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Abstract The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.

Abstract Background Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. Methods We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. Results The TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR − 6.6%. Brain metastasis-free survival was better in the group with a TSR

Abstract Background Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. Methods/design This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. Discussion This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. Ethics and dissemination Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. Trial registration ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Cold storage is one of the most effective methods to maintain postharvest fruit quality. However, loquat fruits are prone to chilling injury (CI) during cold storage, appearing as symptoms such as browning and pitting, which leads to quality deterioration and economic losses. In this study, the effects of melatonin on CI alleviation and the potential role of reactive oxygen species (ROS) metabolism in loquat fruit were investigated. The results showed that 50 μM melatonin was the optimal concentration to inhibit the increase in CI index and cell membrane permeability. Moreover, compared to control fruits, 50 μM melatonin inhibited the malonaldehyde (MDA) content, O2−. production rate and H2O2 content (ROS accumulation) by 17.8%, 7.2% and 11.8%, respectively, during cold storage. Compared to non-treated loquats, 50 μM melatonin maintained higher levels of 1-diphenyl-2-picrylhydrazyl radical-scavenging ability and reducing power, as well as the contents of ascorbic acid (AsA) and glutathione (GSH). Additionally, 50 μM melatonin enhanced the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) by increasing relevant gene expressions. The activities of SOD, CAT and APX were increased by up to 1.1-, 1.1- and 1.1-times (16 d) by melatonin, as compared with the control fruits. These findings indicate that melatonin mitigation of CI is involved in maintaining cellular redox apphomeostasis in loquat fruit during cold storage.

ObjectiveTo explore the effect of varying numbers of embryo washings prior to blastocyst formation in non-invasive preimplantation chromosome screening (NICS) on the accuracy of NICS results.MethodsIn this study, 68 blastocysts from preimplantation genetic testing (PGT)-assisted pregnancy were collected at our institution. On the fourth day of embryo culture, the embryos were transferred to a new medium for blastocyst culture and were washed either three times (NICS1 group) or ten times (NICS2 group). A trophectoderm (TE) biopsy was performed on the blastocysts, and the corresponding embryo culture media were collected for whole genome amplification (WGA) and high-throughput sequencing.ResultsThe success rate of WGA was 100% (TE biopsy), 76.7% (NICS1 group), and 89.5% (NICS2 group). The success rate of WGA in embryo medium on days 5 and 6 of culture was 75.0% (33/44) and 100% (24/24), respectively. Using TE as the gold standard, the karyotype concordance rate between the results of the NICS1 and NICS2 groups’ embryo culture medium samples and TE results was 43.5% (10/23) and 73.5% (25/34), respectively. The sensitivity and specificity of detecting chromosomal abnormalities were higher in the NICS2 group than in the NICS1 group when TE was used (83.3% vs 60.0%; 62.5% vs 30.8%, respectively). The false-positive rate and false-negative rate (i.e., misdiagnosis rate and missed diagnosis rate, respectively) were lower in the NICS2 group than in the NICS1 group (37.5% vs 69.2%; 16.7% vs 40.0%, respectively).ConclusionThe NICS yielded favorable results after ten washings of the embryos. These findings provide a novel method for lowering the amount of cell-free DNA contamination from non-embryonic sources in the medium used for embryo development, optimizing the sampling procedure and improving the accuracy of the NICS test.

Abstract Background Improving the accuracy of estimated fetal weight (EFW) calculation can contribute to decision-making for obstetricians and decrease perinatal complications. This study aimed to develop a deep neural network (DNN) model for EFW based on obstetric electronic health records. Methods This study retrospectively analyzed the electronic health records of pregnant women with live births delivery at the obstetrics department of International Peace Maternity & Child Health Hospital between January 2016 and December 2018. The DNN model was evaluated using Hadlock’s formula and multiple linear regression. Results A total of 34824 live births (23922 primiparas) from 49896 pregnant women were analyzed. The root-mean-square error of DNN model was 189.64 g (95% CI 187.95 g—191.16 g), and the mean absolute percentage error was 5.79% (95%CI: 5.70%—5.81%), significantly lower compared to Hadlock’s formula (240.36 g and 6.46%, respectively). By combining with previously unreported factors, such as birth weight of prior pregnancies, a concise and effective DNN model was built based on only 10 parameters. Accuracy rate of a new model increased from 76.08% to 83.87%, with root-mean-square error of only 243.80 g. Conclusions Proposed DNN model for EFW calculation is more accurate than previous approaches in this area and be adopted for better decision making related to fetal monitoring.

