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Abstract Background To explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function. Methods The expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1. Results The expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195. Conclusions Detection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195.

Abstract Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Abstract As nitrogen analogues of iron‐oxo species, high‐valent iron‐imido species have attracted great interest in the past decades. FeV‐alkylimido species are generally considered to be key reaction intermediates in Fe(III)‐catalyzed C(sp3)─H bond aminations of alkyl azides but remain underexplored. Here, it is reported that iron‐corrole (Cor) complexes can catalyze a wide range of intramolecular C─H amination reactions of alkyl azides to afford a variety of 5‐, 6‐ and 7‐membered N‐heterocycles, including alkaloids and natural product derivatives, with up to 3880 turnover numbers (TONs) and excellent diastereoselectivity (>99:1 d.r.). Mechanistic studies including density functional theory (DFT) calculations and intermolecular hydrogen atom abstraction (HAA) reactions reveal key reactive FeV‐alkylimido intermediates. The [FeV(Cor)(NAd)] (Ad = adamantyl) complex is independently prepared and characterized through electron paramagnetic resonance (EPR), resonance Raman (rR) measurement, and X‐ray photoelectron spectroscopy (XPS). This complex is reactive toward HAA reactions with kinetic isotope effects (KIEs) similar to [Fe(Cor)]‐catalyzed intramolecular C─H amination of alkyl azides.

Presently, integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy. Here, we set the genomic and transcriptomic data as the training population data, using BSLMM, TWAS, and eQTL mapping to prescreen features according to | ^βb|>0, top 1% of phenotypic variation explained (PVE), expression-associated single nucleotide polymorphisms (eSNPs), and egenes (false discovery rate (FDR)

Based on the daily summer precipitation data of 99 national stations in Shaanxi Province and the ERA5 reanalysis data from 1979 to 2021， the temporal and spatial variations of extreme summer precipitation and the corresponding large-scale circulation characteristics in Shaanxi Province were studied， and the water vapor tracking analysis was conducted on the typical regions.The results showed that the extreme summer precipitation in shannxi Province exhibits more in the south and less in the north， with increasing trend in the central part of northern shannxi and the eastern part of Guanzhong.The variation trend of extreme precipitation in northern Shaanxi， Guanzhong and southern Shannxi is 0.36 mm·a-1， 0.35 mm·a-1 and 0.11 mm·a-1 respectively based on REOF analysis.In summer， there are three main paths for water vapor sources that affect Shaanxi Province.The northern branch comes from the high latitude region of Eurasia， the eastern branch comes from inland river basins， and the southern branch comes from the South China Sea and the Bay of Bengal.In addition， the increase of extreme summer precipitation in Shaanxi Province after 2005 was the result of the combined effects of the high， middle， and low-level atmospheric circulation.The enhanced divergence in the high atmosphere is conducive to the upward movement， and the water vapor is more likely to enter the inland due to the westward extension of the west Pacific subtropical high in the middle atmosphere.The anomalous easterly wind in the south side of the Mongolian anticyclone and the anomalous southeast wind in the lower atmosphere are more conducive to the transport of water vapor to the northwest region.

ObjectivesPreeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE.MethodsWe utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.ResultsOur analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p

Several developed vehicle spaces and time headway distribution models in traffic flow theory have been widely used in the literature, reflecting the primary uncertainty in drivers’ car-following movements and explaining the traffic flow stochastic features. Moreover, effective vehicle-to-vehicle (V2V) communication is a key to decentralizing traffic information systems. Accurate vehicle headway distribution estimation will ensure reliable communication and benefit passengers’ safety and comfort. Consider several proposals for headway distribution in the literature; this paper studies the effect of space-headway distribution on information propagation delay in assessing the reliability of the V2V communication networks. We utilize the properties of reliability measurement for headway data by introducing the quasi-maximum likelihood estimator (QMLE) to measure the effects that different headway models have on estimating the parameters of headway distribution in a V2V communication network. The statistical analysis is then applied to the real Next-Generation Simulation (NGSIM) data. It validates the proposed methodology and formulations by measuring the effects of model selection on headway data and information propagation delay on the reliability of the V2V network. The results show that the effect of headway distribution when the vehicle’s transmission range is smaller than the road segmentation is not negligible, especially when cars are very distant. Based on our results, we recommend new metrics based on Kullback–Leibler divergence for model selection of headway data, thereby enhancing the reliability of the V2V network.

