Revealing synergetic structural activation of a CuAu surface during water-gas shift reaction.

Bimetallic alloy catalysts show strong structural and compositional dependence on their activity, selectivity, and stability. Often referred to as the "synergetic effect" of two metal elements in the alloys, their detailed dynamic information, structurally and chemically, of catalyst surface under reaction conditions remains largely elusive. Here, using aberration-corrected environmental transmission electron microscopy, we visualize the atomic-scale synergetic surface activation of CuAu under a water­gas shift reaction condition. The unique "periodic" structural activation largely determines the dominating reaction pathway, which is related to a possible "carboxyl" reaction route corroborated by density functional theory­based calculation and ab initio molecular dynamics simulation. These results demonstrate how the alloy surface is activated and catalyzes the chemical reaction, which provides insights into catalyst design with atom precision.

Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Ice recrystallization inhibition mechanism of zwitterionic poly(carboxybetaine methacrylate).

Understanding the ice recrystallization inhibition (IRI) mechanism is of fundamental importance for the rational design of novel antifreeze protein mimetics and reducing IR-related damage. In this communication, using quantitive experimental methods and molecular dynamics simulations we demonstrate that zwitterionic poly(carboxybetaine methacrylate) (PCBMA) can serve as a novel IRI-active substance. This work unravels the atomic-level details of the IRI mechanism of zwitterionic antifreeze protein mimetics and provides insight into the development of next-generation antifreeze protein mimetics.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson's Disease and Drug-Induced Parkinsonism.

BACKGROUND: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson's disease (PD). METHODS: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [18F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. RESULTS: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). CONCLUSION: Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

A Simultaneous Pipe-Attribute and PIG-Pose Estimation (SPPE) Using 3-D Point Cloud in Compressible Gas Pipelines.

An accurate estimation of pipe attributes, pose of pipeline inspection gauge (PIG), and downstream pipeline topology is essential for successful in-line inspection (ILI) of underground compressible gas pipelines. Taking a 3D point cloud of light detection and ranging (LiDAR) or time-of-flight (ToF) camera as the input, in this paper, we present the simultaneous pipe-attribute and PIG-pose estimation (SPPE) approach that estimates the optimal pipe-attribute and PIG-pose parameters to transform a 3D point cloud onto the inner pipe wall surface: major- and minor-axis lengths, roll, pitch, and yaw angles, and 2D deviation from the center of the pipe. Since the 3D point cloud has all spatial information of the inner pipe wall measurements, this estimation problem can be modeled by an optimal transformation matrix estimation problem from a PIG sensor frame to the global pipe frame. The basic idea of our SPPE approach is to decompose this transformation into two sub-transformations: The first transformation is formulated as a non-linear optimization problem whose solution is iteratively updated by the Levenberg-Marquardt algorithm (LMA). The second transformation utilizes the gravity vector to calculate the ovality angle between the geometric and navigation pipe frames. The extensive simulation results from our PIG simulator based on the robot operating system (ROS) platform demonstrate that the proposed SPPE can estimate the pipe attributes and PIG pose with excellent accuracy and is also applicable to real-time and post-processing non-destructive testing (NDT) applications thanks to its high computational efficiency.

C2RL: Convolutional-Contrastive Learning for Reinforcement Learning Based on Self-Pretraining for Strong Augmentation.

Reinforcement learning agents that have not been seen during training must be robust in test environments. However, the generalization problem is challenging to solve in reinforcement learning using high-dimensional images as the input. The addition of a self-supervised learning framework with data augmentation in the reinforcement learning architecture can promote generalization to a certain extent. However, excessively large changes in the input images may disturb reinforcement learning. Therefore, we propose a contrastive learning method that can help manage the trade-off relationship between the performance of reinforcement learning and auxiliary tasks against the data augmentation strength. In this framework, strong augmentation does not disturb reinforcement learning and instead maximizes the auxiliary effect for generalization. Results of experiments on the DeepMind Control suite demonstrate that the proposed method effectively uses strong data augmentation and achieves a higher generalization than the existing methods.