Banana is a typical cold-sensitive fruit; it is prone to chilling injury (CI), resulting in a quality deterioration and commodity reduction. However, the molecular mechanism underlying CI development is unclear. In this study, cold storage (7 °C for 5 days) was used to induce CI symptoms in bananas. As compared with the control storage (22 °C for 5 days), cold storage increased the CI index and cell membrane permeability. Moreover, we found that the expression levels of the WRKY transcription factor MaWRKY70 were increased consistently with the progression of CI development. A subcellular localization assay revealed that MaWRKY70 was localized in the nucleus. Transcriptional activation analyses showed that MaWRKY70 processed a transactivation ability. Further, an electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter (DLR) assays showed that MaWRKY70 was directly bound to the W-box motifs in the promoters of four lipoxygenase (LOX) genes associated with membrane lipid degradation and activated their transcription. Collectively, these findings demonstrate that MaWRKY70 activates the transcription of MaLOXs, thereby acting as a possible positive modulator of postharvest CI development in banana fruit.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case–control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33–0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia.

Abstract Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

In recent years, road waste treatment has become a hot topic, and how to solve and utilize these solid wastes is becoming an interesting research field. In order to explore the mechanical modification effect of waterborne polyurethane (PU) on short age road solid waste recycled aggregate, unconfined compression test and scanning electron microscope test were carried out on samples with different dry density and PU content. The dry density was 1.6 g cm ^−3 , 1.7 g cm ^−3 and 1.8 g cm ^−3 , and the PU content was 0%, 3%, 4%, 5% and 6%, respectively. The tested results show that, the strength of recycled aggregate (RA) increases with the increase of dry density. PU improves the strength and ductility of recycled aggregate (RA), and the residual strength and peak strength of RA increase with the increase of PU content. The peak strength and residual strength of waterborne polyurethane improved recycled aggregate (WPRA) increase with the increase of dry density, too. Polyurethane forms a three-dimensional network structure by film shape and linear shape, and its network structure can provide cohesion and effectively inhibit the crack propagation of the sample. The results demonstrate that adding appropriate amount of PU can effectively improve the mechanical properties of RA, which provides a technical reference for the recycling of RA.

Abstract Objective To investigate the effects of vaginal microecology and immune status on the pregnancy outcome of cervical cerclage. Methods The clinical data of 125 patients with cervical incompetence who underwent transvaginal cervical cerclage in our hospital from January 2018 to January 2021 were collected, based on which the associations of vaginal microecology and related immune cytokines (IL-1β, IL-6, IL-8 and TNF-α) with the cervical cerclage outcome were explored. Results All of the 125 patients had singleton pregnancies, who were aged 20–43 years, with a mean of (32.34 ± 5.17) years. The surgery was successful in 104 patients (full-term delivery or survival of premature infants), while unsuccessful in 21 patients (late miscarriage or death of premature infants), revealing a success rate of 83.20%. There were 70 full-term deliveries, 34 premature deliveries (28 survived while 6 died), and 15 late miscarriages. Univariate analysis revealed statistically significant differences in the timing of surgery, gestational age of cerclage, preoperative cervical canal length, genital tract infections and preoperative invasive procedures between the successful and unsuccessful groups (P 0.05). According to the multivariate analysis results, cerclage timing and genital tract infections were independent risk factors for postoperative pregnancy failure (P

Aiming at the problems of lack of potential implicit relation mining between entities and insufficient head entity information extraction in existing methods, a head entity-enhanced multi-hop attention implicit relations joint mining model Multi-Air (multi-hop attention implicit relations joint mining method) was proposed. The method first uses the BERT (bidirectional encoder representations from transformers) model to encode the features of the input sentence and predicts the position of the head entity through the Sigmoid function, and then uses the bidirectional gated recurrent unit (Bi-GRU) to enhance the feature of the head entity. After making full use of the high-level information of the head entities, the model can output the possible starting and ending positions of the tail entities with multiple relationships. Then the model continues to use the tail entities as the head entities of the next hop and iteratively perform the prediction of the multi-hop tail entities. At the same time, the model uses the attention weight to dynamically adjust the features of the learned entities and relationships so as to realize the mining of potential relationship triples in the plain text. The Multi-Air model has made good improvements in both the public dataset NYT and the civil aviation emergency dataset.

