The aberrant invasive capability of trophoblast cells is widely acknowledged as a primary mechanism underlying RSA. Recently, IGF2BP3 has been implicated in various cancers due to its influence on cellular invasion and migration. However, whether IGF2BP3 involve in the occurrence of RSA and the specific functions it assumes in the development of RSA remain elusive. In our study, we firstly collected villous tissues from RSA and those with normal pregnancies individuals to performed Protein sequencing and then detected the expression of IGF2BP3 through Western blot, qRT-PCR and immunohistochemistry. Secondly, we analyzed the single-cell data (GSE214607) to assess the expression of IGF2BP3 in invasive EVT trophoblasts. Thirdly, we utilized lentivirus technology to establish HTR-8/SVneo cell lines with stable IGF2BP3 knockdown and RNA-seq analysis was employed to investigate the GO functional pathway enrichment of IGF2BP3. Meanwhile, the effect of IGF2BP3 knockdown on trophoblast cells apoptosis, migration, and ferroptosis was evaluated through functional experiments. Additionally, LPS-induced abortion animal model was constructed to evaluate IGF2BP3 expression in placental tissues. A significant downregulation of IGF2BP3 was observed in the villous tissues of RSA patient, a finding corroborated by subsequent single cell sequencing results. Furthermore, it suggested that IGF2BP3 may be involved in the migration and apoptotic processes of trophoblast cells. Mechanistic research indicated that IGF2BP3 knockdown could compromise GPX4 mRNA stability, leading to the promotion of ferroptosis. Finally, our investigation observed the down-regulation of IGF2BP3 expression in placental villous tissues of an LPS-induced abortion animal model. Our findings revealed that IGF2BP3 was downregulated in the villous tissues of RSA patients. Mechanically, down-regulation of IGF2BP3 may induce RSA by promoting GPX4-mediated ferroptosis and inhibiting trophoblast invasion and migration. Our study may provide new targets and research directions for the pathogenesis of RSA.

Nouns and verbs are fundamental grammatical building blocks of languages. A key question is whether and where the noun-verb division was represented in the brain. Previous studies mainly used univariate analyses to examine this issue. However, the interpretation of activated brain regions in univariate analyses may be confounded with general cognitive processing and/or confounding variables. We addressed these limitations by using partial representation similarity analysis (RSA) of Chinese nouns and verbs with different levels of imageability. Participants were asked to complete the 1-back grammatical class probe (GCP; an explicit measure) and the 1-back word probe (WP; an implicit measure) tasks while undergoing functional magnetic resonance imaging. RSA results showed that the activation pattern in the left posterior middle temporal gyrus (LpMTG) was significantly correlated with the grammatical class representational dissimilarity matrix in the GCP task after eliminating the potential confounding variables. Moreover, the LpMTG did not overlap with the frontal-parietal regions that were activated by verbs vs. nouns or the task effect (CRP vs. WP) in univariate analyses. These results highlight the role of LpMTG in distinguishing nouns from verbs rather than general cognitive processing.

Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces.

BACKGROUND: Clinically, recurrent spontaneous abortion (RSA) is a pregnancy illness that is difficult to treat. Impaired decidualization is a documented cause of RSA, but the etiology and mechanism are still unknown. cAMP-responsive element binding protein 5 (CREB5) is a member of the ATF/CREB family. CREB5 has been reported to be related to pathological pregnancy, but there are few related studies on this topic in patients with RSA, and the underlying mechanism is unclear.
METHODS: We collected decidual tissues from RSA patients and healthy pregnant women to measure the expression level of CREB5, PRL, IGFBP1, ATG5, LC3B, and SQSTM/p62. Then, the changes in CREB5 expression and autophagy levels were measured in human endometrial stromal cells (hESCs) during decidualization. The expression levels of PRL and IGFBP1 were tested in sh-CREB5/ov-CREB5 hESCs after decidualization induction, and the autophagy level in sh-CREB5/ov-CREB5 hESCs was measured without decidualization induction. The decidualization ability of sh-CREB5 and ov-CREB5 hESCs treated with an autophagy inducer or inhibitor was measured. To investigate the effect of CREB5 in hESCs on the invasion and migration of HTR8/SVneo cells, we performed a coculture experiment. Finally, we examined the expression of CREB5 and autophagy key proteins in mouse decidual tissues by constructing an abortion mouse model.
RESULTS: In our study, we found that the expression of CREB5 was unusually elevated in the uterine decidua of RSA patients, but the expression of PRL, IGFBP1, and autophagy were decreased. During the decidualization of hESCs, the expression of CREB5 gradually decreases in a time-dependent manner with increasing autophagy. Moreover, by knocking down or overexpressing CREB5 in hESCs, it was found that CREB5 can impair decidualization and reduce autophagy in hESCs. Furthermore, the damage caused by CREB5 in terms of decidualization can be reversed by the addition of an autophagy inducer (rapamycin). In addition, CREB5 can increase the secretion of proteins (IL-1β and TGF-β1) in hESCs to inhibit trophoblast invasion and migration.
CONCLUSIONS: Our data support the supposition that CREB5 disturbs the decidualization of endometrial stromal cells and interactions at the maternal-fetal interface by inhibiting autophagy and that its abnormal upregulation and dysfunction may lead to RSA. It may function as a diagnostic and therapeutic target for RSA. Similarly, we found that in the spontaneous abortion mouse model, the expression of CREB5 in the decidual tissue of the abortion group was significantly increased, and autophagy was decreased.