[Analysis of blood flow of penile cavernous artery in 2 568 cases of erectile dysfunction].

OBJECTIVE: To analyze the blood flow parameters of the cavernous arteries of ED patients after injection of vasoactive drugs, and to explore the differences in blood flow of the cavernous arteries in different erectile states. METHODS: Retrospectively analyzed the penile cavernous arterial blood flow parameters of 2568 adult male ED patients after injection of the vasoactive drug (alprostadil). The patients were divided into three groups: maintaining erection group with EHS (erection hardness score) ≥ 3 and sustained erection time ≥ 20 minutes (967 cases), nonpersistent erection group with EHS≥3 and sustained erection time<5 minutes (788 cases), and incomplete erection group with EHS<3 (813 cases). Compared the parameters of age, EHS, duration of erection, cavernous artery peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) among the three groups respectively. The maintaining erection group was divided into the youth group (757 cases) which aged less than 40 years old and the middle-aged and elderly group (210 cases) with 40 years old or over. The parameters of PSV, EDV and RI between the two groups were compared. The incomplete erection group were divided into the good blood supply group (407 cases) with the bilateral PSV ≥35cm/s and the insufficient blood supply group (252 cases) with the bilateral PSV<35cm/s. The parameters of age, EHS, EDV and RI between the two groups were compared. RESULTS: The age, PSV, EDV and RI of the three groups were significantly different (P<0.01). In the maintaining erection group, the PSV of the young group was significantly higher than that of the middle-aged and elderly group (P<0.05), but there was no statistically significant difference in EDV and RI (P>0.05). In the incomplete erection group, the EHS, PSV, EDV, and RI of the good blood supply group were significantly higher than those of the insufficient blood supply group (P<0.05), while the age was significantly lower than that of the latter (P<0.01). CONCLUSION: The injection of vasoactive drugs combined with color Doppler ultrasound can directly reflect the blood supply of the cavernous arteries of the penis. The better the erection state, the better the blood supply of cavernous arteries. The middle-aged and elderly people are more likely to have cavernous arteries problem of insufficient blood supply than the young people.

Desilylative Coupling Involving C(sp2)-Si Bond Cleavage on Metal Surfaces.

Desilylative coupling involving C-Si bond cleavage has emerged as one of the most important synthetic strategies for carbon-carbon/heteroatom bond formation in solution chemistry. However, in on-surface chemistry, C-Si bond cleavage remains a synthetic challenge. Here, we report the implementation of C(sp2)-Si bond cleavage and subsequent C-C bond formation on metal surfaces. The combination of scanning tunneling microscopy and density functional theory calculation successfully reveals that the incorporation of the C-Br group on the arylsilanes is critical to the success of this desilylative coupling reaction on metal surfaces. Our study represents a promising approach for the removal of protecting silyl groups in on-surface chemistry.

Ultrafine Ruthenium Clusters Shell-Embedded Hollow Carbon Spheres as Nanoreactors for Channel Microenvironment-Modulated Furfural Tandem Hydrogenation.

Rationally modulating the catalytic microenvironment is important for targeted induction of specific molecular behaviors to fulfill complicated catalytic purposes. Herein, a metal pre-chelating assisted assembly strategy is developed to facilely synthesize the hollow carbon spheres with ultrafine ruthenium clusters embedded in pore channels of the carbon shell (Ru@Shell-HCSs), which can be employed as nanoreactors with preferred electronic and geometric catalytic microenvironments for the efficient tandem hydrogenation of biomass-derived furfural toward 2-methylfuran. The channel-embedding structure is proved to confer the ultrafine ruthenium clusters with an electron-deficient property via a reinforced interfacial charge transfer mechanism, which prompts the hydrogenolysis of intermediate furfuryl alcohol during the tandem reaction, thus resulting in an enhanced 2-methylfuran generation. Meanwhile, lengthening the shell pore channel can offer reactant molecules with a prolonged diffusion path, and correspondingly a longer retention time in the channel, thereafter delivering an accelerated tandem hydrogenation progression. This paper aims to present a classic case that emphasizes the critical role of precisely controlling the catalytic microenvironment of the metal-loaded hollow nanoreactors in coping with the arduous challenges from multifunctional catalyst-driven complex tandem reactions.