Obesity is a metabolic disease characterized by excessive fat storage, and the adipogenic differentiation of adipose-derived stromal cells (ADSCs) is closely linked to its occurrence. Growth differentiation factor 11 (GDF11), a well-known molecule in the field of anti-aging, also has great potential in regulating stem cell differentiation. In this study, we found that GDF11 inhibited adipogenic differentiation of human ADSCs in vitro by activating the WNT/β-catenin and SMAD2/3 pathways while inhibiting the AKT pathway. Moreover, the transcription factor Kruppel-like factor 15 (KLF15) was discovered to be an important downstream factor for GDF11 in inhibiting adipogenesis via the WNT/β-catenin pathway. Furthermore, AlphaFold2 structure prediction and inhibitor-blocking experiments revealed that ALK5 is a functional receptor of GDF11. Collectively, we demonstrated that GDF11 is a potential target for inhibiting adipogenic differentiation and combating obesity.

Non-Hermitian skin effect (NHSE), where huge modes are accumulated at system boundaries, offers new possibility for steering the transport and localization of light by non-Hermiticity. Here, the direction-dependent NHSE is proposed in a photonic waveguide array via spatially complex modulation, where the skin modes tend to localize at different boundaries for opposite propagation directions. We utilize complex modulation to arouse anisotropic coupling between symmetric and anti-symmetric modes in multimode waveguides and further match the refractive index of adjacent waveguides. In this way, a non-Hermitian Su–Schrieffer–Heeger (SSH) lattice that supports NHSE is achieved. In particular, the anisotropic coupling is highly unidirectional. For forward direction, it allows mode conversion from antisymmetric modes to symmetric modes. However, the process is forbidden for backward direction. As a result, the skin modes tend to locate at lower boundary for forward propagation but the localization direction is reversed for backward injection. Our results provide a potential platform to investigate NHSE on photonic chips and may find applications in non-magnetic unidirectional devices.

IntroductionThe prevalence of Gestational Diabetes Mellitus (GDM) is increasing globally, and high levels of triglyceride (TG) and low levels of free thyroxine (FT4) in early pregnancy are associated with an increased risk of GDM; however, the interaction and mediation effects remain unknown. The aim of the present study is to examine the impact of FT4 and TG combined effects on the prevalence of GDM and the corresponding casual paths among women in early pregnancy.Materials and methodsThis study comprised 40,156 pregnant women for whom early pregnancy thyroid hormones, fasting blood glucose as well as triglyceride were available. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines, and the pregnant women were grouped and compared according to the results.ResultsAn L-shaped association between FT4 and GDM was observed. The prevalence of GDM increased with increasing TG levels. After accounting for multiple covariables, the highest risk for GDM was found among pregnant women of lower FT4 with the highest TG concentrations (odds ratio, 2.44, 95% CI, 2.14 to 2.80; P

Osteosarcoma is a malignant bone tumor, which often occurs in adolescents. However, surgical resection usually fails to completely remove the tumor clinically, which has been the main cause of postoperative recurrence and metastasis, resulting in the high death rate of patients. At the same time, osteosarcoma invades a large area of the bone defect, which cannot be self-repaired and seriously affects the life quality of the patients. Herein, a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods (GNRs) and nanohydroxyapatite (nHA), which possessed excellent photothermal effect, was constructed to eradicate residual tumor after surgery and bone regeneration. In vitro, K7M2wt cells (a mouse bone tumor cell line) can be efficiently eradicated by photothermal therapy of the hybrid hydrogel. Meanwhile, the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells. The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma. Therefore, the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration, which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.

Abstract Background The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. Methods/design A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. Discussion To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. Trial registration number ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

Early life is a vital period for mammals to be colonized with the microbiome, which profoundly influences the development of the intestinal immune function. For neonates to resist pathogen infection and avoid gastrointestinal illness, the intestinal innate immune system is critical. Thus, this review summarizes the development of the intestinal microbiome and the intestinal innate immune barrier, including the intestinal epithelium and immune cells from the fetal to the weaning period. Moreover, the impact of the intestinal microbiome on innate immune development and the two main way of early-life intervention including probiotics and fecal microbiota transplantation (FMT) also are discussed in this review. We hope to highlight the crosstalk between early microbial colonization and intestinal innate immunity development and offer some information for early intervention.

