Search

Autophagy-related protein 7 (ATG7) is an essential autophagy effector enzyme. Although it is well known that autophagy plays crucial roles in the infections with various viruses including influenza A virus (IAV), function and underlying mechanism of ATG7 in infection and pathogenesis of IAV remain poorly understood. Here, in vitro studies showed that ATG7 had profound effects on replication of IAV. Depletion of ATG7 markedly attenuated the replication of IAV, whereas overexpression of ATG7 facilitated the viral replication. ATG7 conditional knockout mice were further employed and exhibited significantly resistant to viral infections, as evidenced by a lower degree of tissue injury, slower body weight loss, and better survival, than the wild type animals challenged with either IAV (RNA virus) or pseudorabies virus (DNA virus). Interestingly, we found that ATG7 promoted the replication of IAV in autophagy-dependent and -independent manners, as inhibition of autophagy failed to completely block the upregulation of IAV replication by ATG7. To determine the autophagy-independent mechanism, transcriptome analysis was utilized and demonstrated that ATG7 restrained the production of interferons (IFNs). Loss of ATG7 obviously enhanced the expression of type I and III IFNs in ATG7-depleted cells and mice, whereas overexpression of ATG7 impaired the interferon response to IAV infection. Consistently, our experiments demonstrated that ATG7 significantly suppressed IRF3 activation during the IAV infection. Furthermore, we identified long noncoding RNA (lncRNA) GAPLINC as a critical regulator involved in the promotion of IAV replication by ATG7. Importantly, both inactivation of IRF3 and inhibition of IFN response caused by ATG7 were mediated through control over GAPLINC expression, suggesting that GAPLINC contributes to the suppression of antiviral immunity by ATG7. Together, these results uncover an autophagy-independent mechanism by which ATG7 suppresses host innate immunity and establish a critical role for ATG7/GAPLINC/IRF3 axis in regulating IAV infection and pathogenesis.

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.

Abstract The exchange bias (EB) effect plays an undisputed role in the development of highly sensitive, robust, and high-density spintronic devices in magnetic data storage. However, the weak EB field, low blocking temperature, as well as the lack of modulation methods, seriously limit the application of EB in van der Waals (vdW) spintronic devices. Here, we utilized pressure engineering to tune the vdW spacing of the two-dimensional (2D) FePSe3/Fe3GeTe2 heterostructures. The EB field (H EB, from 29.2 mT to 111.2 mT) and blocking temperature (T b, from 20 K to 110 K) are significantly enhanced, and a highly sensitive and robust spin valve is demonstrated. Interestingly, this enhancement of the EB effect was extended to exposed Fe3GeTe2, due to the single-domain nature of Fe3GeTe2. Our findings provide opportunities for the producing, exploring, and tuning of magnetic vdW heterostructures with strong interlayer coupling, thereby enabling customized 2D spintronic devices in the future.

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

Abstract Water inrush through karst collapse column is one of the great disasters which threaten coal mine safety production. The particle size distribution of karst collapse column is one of its most basic physical properties, which has a strong correlation with particle migration, and is an important basis for evaluating the water inrush risk of collapse column. The nonlinear flow tests of broken rock under different gradation conditions were carried out by a custom-built apparatus, and the relationship equation between nonlinear flow parameters (permeability and non-Darcy factor) and Talbol power exponent n were constructed. A nonlinear flow model with variable mass of water inrush from karst collapse column was established. The spatio-temporal evolution law of pressure, velocity, porosity and concentration under particle loss and the influence of particle gradation on the water inrush risk of karst collapse column at Fan gezhuang mine were discussed. During the water inrush, the flow state of fluids in karst collapse column gradually transitions from a weak inertial flow to a strong one, eventually becoming a turbulent flow. The flow model based on single flow state cannot reflect the essence of flow regime transition in water inrush. The larger n is, the stronger the water permeability of the karst collapse column, the faster the particles migrate and are lost, the faster the flow channel with high porosity develops, the shorter the time for the water inflow to reach its peak value, and the greater the risk of water inrush.

