Strongly Localized Moiré Exciton in Twisted Homobilayers.

Artificially molding exciton flux is the cornerstone for developing promising excitonic devices. In the emerging hetero/homobilayers, the spatial separated charges prolong exciton lifetimes and create out-plane dipoles, facilitating electrically control exciton flux on a large scale, and the nanoscale periodic moiré potentials arising from twist-angle or/and lattice mismatch can substantially alter exciton dynamics, which are mainly proved in the heterostructures. However, the spatially indirect excitons dynamics in homobilayers without lattice mismatch remain elusive. Here the nonequilibrium dynamics of indirect exciton in homobilayers are systematically investigated. The homobilayers with slightly twist-angle can induce a deep moiré potential (>50 meV) in the energy landscape of indirect excitons, resulting in a strongly localized moiré excitons insulating the transport dynamics from phonons and disorder. These findings provide insights into the exciton dynamics and many-body physics in moiré superlattices modulated energy landscape, with implications for designing excitonic devices operating at room temperature.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Prediction of phase transition and time-varying dynamics of the (2+1)-dimensional Boussinesq equation by parameter-integrated physics-informed neural networks with phase domain decomposition.

A meaningful topic that needs to be explored in the field of nonlinear waves is whether a neural network can reveal the phase transition of different types of waves and novel dynamical properties. In this paper, a physics-informed neural network (PINN) with parameters is used to explore the phase transition and time-varying dynamics of nonlinear waves of the (2+1)-dimensional Boussinesq equation describing the propagation of gravity waves on the surface of water. We embed the physical parameters into the neural network for this purpose. Via such algorithm, we find the exact boundary of the phase transition that distinguishes the periodic lump chain and transformed wave, and the inexact boundaries of the phase transition for various transformed waves are detected through PINNs with phase domain decomposition. In particular, based only on the simple soliton solution, we discover types of nonlinear waves as well as their interesting time-varying properties for the (2+1)-dimensional Boussinesq equation. We further investigate the stability by adding noise to the initial data. Finally, we perform the parameters discovery of the equation in the case of data with and without noise, respectively. Our paper introduces deep learning into the study of the phase transition of nonlinear waves and paves the way for intelligent explorations of the unknown properties of waves by means of the PINN technique with a simple solution and small data set.

Distinct brain state dynamics of native and second language processing during narrative listening in late bilinguals.

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.

Anomalous transmission and Anderson localization for alternating propagated and evanescent waves at the deep-subwavelength scale.

Deep-subwavelength features have a minimal impact on wave transport in all dielectric systems; thus the homogenization approach was commonly adopted. Recently, the breakdown of effective medium theory (EMT) for the incident wave near the total reflection (TR) angle was demonstrated in a deep-subwavelength dielectric multilayer. Additionally, anomalous transmission was reported at angles exceeding the TR angle when introducing disorder and was attributed to Anderson localization. Here we firstly demonstrated that the alleged anomalous transmission also occurs in the disorder-free case, illustrating that attributing anomalous transmission to Anderson localization deserves a more in-depth study. To clarify the underlying physics of this asserted anomalous transmission, Anderson localization and broken EMT, the incident angle dependent reflectivity and modes for ordered and disordered deep-subwavelength multilayers were investigated systematically. Actually, the EMT is still convincing and the anomalous transmission is reasonable after a simple correction. However, the anomalous transmission is more accessible and the permittivity correction is more imperative in the disordered system due to the Anderson localization. These findings can be expanded to other wave systems such as acoustic waves and matter waves, providing insight into EMT and deepening our understanding of the intriguing transport phenomena in deep subwavelength systems.

Extended one generation reproductive toxicity study and effect on gut flora of genetically modified rice rich in ß-carotene in wistar rats.