Complex traits are widely considered to be the result of a compound regulation of genes, environmental factors, and genotype-by-environment interaction (G × E). The inclusion of G × E in genome-wide association analyses is essential to understand animal environmental adaptations and improve the efficiency of breeding decisions. Here, we systematically investigated the G × E of growth traits (including weaning weight, yearling weight, 18-month body weight, and 24-month body weight) with environmental factors (farm and temperature) using genome-wide genotype-by-environment interaction association studies (GWEIS) with a dataset of 1350 cattle. We validated the robust estimator’s effectiveness in GWEIS and detected 29 independent interacting SNPs with a significance threshold of 1.67 × 10−6, indicating that these SNPs, which do not show main effects in traditional genome-wide association studies (GWAS), may have non-additive effects across genotypes but are obliterated by environmental means. The gene-based analysis using MAGMA identified three genes that overlapped with the GEWIS results exhibiting G × E, namely SMAD2, PALMD, and MECOM. Further, the results of functional exploration in gene-set analysis revealed the bio-mechanisms of how cattle growth responds to environmental changes, such as mitotic or cytokinesis, fatty acid β-oxidation, neurotransmitter activity, gap junction, and keratan sulfate degradation. This study not only reveals novel genetic loci and underlying mechanisms influencing growth traits but also transforms our understanding of environmental adaptation in beef cattle, thereby paving the way for more targeted and efficient breeding strategies.

Abstract Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purβ. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purβ, and highlight the clinical implications of these mechanisms in the pathology of RSA.

Abstract Background Effective screening and treatment have reduced the number of women dying from breast cancer (BC). However, the long-term sequelae of BC treatment and psychosocial factors seriously affect the life quality of BC patients and survivors. Therefore, the discovery and application of targeted biomarkers to improve the functional outcome and life quality of BC patients is necessary. Aims To explore the impact of leptin (LEP)/ leptin receptor (LEPR) expression on occurrence and survival of BC. Methods Totally 132 primary BC and 66 non-BC patients who underwent surgery in department of breast surgery in Shanxi Cancer Hospital from January to October in 2009 were enrolled in this retrospective study. LEP and LEPR were examined in BC tissues, benign breast tissues, para-carcinoma tissues using immunohistochemical staining. Kaplan–Meier curve was generated to test survival time. Results The high level expression of LEP and LEPR in BC tissues were significantly higher than that in benign breast tissues and in para-carcinoma tissues (all P 0.05). Conclusions High LEP/LEPR expression were risk factors for occurrence of BC, but without impact on survival.

Abstract The interaction between trophoblasts, stroma cells, and immune cells at the maternal–fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air–liquid surface culture is developed. PVOs contain cytotrophoblasts that can self‐renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO‐based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta‐originated diseases.

Abstract Background There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. The present study aimed to evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy. Method Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups. Result We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p

Abstract Background Genomic selection (GS) has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes. Besides genome, transcriptome and metabolome information are increasingly considered new sources for GS. Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics. Results We utilized the Cosine kernel to map genomic and transcriptomic data as $${n}\times {n}$$ n × n symmetric matrix (G matrix and T matrix), combined with the best linear unbiased prediction (BLUP) for GS. Here, we defined five kernel-based prediction models: genomic BLUP (GBLUP), transcriptome-BLUP (TBLUP), multi-omics BLUP (MBLUP, $$\boldsymbol M=\mathrm{ratio}\times\boldsymbol G+(1-\mathrm{ratio})\times\boldsymbol T$$ M = ratio × G + ( 1 - ratio ) × T ), multi-omics single-step BLUP (mssBLUP), and weighted multi-omics single-step BLUP (wmssBLUP) to integrate transcribed individuals and genotyped resource population. The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that (1) MBLUP was far preferred to GBLUP (ratio = 1.0), (2) the prediction accuracy of wmssBLUP and mssBLUP had 4.18% and 3.37% average improvement over GBLUP, (3) We also found the accuracy of wmssBLUP increased with the growing proportion of transcribed cattle in the whole resource population. Conclusions We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy. Moreover, wmssBLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement–coagulation–fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

The 3′,5′-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization–deprotection reaction, resulting in a high yield of 3′,5′-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.

Abstract. Objective:. To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta (PA). Methods:. This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. According to the intraoperative findings after delivery, the study population was divided into PA and non-PA groups. We compared the pregnancy outcomes between the two groups, used multivariate logistic regression to analyze the risk factors for placental accreta. Results:. For this study we included 11,074 pregnant women with a history of cesarean section; and of these, 869 cases were in the PA group and 10,205 cases were in the non-PA group. Compared with the non-PA group, the probability of postpartum hemorrhage (236/10,205, 2.31% vs. 283/869, 32.57%), severe postpartum hemorrhage (89/10,205, 0.87% vs. 186/869, 21.75%), diffuse intravascular coagulation (3/10,205, 0.03% vs. 4/869, 0.46%), puerperal infection (33/10,205, 0.32% vs. 12/869, 1.38%), intraoperative bladder injury (1/10,205, 0.01% vs. 16/869, 1.84%), hysterectomy (130/10,205, 1.27% vs. 59/869, 6.79%), and blood transfusion (328/10,205,3.21% vs. 231/869,26.58%) was significantly increased in the PA group (P