Abstract Background Luteinizing hormone (LH) is critical in follicle growth and oocyte maturation. However, the value of recombinant LH (r-LH) supplementation to recombinant follicle stimulating hormone (r-FSH) during controlled ovarian stimulation in the gonadotrophin releasing hormone (GnRH) antagonist regimen is controversial. Methods This multicenter retrospective cohort study recruited 899 GnRH antagonist cycles stimulated with r-LH and r-FSH in 3 reproductive centers and matched them to 2652 r-FSH stimulating cycles using propensity score matching (PSM) for potential confounders in a 1:3 ratio. The primary outcome was the cumulative live birth rate (CLBR) per complete cycle. Results The baseline characteristics were comparable in the r-FSH/r-LH and r-FSH groups after PSM. The r-FSH/r-LH group achieved a higher CLBR than the r-FSH group (66.95% vs. 61.16%, p = 0.006). R-LH supplementation also resulted in a higher 2-pronuclear embryo rate, usable embryo rate, and live birth rate in both fresh embryo transfer cycles and frozen-thawed embryo transfer (FET) cycles. No significant differences were found in the rate of moderate and severe ovarian hyperstimulation syndrome (OHSS), or cycle cancellation rate in the prevention of OHSS. Conclusions R-LH supplementation to r-FSH in the GnRH antagonist protocol was significantly associated with a higher CLBR and live birth rate in fresh and FET cycles, and improved embryo quality without increasing the OHSS rate and cycle cancellation rate.

Abstract The fault-crossing tunnel in high geothermal areas can be severely damaged under strong earthquake. In this paper, numerical models were established in Flac3d to investigate the thermal insulation and seismic effects under the strong earthquake when using highly damped composite structure. The results showed that the thermal insulation effect of the PC, the PC highly damped composite structure and the SFRC highly damped composite structure were almost the same, which the PC highly damped composite structure was slightly better. After applying the highly damped composite structure, the maximum and minimum principal stresses on the lining decreased, it showed that highly damped composite structure could enhance the seismic effect of tunnel. The safety factor of SFRC highly damped composite structure was 2.420, which was a 28.14% increase compared to PC. Based on numerical simulations, the thermal insulation and seismic effect of SFRC highly damped composite structure was better than other seismic measures. The research can provide a reference for the design of thermal insulation and anti-earthquake for fault-crossing tunnel under strong earthquake in high geothermal area.

Research question: Does glycan profile in spent blastocyst culture medium have the potential to be used as a biomarker to predict implantation outcome. Design: A nested case-control study was conducted in Northwest women’s and children’s Hospital, Xi’an, China. The patients underwent fresh IVF/ICSI cycles with single blastocyst transfer were included. Total 78 cases were included and separated into groups according to success (n = 39) and failure (n = 39) implantation outcomes. The glycosylation patterns in spent blastocyst culture medium were detected by lectin microarray containing 37 lectins using pooled samples and confirmed by reversed lectin microarray using individual sample. Results: Binding signals of 10 lectins were found to be different between samples from successful and failed implantation. And 8 of them were confirmed that glycans binding to lectin NPA, UEA-I, MAL-I, LCA and GNA were significantly increased while DBA and BPL were decreased in the successful implantation compared to failed implantation. The glycan binding to lectin PHA-E + L had no difference between two groups. No significant differences in the glycan profile were found in spent culture medium of embryos with different morphological grades except the glycan binding to UEA-I between blastocysts of Poor and blastocysts of Medium. Conclusion: Detection of glycan profile in spent culture medium may lead to a novel non-invasive assessment assay of embryo viability. In addition, these results may be helpful to further understanding molecular mechanisms in embryo implantation.