To evaluate the reproductive toxicity of gene modified rice generated by introducing phytoene synthase (Psy) and bacterial phytoene desaturase (CrtI) from maize and Erwinia uredovora, Wistar rats were allocated into 3 groups and fed with Psy and CrtI gene modified rice mixture diet (GM group), non-gene modified rice mixture diet (non-GM group), and AIN-93 diet (Blank control group) from parental generation (F0) to the offsprings (F1). GM rice, Heijinmi (HJM) and Non-GM rice, Heishuai (HS), were both formulated into diets at ratios of 73.5% and 75.5% according to the AIN93 diet for rodent animals, respectively. Relative to the non-GM group, no biologically relevant differences were observed in GM group rats concerning reproductive performance such as fertility rate, gestation rate, mean duration, hormone level, and reproductive organ pathology. The developmental parameters results were not significantly different from the non-GM group such as body weight, food consumption, developmental neurotoxicity, behavior, hematology, and serum chemistry. In terms of immunotoxicity, the IgG indicators of offspring from the GM group improved in contrast with the non-GM group. Additional gut flora analysis of F0 generation rats resulted as that the treatment elicited an increased gut microflora diversity of F0 rats. And no horizontal gene transfer of Psy and CrtI genes in rats fed a GM rice HJM diet. In conclusion, we found no adverse effects related to GM rice in the extended one-generation reproductive toxicity study, indicating that GM rice is a safe alternative for its counterpart rice regarding reproductive toxicity.

Spatial distribution of floating population in Beijing, Tianjin and Hebei Region and its correlations with synergistic development.

Utilizing statistical information from the Seventh National Population Census, statistical yearbook and sampling dynamic survey data, this study examines the distribution characteristics of the floating population in Beijing, Tianjin and Hebei Region as well as the growth trend of the floating population in each region. It also makes assessments using floating population concentration and The Moran Index Computing Methods. According to the study, the spatial distribution of the floating population has a clear clustering pattern in Beijing, Tianjin and Hebei region. Beijing, Tianjin and Hebei region's mobile population growth patterns differ substantially, and the region's inflow population is mostly made up of migrant inhabitants of domestic provinces and inflow of people from nearby regions. Most of the mobile population resides in Beijing and Tianjin, whereas the outflow of people originates in Hebei province. The diffusion impact and the spatial features of the floating population in the Beijing, Tianjin and Hebei area have a constant, positive association, according to the timeline between 2014 and 2020.

Functional preference of the left inferior parietal lobule to second language reading.

Additional neural substance for reading in a second language has been reported by prior studies. However, to date, there has been little investigation into whether and how the brain's adaptation to a second language is induced by specific linguistic tasks or is a general effect during reading in a new language. To address this issue, our study investigated Chinese children learning English as a second language by combining cross-sectional and longitudinal Functional Magnetic Resonance Imaging (fMRI) studies. We compared brain activation across four reading tasks, orthographic tasks and phonological tasks in Chinese (the first language, L1) and English (the second language, L2). By comparing the activation pattern across languages, we observed greater activation in the left inferior parietal lobule (LIPL) in English compared to Chinese, suggesting a functional preference of the LIPL to L2. In addition, greater correlation between LIPL-related FC and L2 was mainly observed in the phonological task, indicating that LIPL could be associated with phonological processing. Moreover, a proportion of the children were enrolled in an 8-week phonological-based reading-training program. We observed significant functional plasticity of the LIPL elicited by this training program only in the English phonological task and not in the orthographic task, further substantiating that the additional requirements of the LIPL in L2 are mainly associated with phonological processing. The findings provide new insights into understanding the functional contribution of the LIPL to reading in a second language.

Exogenous melatonin mediates radish (Raphanus sativus) and Alternaria brassicae interaction in a dose-dependent manner.

