement of the subsequent PD component, which was indicative of reduced distractor interference. Moreover, anticipatory alpha activity and its link with the subsequent PD component were specific to the high predictive validity of distractor cue. Together, our results reveal the underlying neural mechanisms by which cueing the spatial distractor may contribute to reduced distractor interference. These results also provide evidence supporting the role of alpha activity as gating by proactive suppression.

The proactive and reactive mechanisms of learned spatial suppression.

Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.

Auditory change detection and visual selective attention: association between MMN and N2pc.

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.

Polarization of the third harmonic emission from the filamentation of femtosecond cylindrical vector beams.

We experimentally generate a third harmonic (TH) vector optical field in deep ultraviolet wavelength range using femtosecond vector laser beams. The generated TH beams are characterized by analyzing the Stokes parameters with different input laser energies. The results show that the TH predominantly preserves the vector polarization distribution of the fundamental frequency beam. Moreover, the intensity profile of the TH exhibits a multiple-ring structure. A hybrid polarization pattern is observed in the TH, where the ellipticity is influenced by the input laser energy. Our work provides an effective and straightforward method for producing TH vector optical fields, which may facilitate potential applications such as micro/nanofabrication and super-resolution microscopy.

Identification of 10 differentially expressed and cuproptosis-related genes in immune infiltration and prognosis of thyroid carcinoma.

The association between the cuproptosis-related genes and the immune infiltration and their prognostic value in thyroid carcinoma is still unexplored. Bioinformatics analyses were performed with data obtained from the TCGA dataset. The aberrantly expressed genes were selected. KEGG and GO analyses were conducted to explore the enriched pathways of the up-regulated or down-regulated genes in thyroid carcinoma. Totally 1495 genes were differentially expressed (691 up-regulated, 804 down-regulated) in thyroid carcinoma (p<0.05). The 10 cuproptosis-related RNAs (DLD, LIAS, LIPT1, FDX1, DLAT, MTF1, PDHA1, CDKN2A, GLS and PDHB) were also demonstrated to be aberrantly expressed in thyroid carcinoma patients tissues. FDX1 expression was correlated with the overall survival in thyroid carcinoma patients (HR=0.4995, 95% CI: 0.2688-0.9285, p=0.0282). Further multivariate cox regression analysis revealed that DLD (HR=24.8869, 95% CI: 4.48772-138.01181, p=0.00024), and LIAS (HR=7.74092, 95% CI: 1.12194-53.40898, p=0.03783) were associated with the survival of thyroid carcinoma patients. The immune infiltration analysis demonstrated that significant correlation between the 10 cuproptosis-related genes and immune infiltration in thyroid carcinoma (p<0.01). We presented the expression profiles of dysregulated genes in thyroid carcinoma. The findings of our study highlighted the potential of cuproptosis-related genes as prognostic biomarkers for thyroid carcinoma.

Overactivated contextual visual perception and response to a single dose of methylphenidate in children with ADHD.

The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93 years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93 years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72 years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.

Prioritizing flexible working memory representations through retrospective attentional strengthening.

Previous work has proposed two potential benefits of retrospective attention on working memory (WM): target strengthening and non-target inhibition. It remains unknown which hypothesis contributes to the improved WM performance, yet the neural mechanisms responsible for this attentional benefit are unclear. Here, we recorded electroencephalography (EEG) signals while 33 participants performed a retrospective-cue WM task. Multivariate pattern classification analysis revealed that only representations of target features were enhanced by valid retrospective attention during retention, supporting the target strengthening hypothesis. Further univariate analysis found that mid-frontal theta inter-trial phase coherence (ITPC) and ERP components were modulated by valid retrospective attention and correlated with individual differences and moment-to-moment fluctuations on behavioral outcomes, suggesting that both trait- and state-level variability in attentional preparatory processes influence goal-directed behavior. Furthermore, task-irrelevant target spatial location could be decoded from EEG signals, indicating that enhanced spatial binding of target representation is vital to high WM precision. Importantly, frontoparietal theta-alpha phase-amplitude coupling was increased by valid retrospective attention and predicted the reduced random guessing rates. This long-range connection supported top-down information flow in the engagement of frontoparietal networks, which might organize attentional states to integrate target features. Altogether, these results provide neurophysiological bases that retrospective attention improves WM precision by enhancing flexible target representation and emphasize the critical role of the frontoparietal attentional network in the control of WM representations.