Abstract Background Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. Methods A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. Results Caregivers tended to underestimate children’s weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children’s physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children’s nutrition intake and physical activity, and preferred online approaches. Conclusions Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Abstract Background Transcription factors (TFs) may be engaged in reciprocal regulatory circuits with certain miRNAs to maintain cellular homeostasis. Disequilibrium of the reciprocities by certain tumor-related stimuli may give rise to deregulation of downstream cellular signaling pathways, thus promoting malignant tumor phenotypes. Specificity Protein 1 (SP1) is the most representative member of the tumor-related transcription factors. Previous studies disclosed that SP1 can transcriptionally regulate miRNAs and coding genes to facilitate tumor progression. In our study, we used bioinformatic analysis to predict several SP1-binding sites within the miR-320a promoter and found that SP1 is a predicted target gene of miR-320a. Therefore, we hypothesize a reciprocal regulatory link between SP1 and miR-320a that participates in colorectal cancer (CRC) development Methods We performed bioinformatic analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, dual-luciferase reporter assays, and a series of in vitro and in vivo functional assays to describe a novel SP1/miR-320a reciprocal interaction in CRC Results First, we found that miR-320a was significantly downregulated in CRC tissues and cell lines. Consistent with findings in other cancers, miR-320a exhibited inhibitory effects on cell growth and invasion of CRC in vitro and in vivo. Moreover, we identified SP1 as a target gene of miR-320a, and ectopic SP1 expression partly abolished miR-320a-induced inhibitory effects. Conversely, we confirmed that SP1 interacts with the miR-320a promoter, leading to depression of miR-320a. This illustrates a double-negative feedback loop between miR-320a and SP1. Additionally, based on the fact that SP1 promotes MACC1 transcription, we determined via immunoblotting that the oncogenic MACC1/MET signaling pathway was inactivated in the context of miR-320a-induced SP1 downregulation Conclusion Taken together, our study is the first to describe a miR-320a/SP1 negative reciprocal interaction, which contributes to cell growth and invasion in CRC through modulation of the MACC1/MET signaling pathway.

Abstract Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects. In traditional tumour therapy, the systemic toxicity of chemotherapeutic drugs, invasive surgical resection, intractable tumour recurrence, and metastasis are major threats to the patients’ lives in the clinic. Fortunately, biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis, suggesting new promising antitumour therapies. In addition, maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients, and investment in treatment can result in a multitude of burdens to society. Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration. More interestingly, an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option. Herein, we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair. Furthermore, we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.

Abstract China has the largest and fastest‐growing breast milk substitutes (BMSs) market and a disproportionately low exclusive breastfeeding rate. Many BMS manufacturers have established Chinese e‐commerce stores. This marketing is of concern as it is likely to undermine breastfeeding. This study aimed to identify: (1) the marketing themes and strategies used to promote BMSs on the Chinese BMSs e‐commerce websites; (2) if and how digital BMSs marketing may deviate from the World Health Organization Code of Marketing of Breast Milk Substitutes (the Code) recommendations. Content analysis was conducted on the flagship websites of 10 BMSs companies on the Chinese e‐commerce platform “TMall” in July 2019. The main landing page (n = 10) of the flagship TMall website and the product description page (n = 113) of all individual formulas (Stages 1–3) within each company's TMall website were examined. The content was analysed and coded using an iterative thematic analysis approach. Emphasis on Premiumization and Science & Nutrition was the most commonly used marketing approaches. A total of 27.4% of the product description pages sampled used images of infants (

Abstract Background High-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate the immune response of the T cell. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Methods Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Based on our previous discoveries, we propose to investigate the distribution of neoantigens with different immunogenicity abilities in 3D genome and propose to adopt this important information into neoantigen prediction. Results We retrospect the DNA origins of the immuno-positive and immuno-negative neoantigens in the context of 3D genome and discovered that DNA loci of the immuno-positive neoantigens and immuno-negative neoantigens have very different distribution pattern. Specifically, comparing to the background 3D genome, DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We thus used this information into neoantigen prediction and demonstrated the effectiveness of this approach. Conclusion We believe that the 3D genome information will help to increase the precision of neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

(1) Background: Trace elements play important roles in gestational diabetes mellitus (GDM), but the results from reported studies are inconsistent. This study aimed to examine the association between maternal exposure to V, Cr, Mn, Co, Ni, and Se in early pregnancy and GDM. (2) Methods: A nested case-control study with 403 GDM patients and 763 controls was conducted. Trace elements were measured using inductively coupled plasma-mass spectrometry in plasma collected from pregnant women in the first trimester of gestation. We used several statistical methods to explore the association between element exposure and GDM risk. (3) Results: Plasma V and Ni were associated with increased and decreased risk of GDM, respectively, in the single-element model. V and Mn were found to be positively, and Ni was found to be negatively associated with GDM risk in the multi-element model. Mn may be the main contributor to GDM risk and Ni the main protective factor against GDM risk in the quantile g computation (QGC). 6.89 μg/L~30.88 μg/L plasma Ni was identified as a safe window for decreased risk of GDM. (4) Conclusions: V was positively associated with GDM risk, while Ni was negatively associated. Ni has dual effects on GDM risk.