OBJECTIVE: As a member of the C19MC family, miR-526b-5p is mainly expressed in the placental tissue and is a well-known tumor suppressor microRNA. However, its effect on the function of trophoblasts and its role in the development of recurrent spontaneous abortion (RSA) remains unclear.
METHODS: Transcriptome sequencing, quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, 5-ethynyl-2\'-deoxyuridine (Edu) proliferation analysis, cell counting kit-8 (CCK8) assay, Transwell assays, and wound healing were used to detect the proliferation, migration, and invasion capacity of trophoblasts. Target genes of miR-526b-5p were obtained by the dual luciferase reporter system. The promoter-reporter system and ChIP-qPCR were used to prove that c-Myc positively regulated the expression of Foxp1 RESULTS: The miR-526b-5p levels were significantly higher in patients with RSA than in controls. High expression of miR-526b-5p inhibited the proliferation, migration, and invasion of trophoblast cell line. By contrast, low expression of miR-526b-5p promoted the proliferation and migration of trophoblast cell line. Target genes of miR-526b-5p were c-Myc and Foxp1. c-Myc positively regulated the expression of Foxp1 by binding to the Foxp1 promoter location -146/-135. Finally, miR-526b-5p impeded the proliferation, migration, and invasion of trophoblasts by negatively regulating c-Myc by rescue experiments.
CONCLUSIONS: Thus, miR-526b-5p affected the proliferation, migration, and invasion of trophoblasts by targeting c-Myc and Foxp1. Low expression of c-Myc further deactivated the positive transcriptional regulation of c-Myc on Foxp1, which may be the mechanism of RSA. This study provides potential therapeutic targets and clues for the diagnosis and treatment of RSA.

In an ultimatum game, the responder must decide between pursuing self-interest and insisting on fairness, and these choices are affected by the intentions of the proposer. However, the time course of this social decision-making process is unclear. Representational similarity analysis (RSA) is a useful technique for linking brain activity with rich behavioral data sets. In this study, electroencephalography (EEG) was used to measure the time course of neural responses to proposed allocation schemes with different intentions. Twenty-eight participants played an ultimatum game as responders. They had to choose between accepting and rejecting the fair or unfair money allocation schemes of proposers. The schemes were offered based on the proposer\'s selfish intention (monetary gain), altruistic intention (donation to charity), or ambiguous intention (unknown to the responder). We used a spatiotemporal RSA and inter-subject RSA (IS-RSA) to explore the connections between event-related potentials (ERPs) after offer presentation and intention presentation with four types of behavioral data (acceptance, response time, fairness ratings, and pleasantness ratings). The spatiotemporal RSA results revealed that only response time variation was linked with the difference in ERPs at 432-592 ms after offer presentation on the posterior parietal and prefrontal regions. Meanwhile, the IS-RSA results found a significant association between inter-individual differences in response time and differences in ERP activity at 596-812 ms after the presentation of ambiguous intention, particularly in the prefrontal region. This study expands the intention-based reciprocal model to the third-party context and demonstrates that brain activity can represent response time differences in social decision-making.