Radish (Raphanus sativus L.) is an economically important vegetable worldwide, but its sustainable production and breeding are highly threatened by blight disease caused by Alternaria brassicae. Melatonin is an important growth regulator that can influence physiological activities in both plants and microbes and stimulate biotic stress resistance in plants. In this study, 0-1500 µM melatonin was exogenously applied to healthy radish seedlings, in vitro incubated A. brassicae, and diseased radish seedlings to determine the effects of melatonin on host, pathogen, and host-pathogen interaction. At sufficient concentrations (0-500 µM), melatonin enhanced growth and immunity of healthy radish seedlings by improving the function of organelles and promoting the biosynthesis of antioxidant enzymes, chitin, organic acid, and defense proteins. Interestingly, melatonin also improved colony growth, development, and virulence of A. brassicae. A strong dosage-dependent effect of melatonin was observed: 50-500 µM promoted host and pathogen vitality and resistance (500 µM was optimal) and 1500 µM inhibited these processes. Significantly less blight was observed on diseased seedlings treated with 500 µM melatonin, indicating that melatonin more strongly enhanced the growth and immunity of radish than it promoted the development and virulence of A. brassicae at this treatment concentration. These effects of MT were mediated by transcriptional changes of key genes as identified by RNA-seq, Dual RNA-seq, and qRT-PCR. The results from this work provide a theoretical basis for the application of melatonin to protect vegetable crops against pathogens.

Organic Semiconductor Nanosheets for Sulfite Detecting Based on Activation of Sulfite and a Synergetic Chemiluminescence Resonance Energy Transfer Process in a Mild System of Fe2+-SO32.

Sulfur dioxide (SO2) as one kind of air pollution not only causes extreme environmental pollution but also negatively affects human health. Chemiluminescence (CL) methods applied for sulfite analysis with high selectivity based on activating sulfite with oxidants are always implemented in acid media with a high background rise. In this work, we proposed to develop a mild CL system of Fe2+-SO32- to detect sulfite under neutral conditions and provide in situ CL spectral data for deeply studying the CL mechanism of Fe2+-SO32-. Herein, we first synthesized one type of water-soluble supramolecular nanosheets, APDI NSs, which had a strong oxidation potential (+2.9 V) due to a π-conjugated system for activation of sulfite to enhance the generation of SO3̇- and other active radicals, and strong a CL signal from the APDI NSs-Fe2+-SO32- system was generated. By studying the CL mechanism under acidic and neutral conditions, a new CL reaction pathway (path-1) and a key intermediate, S2O42-, from the reaction of Fe2+ and SO32- were found. The CL signal was emitted by SO2* after oxidation of S2O42- by strong oxidants like SO4•- and further amplified by APDI NSs through the CL resonance energy transfer (CRET) process. Based on the APDI NSs-Fe2+-SO32- system under neutral conditions, a CL method for detecting SO32- was established. The detection limit was 2.7 × 10-8 M (S/N = 3), and the recovery rates in spiked water samples were in the range of 87%-101%. This study strengthens the understanding of the CL reaction process of the Fe2+-SO32- system and provides a mild sulfite sensing platform for environmental samples.

The line rogue wave solutions of the nonlocal Davey-Stewartson I equation with PT symmetry based on the improved physics-informed neural network.

In the paper, we employ an improved physics-informed neural network (PINN) algorithm to investigate the data-driven nonlinear wave solutions to the nonlocal Davey-Stewartson (DS) I equation with parity-time (PT) symmetry, including the line breather, kink-shaped and W-shaped line rogue wave solutions. Both the PT symmetry and model are introduced into the loss function to strengthen the physical constraint. In addition, since the nonlocal DS I equation is a high-dimensional coupled system, this leads to an increase in the number of output results. The PT symmetry also needs to be learned that is not given in advance, which increases challenges in computing for multi-output neural networks. To address these problems, our objective is to assign various levels of weight to different items in the loss function. The experimental results show that the improved algorithm has better prediction accuracy to a certain extent compared with the original PINN algorithm. This approach is feasible to investigate complex nonlinear waves in a high-dimensional model with PT symmetry.

Noise properties of contactless integrated photonic probes on silicon waveguides.

Contactless integrated photonic probes (CLIPPs) have been used as on-chip power monitors with minimum perturbations to optical modes. In this work, we present the experimental measurements and analysis of the noise properties of these types of devices integrated with silicon waveguides. We focus on the study of how circuitry parameters, including the gain of the trans-impedance amplifier, lock-in bandwidth, and amplitude and frequency of the bias voltage, affect the noise properties. Finally, we establish a circuit model and use the Simulation Program with Integrated Circuit Emphasis to model and simulate the noise properties of these devices. Our analysis shows that the thermal noise of the CLIPPs and electrical noise of the trans-impedance amplifier are the dominant sources of noise.