Information-based multivariate decoding reveals imprecise neural encoding in children with attention deficit hyperactivity disorder during visual selective attention.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Attentional orientation is a potential clinical diagnostic marker to aid in the early diagnosis of ADHD. However, the underlying pathophysiological substrates of impaired attentional orienting in childhood ADHD remain unclear. Electroencephalography (EEG) was measured in 135 school-age children (70 with childhood ADHD and 65 matched typically developing children) to directly investigate target localization during spatial selective attention through univariate ERP analysis and information-based multivariate pattern machine learning analysis. Compared with children with typical development, a smaller N2pc was found in the ADHD group through univariate ERP analysis. Children with ADHD showed a lower parieto-occipital multivariate decoding accuracy approximately 240-340 ms after visual search onset, which predicts a slower reaction time and larger standard deviation of reaction time. Furthermore, a significant correlation was found between N2pc and decoding accuracy in typically developing children but not in children with ADHD. These observations reveal that impaired attentional orienting in ADHD may be due to inefficient neural encoding responses. By using a personalized information-based multivariate machine learning approach, we have advanced the understanding of cognitive deficits in neurodevelopmental disorders. Our study provides potential research directions for the early diagnosis and optimization of personalized intervention in children with ADHD.

Experimentally determined critical power for self-focusing of femtosecond vortex beams in air by a fluorescence measurement.

The filamentation of the femtosecond vortex beam has attracted much attention because of the unique filamentation characteristics, such as annular distribution and helical propagation, and related applications. The critical power for self-focusing of the femtosecond vortex beams is a key parameter in the filamentation process and applications. But until now, there is no quantitative determination of the critical power. In this work, we experimentally determine the self-focusing critical power of femtosecond vortex beams in air by measuring fluorescence using a photomultiplier tube. The relation between the self-focusing critical power and the topological charge is further obtained. Our work provides a simple method to determine the self-focusing critical power not only for vortex beams but also for Airy, Bessel, vector, and other structured laser beams.

Distinguishing the nonlinear propagation regimes of vortex femtosecond pulses in fused silica by evaluating the broadened spectrum.

The nonlinear propagation dynamics of vortex femtosecond laser pulses in optical media is a topic with significant importance in various fields, such as nonlinear optics, micromachining, light bullet generation, vortex air lasing, air waveguide and supercontinuum generation. However, how to distinguish the various regimes of nonlinear propagation of vortex femtosecond pulses remains challenging. This study presents a simple method for distinguishing the regimes of nonlinear propagation of femtosecond pulses in fused silica by evaluating the broadening of the laser spectrum as the input pulse power gradually increases. The linear, self-focusing and mature filamentation regimes for Gaussian and vortex femtosecond pulses in fused silica are distinguished. The critical powers for self-focusing and mature filamentation of both types of laser pulses are obtained. Our work provides a rapid and convenient method for distinguishing different regimes of nonlinear propagation and determining the critical powers for self-focusing and mature filamentation of Gaussian and structured laser pulses in optical media.

Chromatin accessibility dynamics during cell fate reprogramming.

Genome architecture and chromatin dynamics govern the fate and identify of a cell. Recent advances in mapping chromatin landscapes offer valuable tools for the acquisition of accurate information regarding chromatin dynamics. Here we discuss recent findings linking chromatin dynamics to cell fate control. Specifically, chromatin undergoes a binary off/on switch during iPSC reprogramming, closing and opening loci occupied by somatic and pluripotency transcription factors, respectively. This logic of a binary off/on switch may also be operational in cell fate control during normal development and implies that further approaches could potentially be developed to direct cell fate changes both in vitro and in vivo.