Abstract Background The cesarean delivery (CD) rate has been increasing globally. Trial of labor after cesarean delivery (TOLAC) has been used as a key method for the reduction of the CD rate. Little is known, however, about the association between the second-stage duration of TOLAC and adverse maternal and neonatal outcomes. This study evaluated the association between perinatal outcomes and the duration of second-stage labor in women undergoing TOLAC. Methods A 10-year retrospective cohort study was performed at the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2010 and January 2020. Women undergoing TOLAC who reached the second stage of labor were included in this study. Duration of the second stage of labor was examined as a categorical variable (group I:

Background: High salt-diets have become significant threats to human health, resulting in hypertension and cardiovascular diseases. Hypertensive disorders during pregnancy are complicated, since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy. High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development. Therefore, we explored how high-salt diets during pregnancy could affect the offspring. Methods: Rats were divided into three groups and fed with low, normal, and high salt diets. The offspring were separated into three groups after weaning based on dietary salt concentration. The blood pressure and urine protein content of both dams and offspring were measured. To evaluate cardiac function, we used Masson staining and immunodetection to confirm the fibrosis status. Finally, we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide (NO)/cGMP-dependent protein kinase I (PKGI) pathway and the angiotensin receptor. Results: High-salt diets increased blood pressure, and offspring previously exposed to high-salt environments were predisposed to hypertension. High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition (EMT). Under these conditions, the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor (AT1R) was upregulated, though the type-2 angiotensin II receptor (AT2R) had the opposite effect. Conclusion: High-salt diets induce high blood pressure and increase predisposition to hypertension in offspring. They are accompanied by cardiac fibrosis, which could be caused by the activation of NO/PKGI and upregulation of AT1R.

Nitrenium ions are highly electrophilic reactive intermediates of formula R−N−R+, nitrogen analogue of carbenes. Here the authors report the detection of a triplet nitrenium ion using time-resolved spectroscopic methods and ab initio computations, allowing a glimpse at the properties and behavior of this important class of intermediates.

Background Ischemic cardiovascular disease is the leading cause of death worldwide. Current pharmacologic therapy has multiple limitations, and patients remain symptomatic despite maximal medical therapies. Deficiency or inhibition of thymidine phosphorylase (TYMP) in mice reduces thrombosis, suggesting that TYMP could be a novel therapeutic target for patients with acute myocardial infarction (AMI). Methods and Results A mouse AMI model was established by ligation of the left anterior descending coronary artery in C57BL/6J wild‐type and TYMP‐deficient (Tymp−/−) mice. Cardiac function was monitored by echocardiography or Langendorff assay. TYMP‐deficient hearts had lower baseline contractility. However, cardiac function, systolic left ventricle anterior wall thickness, and diastolic wall strain were significantly greater 4 weeks after AMI compared with wild‐type hearts. TYMP deficiency reduced microthrombus formation after AMI. TYMP deficiency did not affect angiogenesis in either normal or infarcted myocardium but increased arteriogenesis post‐AMI. TYMP deficiency enhanced the mobilization of bone marrow stem cells and promoted mesenchymal stem cell (MSC) proliferation, migration, and resistance to inflammation and hypoxia. TYMP deficiency increased the number of larger MSCs and decreased matrix metalloproteinase‐2 expression, resulting in a high homing capability. TYMP deficiency induced constitutive AKT phosphorylation in MSCs but reduced expression of genes associated with retinoid‐interferon‐induced mortality‐19, a molecule that enhances cell death. Inhibition of TYMP with its selective inhibitor, tipiracil, phenocopied TYMP deficiency, improved post‐AMI cardiac function and systolic left ventricle anterior wall thickness, attenuated diastolic stiffness, and reduced infarct size. Conclusions This study demonstrated that TYMP plays an adverse role after AMI. Targeting TYMP may be a novel therapy for patients with AMI.

Abstract Battery electric vehicles (BEVs) have emerged as a promising alternative to traditional internal combustion engine (ICE) vehicles due to benefits in improved fuel economy, lower operating cost, and reduced emission. BEVs use electric motors rather than fossil fuels for propulsion and typically store electric energy in lithium-ion cells. With rising concerns over fossil fuel depletion and the impact of ICE vehicles on the climate, electric mobility is widely considered as the future of sustainable transportation. BEVs promise to drastically reduce greenhouse gas emissions as a result of the transportation sector. However, mass adoption of BEVs faces major barriers due to consumer worries over several important battery-related issues, such as limited range, long charging time, lack of charging stations, and high initial cost. Existing solutions to overcome these barriers, such as building more charging stations, increasing battery capacity, and stationary vehicle-to-vehicle (V2V) charging, often suffer from prohibitive investment costs, incompatibility to existing BEVs, or long travel delays. In this paper, we propose Peer-to-Peer Car Charging (P2C2), a scalable approach for charging BEVs that alleviates the need for elaborate charging infrastructure. The central idea is to enable BEVs to share charge among each other while in motion through coordination with a cloud-based control system. To re-vitalize a BEV fleet, which is continuously in motion, we introduce Mobile Charging Stations (MoCS), which are high-battery-capacity vehicles used to replenish the overall charge in a vehicle network. Unlike existing V2V charging solutions, the charge sharing in P2C2 takes place while the BEVs are in-motion, which aims at minimizing travel time loss. To reduce BEV-to-BEV contact time without increasing manufacturing costs, we propose to use multiple batteries of varying sizes and charge transfer rates. The faster but smaller batteries are used for charge transfer between vehicles, while the slower but larger ones are used for prolonged charge storage. We have designed the overall P2C2 framework and formalized the decision-making process of the cloud-based control system. We have evaluated the effectiveness of P2C2 using a well-characterized simulation platform and observed dramatic improvement in BEV mobility. Additionally, through statistical analysis, we show that a significant reduction in carbon emission is also possible if MoCS can be powered by renewable energy sources.