Interactions between ultrasonographic cervical length and placenta accreta spectrum on severe postpartum hemorrhage in women with placenta previa.

OBJECTIVE: To explore the interactions between cervical length (CL) and placenta accreta spectrum (PAS) on severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: A retrospective case-control study was conducted at four medical centers in China, and 588 patients with placenta previa were included. The logistic regression analysis and restricted cubic splines (RCS) were used to evaluate the association between CL and SPPH. Furthermore, the joint effect of CL and PAS on SPPH was assessed, and the additive and multiplicative interactions were calculated. RESULTS: After adjusting for potential confounders, the negative linear dose-response relationship was confirmed by RCS, and the change of odds ratio (OR) was more significant when CL was 2.5 cm or less. The risk of SPPH was significantly higher when CL of 2.5 cm or less co-existed with placenta increta/percreta than when CL of 2.5 cm less, or placenta increta/percreta existed alone (adjusted OR [aOR]CL ≤2.5cm&placenta accreta/non-PAS 3.40, 95% confidence interval [CI] 1.37-8.45; aORplacenta increta/percreta&CL >2.5cm 4.75, 95% CI 3.03-7.47; aORCL ≤2.5cm&placenta increta/percreta 14.51, 95% CI 6.08-34.64), and there might be additive interaction between CL and placenta increta/percreta on SPPH (attributable proportion due to interaction 50.7%, 95% CI 6.1%-95.3%). CONCLUSION: If CL was routinely performed during PAS evaluation, the increased OR of short CL and PAS could allow better patient preparation through counseling.

5-azacytidine inhibits Sox2 promoter methylation during the induction of Thy-1+Lin- cells into hepatocytes.

OBJECTIVE: To investigate the changes and functions of Sox2 gene expression and promoter methylation during induced differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocytes (HCs). METHODS: Rat bone marrow Thy-1+Lin- cells were prepared and divided into control group (directed induction of differentiation into HCs) and experimental group (5-azacytidine intervention induced differentiation). The mRNA expression levels of ALB and Sox2 were detected by fluorescence quantitative polymerase chain reaction (PCR), and the Sox2 gene promoter methylation level was determined by Bisulfite sequencing PCR (BSP). RESULTS: Sox mRNA expression level was significantly increased in experimental group compared to the control group at 0, 7, and 14 days, respectively (all P<0.05). The Sox2 promoter methylation level was gradually increased after 0, 7 and 14 days induction in both groups, accompanied by an increase in methylated loci (all P<0.05). Statistical significance was present in CpG methylated loci between groups (all P<0.05). CONCLUSIONS: The expression of Sox2 gene increased first and then decreased in the process of inducing rat BMSCs into stem cells, and the methylation level of CpG loci in the promoter region changed dynamically, with an increased overall methylation level. After 5-aza treatment, the Sox2 promoter was in a non-methylated state, and its mRNA expression increased, which hindered the cell differentiation.

How far is brain-inspired artificial intelligence away from brain?

Fueled by the development of neuroscience and artificial intelligence (AI), recent advances in the brain-inspired AI have manifested a tipping-point in the collaboration of the two fields. AI began with the inspiration of neuroscience, but has evolved to achieve a remarkable performance with little dependence upon neuroscience. However, in a recent collaboration, research into neurobiological explainability of AI models found that these highly accurate models may resemble the neurobiological representation of the same computational processes in the brain, although these models have been developed in the absence of such neuroscientific references. In this perspective, we review the cooperation and separation between neuroscience and AI, and emphasize on the current advance, that is, a new cooperation, the neurobiological explainability of AI. Under the intertwined development of the two fields, we propose a practical framework to evaluate the brain-likeness of AI models, paving the way for their further improvements.