Background: Bronchial Dieulafoy's disease (BDD), characterized by constant diameter arterial malformation, is rare, especially among infants. The pathogenesis and clinical features of pediatric patients are unknown. Misdiagnosis and biopsy operations may lead to potential massive hemorrhage, which endangers the patient's life.Case Presentation: Here, we present a case of a 9-month-old boy who was diagnosed with BDD with massive hemoptysis. The boy was cured by embolization of the bronchial artery and was in good health at the 1-year follow-up. In addition, we searched PubMed, Google Scholar, and Web of Science databases using keyword “Bronchial Dieulafoy's Disease (BDD)” and found six additional cases of pediatric BDD.Conclusion: It is still insufficient to draw a conclusion about the origin of the disease. Bronchial angiography and endobronchial ultrasonography are considered promising methods to diagnose Dieulafoy's disease of the bronchus. Bronchoscopy with transbronchial biopsy should not be deployed due to the high risk of fatal hemorrhage. Explicit clinical case reports of BDD are needed to enhance the understanding of this rare disease.

Artemisia argyi H. Lév. and Vaniot is a traditional medical herb that has been used for a long time in China and other Asian counties. Essential oil is the main active fraction of Artemisia argyi H. Lév. and Vaniot, and its anti-inflammatory potential has been observed in vitro and in vivo. Here, we found that the essential oil of Artemisia argyi H. Lév. and Vaniot (EOAA) inhibited monosodium urate (MSU)- and nigericin-induced NLRP3 inflammasome activation. EOAA suppressed caspase-1 and IL-1β processing and pyroptosis. NF-κB p65 phosphorylation and translocation were also inhibited. In addition, EOAA suppressed nigericin-induced NLRP3 inflammasome activation without blocking ASC oligomerization, suggesting that it may inhibit NLRP3 inflammasome activation by preventing caspase-1 processing. Our study thus indicates that EOAA inhibits NLRP3 inflammasome activation and has therapeutic potential against NLRP3-driven diseases.

The status of breastfeeding practices remains unsatisfactory across China, but regional differences persist. However, disaggregated data for specific provinces are limited. This representative survey determined the status of breastfeeding and factors associated with breastfeeding practices in Shanghai. The questionnaire was designed in compliance with indicators for assessing infant and young child-feeding practices defined by the World Health Organization and the United Nations Children’s Fund (UNICEF). A total of 2665 children aged two years and younger (0–730 days) were investigated, among whom 1677 were aged under six months. The early initiation of breastfeeding (EIBF) rate was 60.3%. Among children aged under six months, 43.4% were exclusively breastfed (EBF). The univariate regression analysis showed that the EBF rate was influenced by multiple factors, including individual, socioeconomic, workplace and employment, and health system. The subsequent multivariate analysis suggested that mothers with a higher rate of EBF shared the following characteristics: intention to breastfeed during pregnancy, breastfeeding knowledge, and higher satisfaction with support through the healthcare system after delivery. The rate of EBF in Shanghai is over 40%, and supporting breastfeeding requires measures at multiple levels, including individual attributes, women’s work and employment conditions, breastfeeding knowledge, and health services.

We theoretically investigate the time-domain dynamics in a non-Hermitian electric circuit network with anti-parity-time (anti-PT) symmetry, which is consisted of amplified resonant LRC circuits connected by resistors. The effective coupling strength and on-site potential can be flexibly tuned via controlling the resistance value and resonant frequencies of LRC circuits, respectively. Therein, we are able to realize all three symmetry phases of the system, including anti-PT symmetric, intermediate, and broken phases, which are distinguished from their band structures. We show the time evolution of the envelope of voltage is analogous to discrete diffraction as a single injection stimulates more and more channels over time. Specifically, the system exhibits constant intensity diffraction at the boundary between intermediate and broken phases as the voltages at different channels are of the same value during the evolution. The reason lies in the dispersionless band structure near exceptional points (EPs) and the related linear energy amplification. The results enrich the study of discrete diffraction and are helpful to further exploration of topological phenomena in anti-PT-symmetric systems.

BackgroundAssisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring’ later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET).ResultsGlobal methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5′UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B).ConclusionsART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.

