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Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming.

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Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/ß-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/ß-catenin signaling and cell type commitment in somatic development.

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This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

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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.

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In this study, phase change materials (PCMs) were innovatively incorporated into hybrid fiber concrete. The properties of PCMs, which absorb and release heat during phase transitions, enable the concrete to actively respond to complex and varying temperature environments. This integration reduces the internal temperature differentials within the concrete, thereby preventing temperature-induced cracks in deep wellbore structures. Through the temperature control model test of the frozen shaft wall, it can be seen that the hybrid fiber phase change concrete (HFPCC) significantly reduces the internal temperature difference, and the maximum temperature difference along the radial direction is 35.84% lower than that of benchmark concrete (BC). The numerical simulation results indicate that a moderate phase transition temperature should be selected in engineering. The phase change temperature should not be close to the ambient temperature and peak temperature. The peak temperature can be reduced by 9.32% and the maximum radial temperature difference can be reduced by 30.89% by selecting an appropriate phase change temperature. The peak temperature and radial maximum temperature difference are both proportional to the latent heat of phase change. The temperature control performance of phase change concrete can be further improved by increasing the latent heat of phase change materials.

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In Northwest China, the highway infrastructure often faces challenges due to the widespread presence of subgrade soil. This soil undergoes significant changes in performance under cyclic loading and freeze-thaw cycles. To effectively design and construct highways in these regions, it is crucial to understand the impact of various factors on the deformation characteristics and mechanical properties of subgrade soil. This study aims to investigate the influence of freeze-thaw cycles, water content, confining pressure, and loading rate on the deformation behavior and mechanical properties of subgrade soil under cyclic loading conditions. Experimental tests were conducted to analyze the deformation characteristics and mechanical properties of the subgrade soil. The test results revealed the following: 1) Dynamic loading leads to a noticeable decrease in the strength of subgrade soil, resulting in a softening effect on the stress-strain curve. The cumulative strain of the soil is positively correlated with the number of freeze-thaw cycles and water content, while negatively correlated with confining pressure. The final cumulative strain remains below 1%. 2) The failure stress of subgrade soil decreases exponentially with an increase in freeze-thaw cycles, dropping from 224.52 kPa to 196.76 kPa. 3) An increase in water content linearly decreases the failure stress of subgrade soil, ranging from 377.1 kPa to 151.5 kPa. 4) Confining pressure exhibits a linearly increasing relationship with the failure stress of subgrade soil, ranging from 151.6 kPa to 274.5 kPa. 5) The failure stress of subgrade soil demonstrates a linear increase with the loading rate, ranging from 200.46 kPa to 210.62 kPa. These findings provide valuable insights for the design and construction of highways in seasonal frozen areas. They also offer guidance for preventing and mitigating subgrade freeze-thaw issues in the future.

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Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines.

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Nasal tamponade is a commonly employed and highly effective treatment method for preventing nasal bleeding. However, the current nasal packing hemostatic materials exhibit some limitations, such as low hemostatic efficiency, the potential for causing secondary injury when removed from the nasal cavity, limited intelligence in their design, and an inability to promote the healing of nasal mucosa wounds. Herein, we report the fabrication of a smart cellulose aerogel through the covalent cross-linking of carboxymethyl cellulose (CMC) macromolecules, while incorporating one-dimensional cellulose nanofibers (CNF) and two-dimensional MXene as reinforcing network scaffolds and conductive fillers. The abundant hydrogen and ether bonds in aerogels make them possess high elasticity in both dry and wet states, which can be compressed 100 times at 90 % deformation with a stress loss of <10 % under water. The highly elastic aerogels can be filled into the narrow nasal passages, pressuring the capillaries and reducing the amount of bleeding. Moreover, the strong interface between aerogels and blood can promote red blood cell aggregation, platelet adhesion and activation, activate intrinsic coagulation pathway and accelerate blood coagulation, resulting in excellent hemostatic ability. Furthermore, the aerogels exhibit excellent hemocompatibility and cytocompatibility, making them suitable for wound healing and capable of fully healing wounds within 15 days. Notably, the presence of MXene causes the aerogels to form a conductive network when exposed to blood, enabling them to perform real-time hemostatic monitoring without removing the dressing. This innovative biomedical aerogel, prepared from natural materials, shows excellent potential for applications in rapid nasal hemostasis.

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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.

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Carbon-fixing bacterial communities are essential drivers of carbon fixation in estuarine ecosystems that critically affect the global carbon cycle. This study compared the abundances of the Calvin cycle functional genes cbbL and cbbM and Reductive tricarboxylic acid cycle gene aclB, as well as compared carbon-fixing bacterial community features in the two estuaries, predicted potential ecological functions of carbon-fixation bacteria, and analyzed their symbiosis strategies in two estuaries having different geographical distributions. Gammaproteobacteria was the dominant carbon-fixing bacterial community in the two estuaries. However, a higher number of Alphaproteobacteria were noted in the Liaohe Estuary, and a higher number of Betaproteobacteria were found in the Yalujiang Estuary. The carbon-fixing functional gene levels exhibited the order of aclB > cbbL > cbbM, and significant effects of Cu, Pb, and petroleum were observed (p < 0.05). Nitrogen-associated nutrient levels are major environmental factors that affect carbon-fixing bacterial community distribution patterns. Spatial factors significantly affected cbbL carbon-fixing functional bacterial community structure more than environmental factors. With the increase in offshore distance, the microbial-led processes of methylotrophy and nitrogen fixation gradually weakened, but a gradual strengthening of methanotrophy and nitrification was observed. Symbiotic network analysis of the microorganisms mediating these ecological processes revealed that the carbon-fixing bacterial community in these two estuaries had a non-random symbiotic pattern, and microbial communities from the same module were strongly linked among the carbon, nitrogen, and sulfur cycle. These findings could advance the understanding of carbon fixation in estuarine ecosystems.