Evaluation of Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio on Predicting Responsiveness to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Objective: Neutrophil-lymphocyte ratio (NLR) and Platelet-lymphocyte ratio (PLR) have been proposed as prognostic biomarkers in multiple cancers. However, the implications of NLR and PLR in the responsiveness to neoadjuvant chemoradiotherapy (nCRT) remain to be clarified in locally advanced rectal cancer (LARC) patients. This retrospective study investigated the prognostic value of NLR and PLR in nCRT responsiveness of LARC patients. Methods: A total number of 86 patients diagnosed with LARC and treated with nCRT and total mesorectal excision were retrospectively followed from 2013 to 2016. Receiver operating characteristic (ROC) curve was used to determine the cutoff values of NLR and PLR, and the patients were divided into NLR elevation and NLR decrease groups, or PLR elevation and PLR decrease groups. The correlation between NLR and PLR changes, and clinicopathological factors were analyzed. The relationship between NLR and PLR changes and the curative responsiveness towards nCRT were further evaluated. Results: NLR and PLR changes after nCRT were significantly correlated with the distance of tumors to the anus and BMI (body mass index) (P < 0.05). The clinical remission rate of patients with NLR reduction was 72.09% (31/43), which was significantly higher than that in patients with NLR increment (22/43, 51.16%). There was no significant difference in the clinic remission rate between the patients with PLR reduction and those with PLR increment (P > 0.05). However, the pathological responsiveness rate was significantly higher in patients with PLR reduction (21/43, 48.84%) when compared to the ones with PLR increment (9/43, 20.9%) (P = 0.036). Conclusion: Our data indicate that in LARC patients with nCRT, the reduction of NLR and the reduction of PLR could serves as predictors for the clinic remission rate and pathological responsiveness rate, respectively. The combination of NLR and PLR changes may be employed as a simple and effective prognostic parameter to predict the treatment outcome of nCRT in LARC.

Effects of KCa channels on biological behavior of trophoblasts.

The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

Immune Deviation in the Decidua During Term and Preterm Labor.

The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.

G-CSF: A vehicle for communication between trophoblasts and macrophages which may cause problems in recurrent spontaneous abortion.

INTRODUCTION: The etiology of approximately half of patients with recurrent spontaneous abortion (RSA) has yet to be established. Granulocyte-colony stimulating factor (G-CSF) exerts a protective effect on pregnancy and its absence may lead to pregnancy failure. However, the effects and mechanisms of G-CSF activities have not been fully explored. Therefore, we aimed at evaluating whether a loss of G-CSF induces RSA by affecting cell communication at the maternal-foetal interface. METHODS: Villous and decidual tissues were obtained from participants and expression levels of G-CSF determined by qRT-PCR, Western blot and immunohistochemistry. G-CSF levels in trophoblasts were downregulated by siRNA. Exosomes were extracted from trophoblasts and co-cultured with macrophages. Molecular expression levels of key genes were determined by qRT-PCR and Western blot. Migration and proliferation of cells were evaluated by transwell and CCK8 assays. The RSA mice models were intraperitoneally administered with G-CSF to assess pregnancy outcomes and expression profiles of G-CSF as well as its receptor at the mother-foetal interface. RESULTS: Relative to the decidua, G-CSF was highly expressed in the villus, and expression levels were low in RSA tissues compared to normal tissues. Down-regulation of G-CSF in the trophoblast cell line (HTR-8/SVneo) by siRNA was associated with a decrease in cell activities. Trophoblast-derived exosomes inhibited the activation of the macrophage cell line (RAW264.7), whereas G-CSF free exosomes had no effects on macrophage activation. Intraperitoneal administration of G-CSF improved pregnancy outcomes in RSA mice and increased the amounts of G-CSF at the maternal-foetal interface. DISCUSSION: G-CSF levels were downregulated in villi of RSA patients. The absence of G-CSF impaired the proliferation as well as migration capacities of trophoblasts, and weakened the suppression of trophoblasts against macrophages. This implies that suppressed G-CSF levels may be a key factor in RSA occurrence. G-CSF decreased the rate of abortion in RSA mice, thus, it could be a treatment option for RSA patients.