ß-Glycosylations with 2-Deoxy-2-(2,4-dinitrobenzenesulfonyl)-amino-glucosyl/galactosyl Selenoglycosides: Assembly of Partially N-Acetylated ß-(1 → 6)-Oligoglucosaminosides.

An efficient protocol has been established for ß-glycosylations with 2-deoxy-2-(2,4-dinitrobenzenesulfonyl)amino (2dDNsNH)-glucopyranosyl/galactopyranosyl selenoglycosides using PhSeCl/AgOTf as an activating system. The reaction features highly ß-selective glycosylation with a wide range of alcohol acceptors that are either sterically hindered or poorly nucleophilic. Thioglycoside- and selenoglycoside-based alcohols prove to be viable nucleophiles, opening up new opportunities for one-pot construction of oligosaccharides. The power of this approach is highlighted by the efficient assembly of tri-, hexa-, and nonasaccharides composed of ß-(1 → 6)-glucosaminosyl residues based on one-pot preparation of a triglucosaminosyl thioglycoside with DNs, phthaloyl, and 2,2,2-trichloroethoxycarbonyl as the protecting groups of amino groups. These glycans are potential antigens for developing glycoconjugate vaccines against microbial infections.

The neurovascular couplings between electrophysiological and hemodynamic activities in anticipatory selective attention.

Selective attention is thought to involve target enhancement and distractor inhibition processes. Here, we recorded simultaneous electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) data from human adults when they were pre-cued by the visual field of coming target, distractor, or both of them. From the EEG data, we found alpha power relatively decreased contralaterally to the to-be-attended target, as reflected by the positive-going alpha modulation index. Late alpha power relatively increased contralaterally to the to-be-suppressed distractor, as reflected by the negative-going alpha modulation index. From the fNIRS data, we found enhancements of hemodynamic activity over the contralateral hemisphere in response to both the target and the distractor anticipation but within nonoverlapping posterior brain regions. More importantly, we described the specific neurovascular modulation between alpha power and oxygenated hemoglobin signal, which showed a positive coupling effect during target anticipation and a negative coupling effect during distractor anticipation. Such flexible neurovascular couplings between EEG oscillation and hemodynamic activity seem to play an essential role in the final behavioral outcomes. These results provide unique neurovascular evidence for the dissociation of the mechanisms of target enhancement and distractor inhibition. Individual behavioral differences can be related to individual differences in neurovascular coupling.

Chromatin accessibility illuminates single-cell regulatory dynamics of rice root tips.

BACKGROUND: Root development and function have central roles in plant adaptation to the environment. The modification of root traits has additionally been a major driver of crop performance since the green revolution; however, the molecular underpinnings and the regulatory programmes defining root development and response to environmental stress remain largely unknown. Single-cell reconstruction of gene regulatory programmes provides an important tool to understand the cellular phenotypic variation in complex tissues and their response to endogenous and environmental stimuli. While single-cell transcriptomes of several plant organs have been elucidated, the underlying chromatin landscapes associated with cell type-specific gene expression remain largely unexplored. RESULTS: To comprehensively delineate chromatin accessibility during root development of an important crop, we applied single-cell ATAC-seq (scATAC-seq) to 46,758 cells from rice root tips under normal and heat stress conditions. Our data revealed cell type-specific accessibility variance across most of the major cell types and allowed us to identify sets of transcription factors which associate with accessible chromatin regions (ACRs). Using root hair differentiation as a model, we demonstrate that chromatin and gene expression dynamics during cell type differentiation correlate in pseudotime analyses. In addition to developmental trajectories, we describe chromatin responses to heat and identify cell type-specific accessibility changes to this key environmental stimulus. CONCLUSIONS: We report chromatin landscapes during rice root development at single-cell resolution. Our work provides a framework for the integrative analysis of regulatory dynamics in this important crop organ at single-cell resolution.