During the operation of cooling water pumps, it is necessary to operate them under conditions of low flow rate. In order to improve the unstable performance of the cooling water pump under low flow rate conditions. Taking the cooling water pump as the research object, the internal flow and pressure pulsation characteristics of the cooling water pump under 0.4Q to 0.6Q conditions were investigated, and the influence of different operating conditions on the performance and vibration of the cooling water pump was analyzed. The ANSYS CFX 2022 software and the SST k-ω turbulence model were used to perform a three-dimensional numerical simulation of the cooling water pump. After analyzing the simulation results, the velocity and pressure cloud and streamline diagram within the semi-spiral suction casing and impeller were obtained. The internal flow state of the cooling water pump was then analyzed in detail under low flow rate conditions. At the same time, a series of monitoring points were set up within the impeller, and the pressure pulsation within the impeller was analyzed using the frequency domain diagram and the radial force polar coordinate diagram. The results show that at flow rates between 0.4Q and 0.6Q, a certain amount of vortex has been generated in the suction casing, which affects the flow state when entering the impeller. Furthermore, significant vortices have been generated in the middle and back part of the blade and mainly concentrated in the pump cover of the mid-open pump. At the same time, when in low flow rate conditions, the primary frequency of pressure pulsation is mainly the axial frequency, with three times the axial frequency and blade frequency following. The amplitude of the pressure surface (PS) of the blade is greater than that of the suction surface (SS) and increases as the flow rate decreases. The internal radial force corresponds with the result of pressure pulsation and exhibits a certain pattern. This study outlines the coolant pump’s internal flow and pressure pulsation characteristics under low-flow conditions. It proposes a solution to stabilize the cooling water pump at low flow rates and provides theoretical guidance for optimizing its design.

To investigate the transient characteristics of high-speed axial flow water-jet pumps during start-up and emergency acceleration as well as to analyze how different accelerations affect the performance of internal flow, the k–ω turbulence model of the SST model and Zwart cavitation model were used to perform unsteady simulation on an impeller rotating at a speed of 1850. The steady-state numerical simulation method was verified by the experimental data, the numerical calculation results were basically consistent with the experimental data, the margin of error was within 5%, and the numerical simulation method was reliable. The results show that there was an obvious transient effect in the process of variable speed, and the thrust reached a stable state later than the speed. The buffer times for start-up times of 1 s, 2 s, and 3 s were 0.0394 s, 0.0375 s, and 0.0282 s, respectively, and the buffer times for the acceleration times of 0.5 s, 1.0 s, and 1.5 s were 0.0330 s, 0.0273 s, and 0.0230 s, respectively. The greater the acceleration, the more serious the flow rate and thrust lag behind the speed, and the greater the impact thrust. Under the same acceleration, the buffer time required in the start-up process was 19.3~22.6% longer than that in the acceleration process. During the change in speed of the high-speed water-jet pump, the vortex core area of the suction surface (SS) first appeared on the side of the shroud at the inlet, increased with the increase in the rotational speed, and developed toward the middle of the impeller. However, after the flow was stabilized, the vortex core region gradually shrank and eventually disappeared. When the rotational speed reached 0.6 times the design speed, cavitation occurred at the leading edge (LE) of the blade, and the cavitation area increased with the increase in the rotational speed. When reaching the same speed, the greater the acceleration, the more serious the cavitation. Under the design speed, that is, 6000 r/min, the cavitation volume fraction of the 1 s start-up process was 7.32%, the 2 s start-up process was 5.84%, the 3 s start-up process was 5.32%, and the 0.5 s acceleration process was 6.86%. The cavitation volume fraction of the 1 s acceleration process was 5.04%, and that of the 1.5 s acceleration process was 4.23%. Under the same acceleration, the cavitation volume fraction of the start-up process was 6.7~25% larger than that of the acceleration process. Compared with the start-up process and acceleration process under the same acceleration, the accelerated process had a smaller region of vortex core, stronger anti-cavitation ability, and more stable flow than the start-up process. During the actual operation process of the water-jet pump, it is advisable to use smaller accelerations and segmented accelerations as much as possible until the design speed is reached. The research findings serve as a foundation for future investigations into the transient characteristics of high-speed water-jet pumps operating under variable speed conditions.