The dynamics of parent-infant physiology are essential for understanding how biological substrates of emotion regulation are organized during infancy. Although parent-infant physiological processes are dyadic in nature, research is limited in understanding how one person\'s physiological responses predict one\'s own and as well as the other person\'s responses in the subsequent moment. In this study, we examined mother-infant respiratory sinus arrhythmia (RSA) dynamics during the Still-Face Paradigm (SFP) among 106 mothers (Mage  = 29.54) and their 7-month-old infants (55 males). Given mothers\' role in shaping dyadic interactions with their infant, we also tested how mothers\' self-reported emotion dysregulation (measured via the Difficulties in Emotion Regulation Scale) associated with these dynamics. Results showed that both mothers\' and infants\' RSA tended to return to their respective homeostatic points (i.e., exhibited return strength) during each SFP episode, indicating stability in RSA for mother-infant dyads. Significant shifts in mother and infant RSA return strength were observed across SFP episodes, highlighting the role of contextual demands on each individual\'s physiological dynamics. Mother-infant RSA dynamics varied as a function of maternal self-reported emotion dysregulation. Specifically, RSA levels of infants with more dysregulated mothers had a weaker tendency to return to homeostasis during the Reunion episode and were less affected by their mothers\' RSA during the Still-Face and Reunion episodes of the SFP, suggesting a less effective coregulatory influence. Our findings have implications for the intergenerational transmission of emotion dysregulation via mother-infant physiological dynamics.

Although the interaction between P and Zn has long been recognized in plants, the physiological and molecular mechanisms underlying P and Zn interactions are poorly understood. We show here that P supply decreases the Zn concentration in maize shoots and roots. Compared to +P + Zn (addition of both P and Zn), +P-Zn reduced and -P-Zn increased the total length of 1° lateral roots (LRs). Under +P + Zn, both P and Zn concentrations were lower in the sl1 mutant roots than in wild-type (WT) maize roots, and P accumulation did not reduce the Zn concentration in ll1 mutant roots. Transcriptome profiling showed that the auxin signaling pathway contributed to P-mediated Zn homeostasis in maize. Auxin production and distribution were altered by changes in P and Zn supply. Cytosolic Zn co-localized with auxin accumulation under +P + Zn. Exogenous application of 1-NAA and L-Kyn altered the P-mediated root system architecture (RSA) under Zn deficiency. -P-Zn repressed the expression of miR167. Overexpression of ZmMIR167b increased the lengths of 1° LRs and the concentrations of P and Zn in maize. These results indicate that auxin-dependent RSA is important for P-mediated Zn homeostasis in maize.HighlightAuxin-dependent RSA is important for P-mediated Zn homeostasis in maize.

We evaluated root system architecture (RSA) of a set of 58 historical spring wheat cultivars from Pakistan representing 105 years of selection breeding. The evaluations were carried out under control and water-limited conditions using a high-throughput phenotyping system coupled with RhizoVision Explorer software. The cultivars were classified into three groups based on release year as cultivars released pre-1965, released between 1965 and 2000, and cultivars released post-2000. Under water-limited conditions a decline in 20 out of 25 RSA component traits was observed in pre-1965 cultivars group. Whereas cultivars released after the 1965, so-called green revolution period, showed a decline in 17 traits with significant increments in root length, depth, and steep angle frequency which are important root traits for resource-uptake under water-limited conditions. Similarly, cultivars released after 2000 indicated an increase in the number of roots, depth, diameter, surface area, and steep angle frequency. The coefficient of correlation analysis showed a positive correlation between root depth and yield-related traits under water-limited conditions. We also investigated the effects of green-revolution genes (Rht1) and some phenology-related genes such as DRO1, TaMOR, TaLTPs, TaSus-2B on RSA and identified significant associations of these genes with important root traits. There was strong selection pressure on DRO1 gene in cultivated wheat indicating the allele fixed in modern wheat cultivars is different from landraces. The expression of DRO1, and TaMOR were retrieved from an RNAseq experiment, and results were validated using qRT-PCR. The highest expression of DRO1 and TaMOR was found in Chakwal-50, a rainfed cultivar released in 2008, and MaxiPak-65 released in 1965. We conclude that there is a positive historic change in RSA after 1965 that might be attributed to genetic factors associated with favored RSA traits. Furthermore, we suggest root depth and steep angle as promising traits to withstand water-limited environments and may have implications in selection for breeding.

The establishment and maintenance of pregnancy are involved in maternal-fetal immune tolerance whose imbalance can lead to recurrent spontaneous abortion (RSA). RSA is defined as two or more clinically recognized pregnancy losses within 20-24 weeks of gestation with the same partner, including embryonic and fetal losses. However, approximately half of RSA cases are idiopathic, which may be related to immune aberrations. T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is an inhibitory checkpoint protein that plays a critical role in immune tolerance. Several studies have reported that Tim-3 expression in immune cells is important for maintaining maternal-fetal immune tolerance and that the abnormal expression of Tim-3 may be associated with RSA. To further understand the etiology and pathogenesis of RSA and inspire novel strategies for its diagnosis and treatment, we reviewed the research progress on the Tim-3-induced regulation of natural killer cells, T cells, macrophages, dendritic cells, and myeloid-derived suppressor cells in maternal-fetal immune tolerance and RSA.