Bioactivity of orange-spotted grouper (Epinephelus coioides) cathepsin L: Proteolysis of bacteria and regulation of the innate immune response.

Cathepsin L (CTSL) is a cysteine endopeptidase involved in protein degradation mainly in lysosomes. Following activation in an acidic environment, it plays a key role in a variety of physiological, immunological, and pathological processes. The biological function of CTSL in teleost remains unclear. Immunohistochemical analysis revealed that CTSL was expressed mainly in lymphoid organs, head kidney, trunk kidney, and liver, which particularly was expressed in leukocyte-like cells. We performed two forms of recombinant CTSL (rCTSL and rTCTSL) derived from orange-spotted grouper (Epinephelus coioides) to elucidate the role of CTSL in teleost innate immunity, based on differences in immune-related gene expression. We determined that rCTSL has a proteolytic function whereas rTCTSL does not. Under CTSL activation, we observed increases in IL-1ß, IL-6, IL-12, IFNγ, CCL-1, CCL-3, epinecidin-1, lysozyme, and IgM. The bacteriolytic activity of rCTSL was more pronounced against Gram-positive bacteria than Gram-negative bacteria. Our findings indicate CTSL plays multiple roles in the reactions of innate immunity.

Prediction of Adverse Pregnancy Outcomes Using Crown-Rump Length at 11 to 13 + 6 Weeks of Gestation.

OBJECTIVES: To assess the risk of a fetus with a smaller or larger than expected crown-rump length (CRL) for adverse pregnancy outcomes. METHODS: The data of 960 healthy singleton pregnancies conceived via in vitro fertilization were retrospectively collected. Fetal CRL was measured between 11 and 13 + 6 weeks of gestation, and small and large fetal CRLs were defined as fetuses below the 10th and above the 90th centiles, respectively. Multiple logistic regression analysis was performed to assess the risk for adverse pregnancy outcomes. RESULTS: The mean birth weights of fetuses with small, normal, and large CRLs were 3002 g, 3205 g, and 3378 g, respectively. A small fetal CRL was associated with an increased risk of smaller-than-gestational-age neonates (adjusted odds ratio [aOR], 2.79; 95% confidence interval [CI], 1.53-5.08; P < .001) and preterm delivery before 34 gestational weeks (aOR, 6.48; 95% CI, 1.36-30.79; P = .019). A large fetal CRL was associated with an increased risk of large-for-gestational-age (LGA) neonates, and the risk persisted even after adjustment for well-known risk factors of macrosomia, such as pre-pregnancy body mass index, gestational diabetes, and excessive gestational weight gain (aOR, 3.67; 95% CI, 2.04-6.59; P < .001). However, a large fetal CRL was associated with a decreased risk of gestational diabetes (aOR, 0.10; 95% CI, 0.01-0.76; P = .026). CONCLUSIONS: Fetal CRL measured at 11 to 13 + 6 weeks gestation is worth using as a predictor of LGA as well as small for gestational age or preterm delivery.

First report of fusarium wilt disease caused by Fusarium equiseti on grafted watermelon in Korea.