Locating the genetic variation of important livestock and poultry economic traits is essential for genetic improvement in breeding programs. Identifying the candidate genes for the productive ability of Huaxi cattle was one crucial element for practical breeding. Based on the genotype and phenotype data of 1,478 individuals and the RNA-seq data of 120 individuals contained in 1,478 individuals, we implemented genome-wide association studies (GWAS), transcriptome-wide association studies (TWAS), and Fisher’s combined test (FCT) to identify the candidate genes for the carcass trait, the weight of longissimus dorsi muscle (LDM). The results indicated that GWAS, TWAS, and FCT identified seven candidate genes for LDM altogether: PENK was located by GWAS and FCT, PPAT was located by TWAS and FCT, and XKR4, MTMR3, FGFRL1, DHRS4, and LAP3 were only located by one of the methods. After functional analysis of these candidate genes and referring to the reported studies, we found that they were mainly functional in the progress of the development of the body and the growth of muscle cells. Combining advanced breeding techniques such as gene editing with our study will significantly accelerate the genetic improvement for the future breeding of Huaxi cattle.

Abstract Water holding capacity (WHC) is an important sensory attribute that greatly influences meat quality. However, the molecular mechanism that regulates the beef WHC remains to be elucidated. In this study, the longissimus dorsi (LD) muscles of 49 Chinese Simmental beef cattle were measured for meat quality traits and subjected to RNA sequencing. WHC had significant correlation with 35 kg water loss (r = − 0.99, p

Abstract To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

Abstract Background Our objective was to assess whether modifications to a customized targeted RNA sequencing (RNAseq) assay to include unique molecular identifiers (UMIs) that collapse read counts to their source mRNA counts would improve quantification of transcripts from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples. The assay (SET4) includes signatures that measure hormone receptor and PI3-kinase related transcriptional activity (SETER/PR and PI3Kges), and measures expression of selected activating point mutations and key breast cancer genes. Methods Modifications included steps to introduce eight nucleotides-long UMIs during reverse transcription (RT) in bulk solution, followed by polymerase chain reaction (PCR) of labeled cDNA in droplets, with optimization of the polymerase enzyme and reaction conditions. We used Lin’s concordance correlation coefficient (CCC) to measure concordance, including precision (Rho) and accuracy (Bias), and nonparametric tests (Wilcoxon, Levene’s) to compare the modified (NEW) SET4 assay to the original (OLD) SET4 assay and to whole transcriptome RNAseq using RNA from matched fresh frozen (FF) and FFPE samples from 12 primary breast cancers. Results The modified (NEW) SET4 assay measured single transcripts (p

Abstract Background To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. Methods This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. Results The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25–29, 30–34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12–2.01), placenta previa (aOR, 1.349; 95% CI, 1.07–1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24–3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05–2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21–1.91) in the second cesarean compared with the reference group (aged 25–29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08–2.24), placental abruption (aOR, 6.464, 95% CI, 1.33–31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43–44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95–24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53–12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54–220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54–5.17) compared with the reference group (aged 25–29 years). Conclusions Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Abstract Background As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis. Methods We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array. Results The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM. Conclusions CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.

Abstract. Objective:. To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies. Methods:. This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18–55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR. Results:. In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793) vs. 5.9% (1803/30,336), P

Abstract Background To determine the effects of previous placenta previa on the maternal and neonatal outcomes of the next pregnancy. Methods This 10-year retrospective cohort study was conducted in the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2009 and 2018. We retrospectively analyzed the effects of a previous singleton pregnancy in women with and without placenta previa on the outcomes of the subsequent pregnancy. To control for confounders, we used multiple logistic regression models. Results A total of 57,251 women with singleton pregnancies gave birth during the 10-year study period. Among them, 6070 women had two consecutive births. For the first pregnancy, 1603 women delivered by cesarean delivery and 4467 by vaginal delivery. Among women with a history of cesarean delivery, placenta previa was an independent risk factor for hemorrhage (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [CI]: 1.1–4.62), placenta accreta spectrum (PAS) disorders (aOR: 4.11, 95% CI: 1.68–10.06), and placenta previa (aOR: 6.24, 95% CI: 2.85–13.67) during the subsequent pregnancy. Puerperal infection, blood transfusion, and perinatal outcomes did not significantly differ between women with a history of placenta previa and women without this history. Among women with a history of vaginal delivery, placenta previa increased the risk of PAS disorders (aOR: 5.71, 95% CI: 1.81–18.03) and placenta previa (aOR: 4.14, 95% CI: 1.07–16.04) during the subsequent pregnancy. There was no significant difference between the two groups in terms of hemorrhage, blood transfusion, puerperal infection, and perinatal outcomes. Conclusions Women with a history of placenta previa are at risk for adverse outcomes such as postpartum hemorrhage, PAS disorders, and placenta previa in the subsequent pregnancy.