PurposeWhile it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (

Early weaning leads to the disorder of the gut microbiome and gut mucosal barrier injury. Early intervention of gut microbiome colonization contributes to the development of the gut microbiome and gut function. The aim of this study was to explore the effects of Saccharomyces boulardii (S. boulardii) early intervention on the gut microbiome structure and gut mucosal barrier function of early-weaned rats. The results showed that S. boulardii early intervention improved growth performance along with a decrease in pathogenic bacteria, an increase in beneficial bacteria, a stable and complex microbiome, and a high level of microbial metabolism. Moreover, S. boulardii upregulated the mucosal barrier function including goblet cells and relative gene expression, tight junction, and sIgA level. Furthermore, S. boulardii suppressed the inflammatory response and promoted the anti-inflammatory response. Our study may provide a possible early intervention strategy for preventing an early weaning-induced disorder of the gut microbiome and loss of gut mucosal barrier function.

The recycling and reuse of construction waste have not only effectively protected natural resources but also promoted the sustainable development of the environment. Therefore, in this article, waterborne polyurethane (WPU) as a promising new polymer reinforcement material was proposed to reinforce the road demolition waste (RDW), and the mechanical performance of WPU-reinforced RDW (named PURD) was investigated using triaxial unconsolidated and undrained shear (UU) and Scanning Electron Microscope (SEM) tests. The results showed that under the same curing time and confining pressure, the shear strength of PURD increased with the increase in WPU content. When the WPU content was 6%, the WPU presented the best reinforcement effect on RA. The failure strain of PURD increased with the increase in confining pressure, but increased first and then reduced with the increase in WPU content. The specimens with 5% WPU content showed the best ductility. At the curing time of 7 and 28 days, the internal friction angle and cohesion of PURD increased with the increase in WPU content, and they reached a maximum when the WPU content was 6%. The internal friction angle barely budged, but the cohesion increased obviously. The enhancement effect of WPU was attributed to the spatial reticular membrane structure produced by wrapping and bonding particles with the WPU film. Microscopic analysis showed that with the increase in WPU content, the internal pore and crack size of PURD gradually decreased. As the WPU content increased, the WPU film became increasingly thicker, which increased the adhesion between WPU and RA particles and made the structure of PURD become increasingly denser.

Introduction Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk.Methods and analysis This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study.Ethics and dissemination The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie–CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation.Trial registration number ChiCTR1800017773.Protocol version November 11, 2020 (Version #5).

Frozen and thawed embryo transfer (FET) is currently widely applied in routine assisted reproductive technology (ART) procedure. It is of great necessity to assess the safety of FET and investigate the long-term effect including glucose metabolism on FET-conceived offspring. The mouse model is a highly efficient method to figure out the relationship between the process of FET and offspring health. In this study, we obtained mouse offspring of natural conception (NC), in vitro fertilization (IVF), and FET. Glucose and insulin tolerance test (GTT/ITT) were performed on both chow fed or high fat diet (HFD) fed offspring to examine the glucose metabolism status. We detected hepatic PI3K/AKT pathway by western blotting and transcriptome status by RNA-sequencing. Impaired glucose tolerance (IGT) and decreased insulin tolerance were occurred in FET conceived male offspring. After challenged with the HFD-fed, male offspring in FET group performed earlier and severer IGT than IVF group. Furthermore, higher HOMA-IR index and higher serum insulin level post glucose injected in FET-chow group suggested the insulin resistance status. The PI3K/AKT signaling pathway, the major pathway of insulin in the liver, were also disrupted in FET group. Transcriptomics of the liver reveals significantly downregulated in glucose metabolic process and insulin resistance in the FET-chow group. In our study, FET-conceived male mouse offspring presented glucose metabolism dysfunction mainly manifesting insulin resistance. The hepatic insulin signaling pathway were in concordance with reduced glycogen synthesis, increased glycolysis and enhanced gluconeogenesis status in FET-conceived male offspring.

For cable-stayed bridges, cables are very important components to maintain the safety of the whole bridge structure. It is well-known that change in cable force reflects the health of the cable-stayed bridge. Therefore, it is necessary to detect and quantify local damage in cables prior to the occurrence of a failure. To this end, an improved residual force algorithm independent of static load vector was proposed in this study. The proposed method mainly makes use of the particularity that only a few coefficients in the residual force and static load vectors are nonzero. By combining two different static loading modes, a new damage indicator vector was defined in the method for damage localization and quantification. Compared with existing static residual force methods, the significant advantage of the proposed algorithm is that the specific value and loading position of the static load are not required in the damage identification process. This special advantage causes this method to not require special static loading, but instead uses any load vehicle. This advantage can make the operation process of structural damage identification based on static tests easier and faster. A single tower cable-stayed bridge structure was used to verify the feasibility of the proposed method in cable damage identification. It was shown that the proposed method successfully identified cable damage, even if the value and loading point of the static load were uncertain.