In Korea, most of the grafted watermelons are a fusion of bottle gourd (Lagenaria siceraria) as a rootstock and watermelon (Citrullus lanatus) as a scionstock (Lee et al., 2010). Currently, we have collected several samples from grafted watermelon displaying symptoms of yellowing, withered and wilting leaves. When the symptomatic stem was excised, browning vascular tissues were observed due to the colonization of fungal pathogen. From the samples obtained, 25 fungal isolates were identified as species of Fusarium. Among 25 isolates, 18 were identified as Fusarium oxysporum, four as Fusarium solani, and three as Fusarium equiseti (F. equiseti) . Initial assessment showed that one of the F. equiseti isolates (NIHHS 16-126) was highly virulent to rootstock. Interestingly, this is the first time F. equiseti has been identified pathogenic to grafted watermelon. NIHHS 16-126 isolate was collected from watermelon cultivation field around Buyeo-gun (36.25951°N, 126.92044°E) county. Disease incident was estimated to infect approximately 10% of the watermelon plants cultivated in this area. NIHHS 16-126 isolate was examined to confirm its identity. On potato dextrose agar, colonies appeared yellowish-brown while the aerial mycelium was whitish to peach in color. Macroconidia were relatively long (20.21 - 51.13 × 2.30 - 4.5 µm, n=50), comprise of 3-6 septa, curvature shape and its conidiophores were with monophialides. However, microconidia formation was not observed. These morphological characteristics resemble F. equiseti characters as described by Hyun (2019). For molecular identification, an internal transcribed spacer of ribosomal DNA (ITS-rDNA), elongation factor-1α (EF-1α), and beta-tubulin (ß-tub) genes were sequenced using primer pairs of ITS1/ITS4 (White et al., 1990), EF1-728F/EF1-986R (Glass and Donaldson 1995), and Bt2a/Bt2b (Carbone and Kohn 1999). BLASTN analysis revealed that ITS-rDNA (LC648248), EF-1α (LC648250), and ß-tub (LC648249) sequences were 99-100% identical to F. equiseti reference sequences (KF515650, KF747331, and KF747330) infected Avicennia marina in China (Lu 2014). Phylogenetic analysis of concatenated ITS-rDNA, EF-1α and ß-tub sequences showed that this isolate clustered in the same clade as F. equiseti, confirming its identity as F. equiseti. For the inoculation, roots of 12-days-old seedlings (watermelon and bottle gourd, n=10 each) were dipped in the conidia suspension (1x106 conidia/µL) for 30 min. Inoculated seedlings were planted in the soil before being transferred to the greenhouse (temperature; 30°C, daylight; 14 hours). Control plants were inoculated with sterile water. Results showed that after 21 days post-inoculation, all inoculated bottle gourd seedlings (n=10) wilted and eventually died. In contrast, none of the inoculated watermelons or control seedlings were affected. Re-isolation of three fungal isolates (infected root) showed that their morphology and gene markers sequence were identical to the original isolates thus fulfilled Koch's postulates. Bottle gourd is the most preferred rootstock for grafted watermelons among Korean farmers due to its ability to resist Fusarium spp. infection. Therefore, the identification of F. equiseti as a fungal that is pathogenic to rootstock is crucial information to manage fusarium wilt disease among grafted watermelon. To our knowledge, this is the first report confirming F. equiseti infection in grafted watermelon plants in Korea.

An Area Partitioning and Subgraph Growing (APSG) Approach to the Conflation of Road Networks.

A road network represents a set of road objects in a geographic area and their interconnections, and it is an essential component of intelligent transportation systems (ITS) enabling emerging new applications such as dynamic route guidance, driving assistance systems, and autonomous driving. As the digitization of geospatial information becomes prevalent, a number of road networks with a wide variety of characteristics may coexist. In this paper, we present an area partitioning and subgraph growing (APSG) approach to the conflation of two road networks with a large difference in the level of details and representation rules. Our area partitioning (AP) scheme partitions the geographic area using the Network Voronoi Area Diagram (NVAD) of the low-detailed road network. Next, a subgraph of the high-detailed road network corresponding to a complex intersection is extracted and aggregated into a supernode so that high precision can be achieved via 1:1 road object matching. For the unmatched road objects due to missing road objects and different representation rules, we also propose a subgraph growing (SG) scheme that sequentially inserts a new road object while keeping the consistency of its connectivity to the matched road objects by the AP scheme. From the numerical results at Yeouido, Seoul, Korea, we show that our APSG scheme can achieve an outstanding matching performance in terms of the precision, recall, and F1-score.