Preeclampsia is one of the most common severe pregnancy complications in obstetrics, which is considered a placental source disease. However, the mechanisms underlying preeclampsia remain largely unknown. In this study, UPLC-MS/MS-based metabolomic and lipidomic analysis was used to explore the characteristic placental metabolites in preeclampsia. The results revealed that there were significant changes in metabolites between preeclampsia and normotensive placentas. Weighted correlation network analysis (WGCNA) identified the correlation network module of metabolites highly related to preeclampsia and the clinical traits reflecting disease severity. The metabolic perturbations were primarily associated with glycerophospholipid and glutathione metabolism, which might influent membrane structures of organisms and mitochondria function. Using linear models, three metabolites had an area under receiver operating characteristic curves (AUROC) ≥ 0.80 and three lipids had an AUROC ≥ 0.90. Therefore, metabolomics and lipidomics may offer a novel insight for a better understanding of preeclampsia and provide a useful molecular mechanism underlying preeclampsia.

Abstract Background Allergic diseases, such as asthma, dermatitis, rhinitis, and eczema, are highly prevalent in Chinese school children. Environmental factors, including air pollution and automobile exhaust, play an important role in the etiology of these diseases. However, prenatal and neonatal factors, such as gender, maternal diseases during pregnancy, and premature birth, may also be associated with allergic disease occurrence. The objective of this study was to explore prenatal and neonatal factors that are involved in the development of allergic diseases among primary and middle school students in Guangzhou, China. Methods A cross-sectional survey was launched by the Health Promotion Centre for Primary and Secondary Schools of the Guangzhou Municipality in October 2017. All primary and middle school students in Guangzhou were notified to participate in the questionnaire online under the direction of their parents. The results of the physical examination were reported by the schools’ medical department. The results of the questionnaire were collected and analyzed by the researchers. The prevalence of asthma, allergic rhinitis, allergic dermatitis, and eczema was identified. Results Based on reported 183,449 questionnaires and medical records, the data indicate that the sex, birth weight, neonatal feeding type, delivery mode, and students’ father smoking status were significantly associated with the prevalence of all four allergic diseases in primary and middle school children. In further stratified analyses of the children with normal birth weight (2500–4000 g) and without any maternal diseases during pregnancy, the factors of male sex, high birth weight, cesarean delivery, and father smoking status all increased the risk of asthma, dermatitis, rhinitis, and eczema. Also, unlike exclusive breastfeeding, breast plus formula feeding increased these risks, but pure formula feeding had the opposite effect. Conclusion Prenatal and neonatal factors, including male sex, high birth weight, cesarean delivery, only child, and father smoking status are associated with the risks of allergic diseases in school children.

Abstract Background Utilization of RNA sequencing methods to measure gene expression from archival formalin-fixed paraffin-embedded (FFPE) tumor samples in translational research and clinical trials requires reliable interpretation of the impact of pre-analytical variables on the data obtained, particularly the methods used to preserve samples and to purify RNA. Methods Matched tissue samples from 12 breast cancers were fresh frozen (FF) and preserved in RNAlater or fixed in formalin and processed as FFPE tissue. Total RNA was extracted and purified from FF samples using the Qiagen RNeasy kit, and in duplicate from FFPE tissue sections using three different kits (Norgen, Qiagen and Roche). All RNA samples underwent whole transcriptome RNA sequencing (wtRNAseq) and targeted RNA sequencing for 31 transcripts included in a signature of sensitivity to endocrine therapy. We assessed the effect of RNA extraction kit on the reliability of gene expression levels using linear mixed-effects model analysis, concordance correlation coefficient (CCC) and differential analysis. All protein-coding genes in the wtRNAseq and three gene expression signatures for breast cancer were assessed for concordance. Results Despite variable quality of the RNA extracted from FFPE samples by different kits, all had similar concordance of overall gene expression from wtRNAseq between matched FF and FFPE samples (median CCC 0.63–0.66) and between technical replicates (median expression difference 0.13–0.22). More than half of genes were differentially expressed between FF and FFPE, but with low fold change (median |LFC| 0.31–0.34). Two out of three breast cancer signatures studied were highly robust in all samples using any kit, whereas the third signature was similarly discordant irrespective of the kit used. The targeted RNAseq assay was concordant between FFPE and FF samples using any of the kits (CCC 0.91–0.96). Conclusions The selection of kit to purify RNA from FFPE did not influence the overall quality of results from wtRNAseq, thus variable reproducibility of gene signatures probably relates to the reliability of individual gene selected and possibly to the algorithm. Targeted RNAseq showed promising performance for clinical deployment of quantitative assays in breast cancer from FFPE samples, although numerical scores were not identical to those from wtRNAseq and would require calibration.