In order to study the effects of recycled aggregate with different particle gradations and different contents on the mechanical properties of cement soil modified by nano-MgO, unconfined compressive strength and scanning electron microscope (SEM) tests were carried out. The cement content was fixed at 15% and the nano-MgO content was 1.5%. The effects of two ages, three recycled aggregate contents, and three recycled aggregate particle gradations were considered. The test results show that the unconfined compressive strength of natural graded (RA), recycled coarse aggregate (SRA), and recycled fine aggregate (TRA) reached the maximum when the content of recycled aggregate was 20%, and the unconfined compressive strength of SRA was higher than that of TRA and RA. The residual strength of RA and SRA samples first increased and then decreased with the increase in recycled aggregate content, and the residual strength of TRA samples increased gradually with the increase in recycled aggregate content. The variation law of peak strain and peak strength of the three particle graded samples was consistent, and the variation law of brittle failure degree was highly consistent with that of residual strength. When the recycled aggregate content of RA, SRA, and TRA samples was 20%, the deformation resistance and stiffness of the samples were the best. In addition, SRA samples showed the best deformation resistance, followed by TRA samples and, finally, RA samples. The smaller the porosity of the sample, the tighter the sample structure and the stronger the bearing capacity of SRA. The unconfined compressive strength of the WPRA sample was represented by an exponentially negative power function of the porosity.

Women with polycystic ovarian syndrome (PCOS) often have a history of infertility and poor pregnancy outcome. The character of the lower genital tract (LGT) microbiome of these patients is still unknown. We collected both vaginal and cervical canal swabs from 47 PCOS patients (diagnosed by the Rotterdam Criteria) and 50 healthy reproductive-aged controls in this study. Variable regions 3–4 (V3–4) were sequenced and analyzed. Operational taxonomic unit (OTU) abundance was noted for all samples. Taxa that discriminated between PCOS and healthy women was calculated by linear discriminant analysis effect size (LEFSe). Results from 97 paired vaginal and cervical canal samples collected from 97 women [mean age 30 (±4 years)] were available for analysis. Using the Rotterdam Criteria, 47 women were diagnosed with PCOS (PCOS, n = 47; control, n = 50). There was no significant difference between cervical canal microbiome and vaginal microbiome from the same individual, however, Lactobacillus spp. was less abundant in both vaginal and cervical canal microbiome of PCOS patients. Several non-Lactobacillus taxa including Gardnerella_vaginalis_00703mash, Prevotella_9_other, and Mycoplasma hominis, were more abundant in the LGT microbiota of PCOS patients. There is a difference between the microorganism in the LGT of patients with PCOS and healthy reproductive-aged women.

Brain and reproductive organ-expressed protein (BRE) is aberrantly expressed in multiple cancers; however, its expression pattern in human esophageal squamous cell carcinoma (ESCC) and its role in ESCC progression remain unclear. In this study, we aimed to investigate the expression pattern of BRE in human ESCC and its role in ESCC progression. BRE was overexpressed in ESCC tissues compared with that in the adjacent non-tumor tissues. Forced expression of BRE was sufficient to enhance ESCC cell growth by promoting cell cycle progression and anti-apoptosis. Silencing of BRE suppressed these malignant phenotypes of ESCC cells. Mechanistic evaluation revealed that BRE overexpression activated the phosphorylation of AKT, and inhibition of the AKT pathway by MK2206 decreased the BRE-induced cell growth and apoptotic resistance in ESCC cells, highlighting the critical role of AKT signaling in mediating the effects of BRE. Moreover, the effects of BRE on ESCC cell growth and AKT activation were verified in a xenograft model in vivo. The present results show that BRE is overexpressed in ESCC tissues and contributes to the growth of ESCC cells by activating AKT signaling both in vitro and in vivo and provide insight into the role of BRE in AKT signaling and ESCC pathogenesis.