Effects of environmental factors on avian communities in urban parks in small- to medium-sized city: a case study of Fuyang City, Anhui, China.

With a worldwide expansion of urbanization, the conservation of urban biodiversity is attracting growing attention; it is important to study the relationship between wildlife and urban green spaces. In this study, we selected 31 parks in the urban area of Fuyang City in the North China Plain. A total of 8795 individual birds from 69 species were recorded. The study found that (a) at the local level, tree diversity and heights are the most important factors contributing to each level of bird diversity, followed by the coverage of shrubs and herbs, and (b) at the landscape level, the proportion of woodland has a strong positive correlation with the multidimensional diversity of birds, followed by the patch diversity and percent of grassland. Our results showed that artificial greenland can effectively increase bird diversity. While considering urban planning and human well-being, the proportion of vegetation and landscape in urban parks should be properly planned, providing more habitats to enrich bird diversity.

Elongation of filamentation and enhancement of supercontinuum generation by a preformed air density hole.

The filamentation of the femtosecond laser pulse in air with a preformed density hole is studied numerically. The result shows that density-hole-induced defocusing effect can relieve the self-focusing of the pulse, and by changing the length of the density hole and relative delay time, the filamentation length, intensity, spectral energy density and broaden region can be effectively controlled. When a short density hole with millisecond delay time is introduced, a significant elongation of the filamentation and enhancement of supercontinuum intensity can be obtained. This study provides a new method to control filamentation by pulse sequence.

Influence of a pinhole diameter on the experimental determination of critical power for femtosecond filamentation in air.

Filamentation of intense femtosecond laser pulses in optical media has attracted great attention due to its various unique characteristics and potential applications. It is an important task to determine the critical power for the filamentation especially in many applications, which can be obtained by evaluating the transmitted pulse energy through a pinhole located in the filamentation region as a function of input laser energy. The pinhole diameter is very crucial to the measurement. However, there is no report on the experimental determination of critical power for filamentation in air by using the pinhole method and the influence of the pinhole diameter on the determination. In this paper, we numerically and experimentally investigate the influence of pinhole diameter on the determination of the filamentation critical power. The obtained critical power tends to a reasonable value as the decrease of the pinhole diameter, because the transmitted energy through the pinhole with a smaller diameter is more sensitive to the change of energy distribution in the beam cross section during the beginning process of filamentation. Under our experimental condition, the pinhole diameter as small as ∼50 µm is applicable to be used to determine the critical power for filamentation of femtosecond laser pulses in air.

Intense vector supercontinuum radiation from femtosecond filamentation.

Intense vector supercontinuum (SC) radiation with spatial polarization is obtained by using 800nm femtosecond vector laser beams in the air. The SC generated by azimuthally, radially, cylindrically polarized beams, and higher-order vector beams are investigated, respectively. The results show that the SC generated by vector beams is greatly enhanced compared to that by a Gaussian beam. The energy density of SC radiation reaches the order of 1µJ/nm in a bandwidth of 258 nm from 559 nm to 817 nm and 0.1 µJ/nm from 500 nm to 559 nm. Furthermore, by checking the polarization distribution of SC in different wavelengths from visible to near-infrared bands, we find that the SC maintains nearly the same polarization distribution as pump pulses. This work provides an effective and convenient way to generate powerful SC vector beams which may facilitate potential applications including optical communication, micro/nano-fabrication, and super-resolution microscopy.

Simultaneous spatial and temporal focusing optical vortex pulses for micromachining through optically transparent materials.

We introduce the optical vortex beam into simultaneous spatial and temporal focusing (SSTF) technique, and theoretically and experimentally demonstrate the local control of peak intensity distribution at the focus of a simultaneous spatiotemporally focused optical vortex (SSTF OV) beam. To avoid nonlinear self-focusing in the conventional focusing scheme, a spatiotemporally focused femtosecond laser vortex beam was employed to achieve doughnut-shaped ablation and high aspect ratio (∼28) microchannels on the back surface of 3 mm thick soda-lime glass and fused silica substrates.