Depending on excellent prediction ability, machine learning has been considered the most powerful implement to analyze high-throughput sequencing genome data. However, the sophisticated process of tuning hyperparameters tremendously impedes the wider application of machine learning in animal and plant breeding programs. Therefore, we integrated an automatic tuning hyperparameters algorithm, tree-structured Parzen estimator (TPE), with machine learning to simplify the process of using machine learning for genomic prediction. In this study, we applied TPE to optimize the hyperparameters of Kernel ridge regression (KRR) and support vector regression (SVR). To evaluate the performance of TPE, we compared the prediction accuracy of KRR-TPE and SVR-TPE with the genomic best linear unbiased prediction (GBLUP) and KRR-RS, KRR-Grid, SVR-RS, and SVR-Grid, which tuned the hyperparameters of KRR and SVR by using random search (RS) and grid search (Gird) in a simulation dataset and the real datasets. The results indicated that KRR-TPE achieved the most powerful prediction ability considering all populations and was the most convenient. Especially for the Chinese Simmental beef cattle and Loblolly pine populations, the prediction accuracy of KRR-TPE had an 8.73% and 6.08% average improvement compared with GBLUP, respectively. Our study will greatly promote the application of machine learning in GP and further accelerate breeding progress.

Cattle (Bos taurus) is one of the most widely distributed livestock species in the world, and provides us with high-quality milk and meat which have a huge impact on the quality of human life. Therefore, accurate and complete transcriptome and genome annotation are of great value to the research of cattle breeding. In this study, we used error-corrected PacBio single-molecule real-time (SMRT) data to perform whole-transcriptome profiling in cattle. Then, 22.5 Gb of subreads was generated, including 381,423 circular consensus sequences (CCSs), among which 276,295 full-length non-chimeric (FLNC) sequences were identified. After correction by Illumina short reads, we obtained 22,353 error-corrected isoforms. A total of 305 alternative splicing (AS) events and 3,795 alternative polyadenylation (APA) sites were detected by transcriptome structural analysis. Furthermore, we identified 457 novel genes, 120 putative transcription factors (TFs), and 569 novel long non-coding RNAs (lncRNAs). Taken together, this research improves our understanding and provides new insights into the complexity of full-length transcripts in cattle.

The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.

Purely organic ultralong room temperature phosphorescence (URTP) attracts attention but high efficiencies are rarely achieved. Here the authors use ultrafast spectroscopy to investigate a system of 1,8-naphthalic anhydride in organic hosts and reveal that a cluster exciton forms as a transient state before the guest acts as an energy trap for the URTP state.

Molecular systems displaying aggregation-induced emission (AIE) have important biomedical and optoelectronic applications. Here the authors report a further mechanism for AIE, through aromaticity reversal from the ground state to the excited state, in the non-aromatic annulene derivative of cyclooctatetrathiophene.

Molecular motion has attracted a wide range of interest for different applications. Here, the authors develop nanoparticles with internal molecular motion upon near infrared absorption and use the nanoparticles for photoacoustic imaging and demonstrate this application in vivo.

The power and transportation systems are urban interdependent critical infrastructures (CIs). During the post-disaster restoration process, transportation mobility and power restoration process are interdependent, and their functionalities significantly affect other well-beings of other urban CIs. Therefore, to enhance the resilience of urban CIs, successful recovery strategies should promote CI function cooperatively and synergistically to distribute goods and services efficiently. This paper develops an integrative framework that addresses the challenges of enhancing the recovery efficiency of urban power and transportation systems in short-term recovery period. Specifically, the post-storm recovery process is considered as a scheduling problem under the constraints representing crew dispatch, equipment and fuel limit. We propose a new framework for co-optimizing the recovery scheduling of power and transportation systems, respecting precedency requirement and network constraints. The advantages and benefits of co-optimized recovery scheduling are validated in a testing system.

The deletions of the long arm of chromosome 14 involving the 14q24-q32 region have been identified as deletion 14q (del 14q) syndrome, but were rarely reported. The patients with del 14q syndrome are observed a peculiar facial appearance and neurological defects, but the molecular mechanisms were not clear. Here we generated a human iPSC line from the patient’s amniotic fluid cells with 24 Mb deletion in 14q24.3q32.31 which will serve as useful tools for studying the mechanism of del 14q syndrome and the genes involved, which will provide useful basic theory of prenatal diagnosis.