Gas production from multiple coal seams has become common practice in many coal basins around the world. Although gas production rates are typically enhanced, the economic viability of such practice is not well studied. In order to investigate the technical and economic feasibility of multiple coal seams production, reservoir simulation integrated with economics modelling was performed to study the effect of important reservoir properties of the secondary coal seam on production and economic performance using both vertical and horizontal wells. The results demonstrated that multiple seam gas production of using both vertical and horizontal wells have competitive advantage over single layer production under most scenarios. Gas content and permeability of the secondary coal seam are the most important reservoir properties that have impact on the economic feasibility of multiple seam gas production. The comparison of vertical well and horizontal well performance showed that horizontal well is more economically attractive for both single well and gas field. Moreover, wellhead price is the most sensitive to the economic performance, followed by operating costs and government subsidy. Although the results of reservoir simulation combined with economic analysis are subject to assumptions, multiple seam gas production is more likely to maintain profitability compared with single layer production. Keywords: Multiple coal seam, Production simulation, Economic viability, Sensitivity, Coalbed methane

Photothermal treatment (PTT) is a promising strategy to deal with multidrug-resistant bacteria infection and promote tissue regeneration. Previous studies demonstrated that hyperthermia can effectively inhibit the growth of bacteria, whereas mild heat can promote cell proliferation, further accelerating wound healing and bone regeneration. Especially, hydrogels with photothermal properties could achieve remotely controlled drug release. In this review, we introduce a photothermal agent hybrid in hydrogels for a photothermal effect. We also summarize the potential mechanisms of photothermal hydrogels regarding antibacterial action, angiogenesis, and osteogenesis. Furthermore, recent developments in photothermal hydrogels in wound healing and bone regeneration applications are introduced. Finally, future application of photothermal hydrogels is discussed. Hydrogels with photothermal effects provide a new direction for wound healing and bone regeneration, and this review will give a reference for the tissue engineering.

As an important secretory organ, skeletal muscle has drawn attention as a potential target tissue for type 2 diabetic mellitus (T2DM). Recent peptidomics approaches have been applied to identify secreted peptides with potential bioactive. However, comprehensive analysis of the secreted peptides from skeletal muscle tissues of db/db mice and elucidation of their possible roles in insulin resistance remains poorly characterized. Here, we adopted a label-free discovery using liquid chromatography tandem mass spectrometry (LC-MS/MS) technology and identified 63 peptides (42 up-regulated peptides and 21 down-regulated peptides) differentially secreted from cultured skeletal muscle tissues of db/db mice. Analysis of relative molecular mass (Mr), isoelectric point (pI) and distribution of Mr vs pI of differentially secreted peptides presented the general feature. Furthermore, Gene ontology (GO) and pathway analyses for the parent proteins made a comprehensive functional assessment of these differential peptides, indicating the enrichment in glycolysis/gluconeogenesis and striated muscle contraction processes. Intercellular location analysis pointed out most precursor proteins of peptides were cytoplasmic or cytoskeletal. Additionally, cleavage site analysis revealed that Lysine (N-terminal)-Alanine (C-terminal) and Lysine (N-terminal)-Leucine (C-terminal) represents the preferred cleavage sites for identified peptides and proceeding peptides respectively. Mapped to the precursors' sequences, most identified peptides were observed cleaved from creatine kinase m-type (KCRM) and fructose-bisphosphate aldolase A (Aldo A). Based on UniProt and Pfam database for specific domain structure or motif, 44 peptides out of total were positioned in the functional motif or domain from their parent proteins. Using C2C12 myotubes as cell model in vitro, we found several candidate peptides displayed promotive or inhibitory effects on insulin and mitochondrial-related pathways by an autocrine manner. Taken together, this study will encourage us to investigate the biologic functions and the potential regulatory mechanism of these secreted peptides from skeletal muscle tissues, thus representing a promising strategy to treat insulin resistance as well as the associated metabolic disorders.

It is widely recognized that robot-based interventions for autism spectrum disorders (ASD) hold promise, but the question remains as to whether social humanoid robots could facilitate joint attention performance in children with ASD. In this study, responsive joint attention was measured under two conditions in which different agents, a human and a robot, initiated joint attention via video. The participants were 15 children with ASD (mean age: 4.96 ± 1.10 years) and 15 typically developing (TD) children (mean age: 4.53 ± 0.90 years). In addition to analyses of fixation time and gaze transitions, a longest common subsequence approach (LCS) was employed to compare participants’ eye movements to a predefined logical reference sequence. The fixation of TD toward agent’s face was earlier and longer than children with ASD. Moreover, TD showed a greater number of gaze transitions between agent’s face and target, and higher LCS scores than children with ASD. Both groups showed more interests in the robot’s face, but the robot induced a lower proportion of fixation time on the target. Meanwhile participants showed similar gaze transitions and LCS results in both conditions, suggesting that they could follow the logic of the joint attention task induced by the robot as well as human. We have discussed the implications for the effects and applications of social humanoid robots in joint attention interventions.