BACTERIAL IDENTIFICATION AND ANTIBIOTIC SENSITIVITY FROM THE ABSCESSES OF CAPTIVE TORTOISES-CLINICAL ANTIBIOTIC RECOMMENDATIONS.

Bacterial abscesses are commonly seen in tortoises. The morbidity and the resultant mortality are high. Multifactorial problems, antibiotics misapplication. and antibiotic-resistant bacteria make abscess treatment complicated and ineffective. This study identifies the etiological bacterial species and determines the best antibiotics for abscess treatment in captive tortoises. Sterile swab specimens from 40 tortoises with abscesses were analyzed using the Analytical Profile Index (API) system. Sixty-five bacteria species were identified covering facultative anaerobic gram-negative (n = 30, 46.2%), facultative anaerobic gram-positive (n = 19, 29.2%), and aerobic gram-negative bacteria (n = 16, 24.6%). The antibiotic sensitivity of these bacteria to 30 antibiotics was assessed using the Kirby-Bauer disk-diffusion method. Greater than 80% anaerobic gram-negative bacterial species showed sensitivity to amikacin and ceftazidime. Greater than 80% anaerobic gram-positive bacterial species were sensitive to amoxicillin, ampicillin, carbenicillin, and penicillin. In addition, more than 80% aerobic gram-negative bacterial species were sensitive to ceftazidime, colistin sulphate, amikacin, gentamicin, kanamycin, polymyxin B, and tobramycin. This study provides clinicians significant information for initial antibiotic options, which could elevate the abscess therapy success rate and improve the life quality of tortoises.

[Artificial intelligence-based fluorescence method versus traditional flow cytometry in detection of sperm DNA fragmentation index].

OBJECTIVE: To compare the result of the artificial intelligence (AI) recognition-based fluorescence method and that of traditional flow cytometry in the examination of the sperm DNA fragmentation index (DFI) and assess the reliability of the AI-based fluorescence detection. METHODS: Using flow cytometry and the AI-based fluorescence method, we examined the sperm DFI in the semen samples collected from 338 outpatients. We analyzed the correlation between the results and compared the positive rates detected by the two methods. We repeated the AI-based fluorescence method twice for each semen sample to observe its technical stability in the detection of sperm DFI. RESULTS: The result of flow cytometry was well correlated with that of the AI-based fluorescence method in the detection of sperm DFI (R2 = 0.7131), but poorly correlated for low-concentration, sticky semen and some other extreme samples (R2 = 0.2065). No statistically significant difference was found between the two methods in the positive rate of detection. The AI-based fluorescence method exhibited an excellent technical stability (R2 = 0.9671). CONCLUSION: The AI-based fluorescence method has an excellent technical stability in the detection of sperm DFI and the result is not significantly different from that of traditional flow cytometry.

Catalytically Stable Potassium Single-Atom Solid Superbases.

Solid superbases can catalyze diverse reactions under mild conditions, while they suffer from aggregation of basic sites and poor stability during recycling. Here we report a new generation of solid superbases derived from K single atoms (SAs) prepared by a tandem redox strategy. The initial redox reaction takes place between base precursor KNO3 and graphene support, producing K2 O at 400 °C. Further increasing the temperature to 800 °C, the graphene reduces K2 O to K anchored by its vacancies, leading to the generation of K SAs (denoted as K1 /G). The source of basicity in the K1 /G is K SAs, and neighboring single atoms (NSAs) possess superbasicity, which is different from conventional basicity originated from oxygen and nitrogen atoms. Due to the superbasicity as well as high dispersion and anchoring of basic sites, the K1 /G shows excellent catalytic activity and stability in transesterification reaction, which is much superior to the reported catalysts.

Bone marrow cells are differentiated into MDSCs by BCC-Ex through down-regulating the expression of CXCR4 and activating STAT3 signalling pathway.

Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway.

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.