Machine learning (ML) is perhaps the most useful tool for the interpretation of large genomic datasets. However, the performance of a single machine learning method in genomic selection (GS) is currently unsatisfactory. To improve the genomic predictions, we constructed a stacking ensemble learning framework (SELF), integrating three machine learning methods, to predict genomic estimated breeding values (GEBVs). The present study evaluated the prediction ability of SELF by analyzing three real datasets, with different genetic architecture; comparing the prediction accuracy of SELF, base learners, genomic best linear unbiased prediction (GBLUP) and BayesB. For each trait, SELF performed better than base learners, which included support vector regression (SVR), kernel ridge regression (KRR) and elastic net (ENET). The prediction accuracy of SELF was, on average, 7.70% higher than GBLUP in three datasets. Except for the milk fat percentage (MFP) traits, of the German Holstein dairy cattle dataset, SELF was more robust than BayesB in all remaining traits. Therefore, we believed that SEFL has the potential to be promoted to estimate GEBVs in other animals and plants.

Objectives In this cross-sectional survey, we sought to determine the prevalence of and the influence of prenatal and neonatal factors on childhood visual impairment without correction (VIUC) in a paediatric population from Guangzhou, China.Setting The health survey covered 11 administrative districts in Guangzhou, including 991 schools.Participants All of the primary and middle school students in Guangzhou were invited to complete an online questionnaire with the help of their parents. The results of physical examinations were reported by school medical departments. The results of the questionnaire were collected by the researchers. In total, 253 301 questionnaires were collected.Primary outcome measures The students’ uncorrected visual acuity (UCVA) was examined by trained optometrists by standard logarithmic visual acuity charts. VIUC was defined by UCVA (of the better eye) (UCVA

Current vehicle navigation systems usually rely on global real-time traffic information. They suggest the best paths to travelers through an independent and selfish-routing mechanism. Existing studies show that such systems have a great potential to cause traffic congestions oscillating among several alternative corridors, i.e., iteratively leading exceeding traffic into light traffic corridors and making congestion on one and then another within a short time period. To address this issue, this research proposes a local information provision strategy, given travelers are still guided by an independent and selfish-routing mechanism. The coverage of the real-time information provision is identified by the minimum bounding rectangle, and the ellipse method respectively. The benefits of the proposed strategy in system level are investigated by the simulation studies built upon the Borman expressway network. The simulation results indicate that as the local travel time information provision strategy is used, it may save 10–25% of the system travel time resulting from global information provision strategy under medium or high network traffic loads. Moreover, the sensitivity analyses indicate that the merits of the local travel time information provision strategy are more significant as the penetration of smart vehicles increases over the network. Thus, the proposed local information provision strategy outperforms global information provision strategy in system level network performance.

Body weight (BW) is an important longitudinal trait that directly described the growth gain of bovine in production. However, previous genome-wide association study (GWAS) mainly focused on the single-record traits, with less attention paid to longitudinal traits. Compared with traditional GWAS models, the association studies based on the random regression model (GWAS-RRM) have better performance in the control of the false positive rate through considering time-stage effects. In this study, the BW trait data were collected from 808 Chinese Simmental beef cattle aged 0, 6, 12, and 18 months, then we performed a GWAS-RRM to fit the time-varied SNP effect. The results showed a total of 37 significant SNPs were associated with BW. Gene functional annotation and enrichment analysis indicated FGF4, ANGPT4, PLA2G4A, and ITGA5 were promising candidate genes for BW. Moreover, these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. These findings will provide prior molecular information for bovine gene-based selection, as well as facilitate the extensive application of GWAS-RRM in domestic animals.

Semiconductor physics: Energy saving flexible broadband hybrid photodetector Energy efficient and flexible alternative photodetector that detects both visible and invisible light comes closer to real life than ever. A group of researchers from China has developed an organic-inorganic hybrid photodetector that outperforms conventional inorganic like Si and InGaAs-based photodetectors in at least two aspects: broader detection spectral range and much lower dark current. Thanks to the structural flexibility of two hybrid photosensitive materials, methyl-ammonium lead halide and lead phthalocyanine, the team engineered the large area sub-micron thick photodetector with porous structures, which is the key to reducing the standby power consumption by more than 30 times compared to the best InGaAs and Si-based photodetectors. More importantly, the hybrid photodetector needs no additional apparatus or power to cool it for continuous operation, in contrast to the InGaAs photodetector.

Glanzmann thrombasthenia (GT) is a rare monogenic hemorrhagic disorder involving aggregation defect of non-nuclear platelets. In this study we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of a GT patient with complex heterogeneous mutations of ITGA2B gene. GT-iPSCs could be successfully differentiated into platelets (GT-iPS-platelets). GT-iPS-platelets were CD41−/CD42b+/CD61− and were platelet activation marker (PAC-1) negative after adenosine diphosphate (ADP) activation. Furthermore, GT-iPS-platelets were defective in platelet aggregation tests in vitro. Moreover, exogenous expression of the wild-type ITGA2B gene in GT-iPS platelets restored CD41 expression and normal platelet aggregation. Our study suggested that patient-specific iPSCs could be a potential target of stem cell based gene therapy for platelet diseases.