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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.

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Focusing attention in visual working memory (vWM) depends on the ability to filter distractors and expand the scope of targets. Although many properties of attention processes in vWM have been well documented, it remains unclear how the mechanisms of neurovascular coupling (NVC) function during attention processes in vWM. Here, we show simultaneous multimodal data that reveal the similar temporal and spatial features of attention processes during vWM. These similarities lead to common NVC outcomes across individuals. When filtering out distractors, the electroencephalography (EEG)-informed NVC displayed broader engagement across the frontoparietal network. A negative correlation may exist between behavioral metrics and EEG-informed NVC strength related to attention control. On a dynamic basis, NVC features exhibited higher discriminatory power in predicting behavior than other features alone. These results underscore how multimodal approaches can advance our understanding of the role of attention in vWM, and how NVC fluctuations are associated with actual behavior.

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We perform numerical simulations to investigate the nonlinear propagation dynamics of femtosecond Gaussian and vortex beams in fused silica. By analyzing the extent of spectral broadening, we are able to distinguish between the linear, self-focusing, and filamentation regimes. Additionally, the maximum intensity and fluence distribution within the cross-section of the vortex beams are analyzed for different incident laser energies. The results demonstrate a direct correlation between the spectral broadening and the peak intensity of the femtosecond laser pulse. As a result, this provides a theoretical foundation for distinguishing different propagation regimes, and determining critical powers for self-focusing and filamentation of both femtosecond Gaussian and structured beams.

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The favorable benefit-risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody-drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents.

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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.

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Chromite ore processing residue (COPR) is a hazardous waste because of leachable chromium, especially Cr(vi). Therefore, ascorbic acid (AA) and blast furnace slag (BFS) have been used to detoxify and solidify COPR. On this basis, environmental stability experiments with high temperature and freeze-thaw cycles were carried out to explore the stability performance of a solidified body with 40% COPR. The environmental stability performance was analyzed through changes in edge length, mass loss, compressive strength development, and leaching concentration of Cr(vi). The result indicated that the high-temperature environment had much more effect on the solidified body than the freeze-thaw cycle environment in these four aspects: after being maintained at 900 °C for 2 h, the compressive strength of the solidified bodies reached its minimum value (35.76 MPa). However, in the freeze-thaw cycle experiments, the compressive strength of the solidified bodies consistently remained above 80 MPa, and the leaching of hexavalent chromium was below the limit (5 mg L-1). In addition, X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FTIR) analysis verified that COPR was effectively solidified through physical and chemical means. Moreover, high temperature changes the molecular structure of the solidified body, thus reducing the compressive strength and curing ability of the solidified body, while the freeze-thaw cycle experiment has little effect on it.

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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.

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Identifying the potential factors associated with the impact of long-term drip irrigation (DI) on soil ecosystems is essential for responding to the environmental changes induced by extensive application of DI technology in arid regions. Herein, we examined the effects of the length of time that DI lasts in years (NDI) on soil bacterial diversity as well as the soil bacterial community assembly process and the factors influencing it. The results showed that long-term DI substantially reduced soil salinity and increased soil bacterial diversity while affecting the soil bacterial community structure distinctly. Null model results showed that the soil bacterial community assembly transitioned from stochastic processes to deterministic processes, as NDI increased. Homogeneous selection, a deterministic process, emerged as the dominant process when NDI exceeded 15 years. Both random forest and structural equation models showed that soil salinity was the primary factor affecting the bacterial community assembly process. In summary, this study suggested that soil bacteria respond differently to long-term DI and depends on the NDI, influencing the soil bacterial community assembly process under long-term DI.

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Permanent structural changes in pure metals that are caused by plastic activity are normally irreparable after unloading. Because of the lack of experimental evidence, it is unclear whether the plastic activity can be repaired as the size of the pure metals decreases to several nanometers; it is also unclear how the metals accommodate the plastic deformation. In this study, the in situ atomic-scale loading and unloading of ∼2 nm Ag nanocrystals was investigated, and three modes of plastic deformation were observed: (i) the phase transition from the face-centered cubic (fcc) phase to the hexagonal close-packed (hcp) phase, (ii) stacking faults, and (iii) deformation twin nucleation. We show that all three modes resulted in structural changes that were reparable, and their generation and restoration during loading and unloading were observed in situ. We discovered that the deformation modes of nanosized metals can be predicted from the ratio of the energy barriers of the fcc-hcp phase transition (ΔγH) and the deformation twin nucleation (ΔγT), which differ from those of the theoretical modes of relatively large-sized metals. The proposed ΔγH/ΔγT criterion provides insights into the deformation mechanism of nanometals.

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BACKGROUND: c-Jun is a proto-oncogene functioning as a transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role in early embryonic development remains unknown. RESULTS: Here, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naïve state. c-Jun is induced during the naive to primed transition, and it works to stabilize the chromatin structure and inhibit the reverse transition. Loss of c-Jun has surprisingly little effect on the naïve to primed transition, and no phenotypic effect on primed cells, however, in primed cells the loss of c-Jun leads to a failure to correctly close naïve-specific enhancers. When the primed cells are induced to reprogram to a naïve state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient. CONCLUSIONS: The results of this study indicate that c-Jun can function as a chromatin stabilizer in primed EpiSCs, to maintain the epigenetic cell type state and act as a one-way valve for cell fate conversions.