The objective of the present study was to perform a genome-wide association study (GWAS) for growth curve parameters using nonlinear models that fit original weight–age records. In this study, data from 808 Chinese Simmental beef cattle that were weighed at 0, 6, 12, and 18 months of age were used to fit the growth curve. The Gompertz model showed the highest coefficient of determination (R2 = 0.954). The parameters’ mature body weight (A), time-scale parameter (b), and maturity rate (K) were treated as phenotypes for single-trait GWAS and multi-trait GWAS. In total, 9, 49, and 7 significant SNPs associated with A, b, and K were identified by single-trait GWAS; 22 significant single nucleotide polymorphisms (SNPs) were identified by multi-trait GWAS. Among them, we observed several candidate genes, including PLIN3, KCNS3, TMCO1, PRKAG3, ANGPTL2, IGF-1, SHISA9, and STK3, which were previously reported to associate with growth and development. Further research for these candidate genes may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.

Benzoin is one of the most commonly used photoinitiators to induce free radical polymerization. Here, improved benzoin properties could be accomplished by the introduction of two methoxy substituents, leading to the formation of 3’,5’-dimethoxybenzoin (DMB) which has a higher photo-cleavage quantum yield (0.54) than benzoin (0.35). To elucidate the underlying reaction mechanisms of DMB and obtain direct information of the transient species involved, femtosecond transient absorption (fs-TA) and nanosecond transient absorption (ns-TA) spectroscopic experiments in conjunction with density functional theory/time-dependent density functional theory (DFT/TD-DFT) calculations were performed. It was found that the photo-induced α-cleavage (Norrish Type I reaction) of DMB occurred from the nπ* triplet state after a rapid intersystem crossing (ISC) process (7.6 ps), leading to the generation of phenyl radicals on the picosecond time scale. Compared with Benzoin, DMB possesses two methoxy groups which are able to stabilize the alcohol radical and thus result in a stronger driving force for cleavage and a higher quantum yield of photodissociation. Two stable conformations (cis-DMB and trans-DMB) at ground state were found via DFT calculations. The influence of the intramolecular hydrogen bond on the α-cleavage of DMB was elaborated.

Energy issues in transportation systems have garnered increasing attention recently. This study proposes a systematic methodology for policy-makers to minimize energy consumption in multimodal intercity transportation systems considering suppliers’ operational constraints and travelers’ mobility requirements. A bi-level optimization model is developed for this purpose and considers the air, rail, private auto, and transit modes. The upper-level model is a mixed integer nonlinear program aiming to minimize energy consumption subject to transportation suppliers’ operational constraints and traffic demand distribution to paths resulting from the lower-level model. The lower-level model is a linear program seeking to maximize the trip utilities of travelers. The interactions between the multimodal transportation suppliers and intercity traffic demand are considered under the goal of minimizing system energy consumption. The proposed bi-level mixed integer model is relaxed and transformed into a mathematical program with complementarity constraints, and solved using a customized branch-and-bound algorithm. Numerical experiments, conducted using multimodal travel options between Lafayette, Indiana and Washington, D.C. reiterate that shifting traffic demand from private cars to the transit and rail modes significantly reduce energy consumption. Moreover, the proposed methodology provides tools to quantitatively analyze system energy consumption and traffic demand distribution among transportation modes under specific policy instruments. The results illustrate the need to systematically incorporate the interactions among traveler preferences, network structure, and supplier operational schemes to provide policy-makers insights for developing traffic demand shift mechanisms to minimize system energy consumption. Hence, the proposed methodology provide policy-makers the capability to analyze energy consumption in the transportation sector by a holistic approach.

Apoptosis and necrosis of intestinal epithelial cells (IECs), induced by ischemia-reperfusion (I/R) injury, can lead to dysfunction of the intestinal barrier, which could cause multiple organ dysfunction syndromes. Mesenchymal stem cells (MSCs) have the potential of providing protective effects on damaged IECs via paracrine action. This study investigated whether hypoxia can enhance the protective effect of placental-derived MSCs (pMSCs) on H2O2-treated-caco2 cells, and explored the possible mechanism. The pMSCs isolated by tissue culture were fibroblast-like, positive for CD73, CD90 and CD105 and can differentiate into chondrocytes and endothelial cells. Five days after treatment with H2O2, the numbers of living caco2 cells significantly decreased. More live H2O2-treated-caco2 cells were observed in pMSCs hypoxia culture medium (pMSCs-HCM) than pMSCs normoxia culture medium (pMSCs-NCM), and the application of a specific antibody that blocked insulin-like growth factor-1 (IGF-1) leads to a significant decrease of the protective effect of pMSCs-HCM. Hypoxia can promote IGF-1 expression of pMSCs at mRNA and protein levels, and caco2 stably expressed IGF-1 receptor. Knocking down IGF-1 expression in pMSCs by siRNA resulted in a significant attenuation of the increase in apoptosis of H2O2-treated-caco2 cultured in pMSCs-HCM. In conclusion, hypoxia can increase the protective effect of pMSCs on H2O2-treated-caco2 cells via a promotion of their paracrine actions, and the key cytokine involved is IGF-1.