IntroductionIn frozen-thawed embryo transfer (FET) cycles, hormone replacement treatment (HRT) was associated with a higher risk of hypertensive disorders of pregnancy (HDP) compared with natural cycles (NC). Multiple pregnancy was a risk factor for HDP and several studies did not conduct subgroup analysis of singleton pregnancy and multiple pregnancy.ObjectiveTo investigate whether HRT regimen could be a risk factor for HDP in women undergoing FET cycles in singleton and twin pregnancies.MethodsA retrospective cohort study at a tertiary hospital, including a total of 9120 women who underwent FET and achieved ongoing pregnancy; 7590 patients underwent HRT-FET and 1530 NC-FET. The main outcome was HDP. HDP were analyzed for singleton and twin pregnancies, respectively.ResultsIn the singleton pregnancy, the risk of HDP in the HRT-FET group was significantly higher than that in the NC-FET group (6.21% vs. 4.09%; P=0.003). After adjusting for female age oocyte pick up, female age at FET and body mass index (BMI), HRT was found as a risk factor for HDP (adjusted odds ration [aOR]: 1.43; 95% confidence interval [CI]: 1.07 to 1.91; P=0.017). In the multiple pregnancy, the risk of HDP in the HRT-FET and NC-FET groups was similar.ConclusionHRT was associated with a higher risk of HDP in women who underwent FET and achieved singleton pregnancy.

Aiming at the damage evolution and energy release characteristics of sandstone in failure process, uniaxial and cyclic loading experiments were conducted with the average temperature, infrared temperature field, acoustic emission (AE), and displacement field being monitored simultaneously. The results show that in the low stress stage, the initial pores and fissures are compressed and the thermoelastic effect is insignificant. At the same time, the AE events are active, but most of the events are released with low energy. Then, the surface of the specimen shows stratified displacement phenomenon in the vertical direction. In the following stage, the thermoelastic effect is significant, and the average temperature of specimens shows a linear correlation with stress, whereas the AE is relatively inactive, and vertical surface deformation shows further homogenization and saliency. Because of the top and bottom constraints, the horizontal displacement field shows axis symmetrical distribution of double half-ellipse like a drum. During the yielding phase and the rupture moment, the average temperature rises obviously because of the heat from the friction of the rupture surface, and the temperature field also appears the phenomenon of differentiation; in the meantime, a large amount of AE events occur and the proportion of high energy events increases; further, the deformation field is significantly gathered near the ruptured position. Finally, the time sequence of the multiple physical parameters (AE parameters, average temperature, temperature fields, horizontal and vertical displacement fields) is summarized, which can be a reference for the stress state and failure analysis.

To elucidate the role of post-translational modifications (PTMs) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein’s structure and virulence, we generated a high-resolution map of 87 PTMs using liquid chromatography with tandem mass spectrometry data on the extracted spike protein from SARS-CoV-2 virions and then reconstituted its structure heterogeneity caused by PTMs. Nonetheless, Alphafold2, a high-accuracy artificial intelligence tool to perform protein structure prediction, relies solely on primary amino acid sequence, whereas the impact of PTM, which often modulates critical protein structure and function, is much ignored. To overcome this challenge, we proposed the mutagenesis approach—an in silico, site-directed amino acid substitution to mimic the influence of PTMs on protein structure due to altered physicochemical properties in the post-translationally modified amino acids—and then reconstituted the spike protein’s structure from the substituted sequences by Alphafold2. For the first time, the proposed method revealed predicted protein structures resulting from PTMs, a problem that Alphafold2 has yet to address. As an example, we performed computational analyses of the interaction of the post-translationally modified spike protein with its host factors such as angiotensin-converting enzyme 2 to illuminate binding affinity. Mechanistically, this study suggested the structural analysis of post-translationally modified protein via mutagenesis and deep learning. To summarize, the reconstructed spike protein structures showed that specific PTMs can be used to modulate host factor binding, guide antibody design, and pave the way for new therapeutic targets. The code and Supplementary Materials are freely available at https://github.com/LTZHKUSTGZ/SARS-CoV-2-spike-protein-PTM.

BackgroundDay 5 (D5) blastocysts are generally given priority to transfer than day 6 (D6) blastocysts; however, which one should be prioritized to transfer when only low-grade D5 and high-grade D6 blastocysts are available?MethodsA large retrospective cohort study was carried out to evaluate the live birth rate (LBR) following D5 and D6 blastocysts in single frozen-thawed blastocyst transfer (FBT) during January 2014 and December 2018. A multivariate logistic regression was conducted to evaluate the combined impact of expansion day (D5 and D6) and blastocyst quality (high grade/low grade) on LBR, accounting for the potential confounding factors. The biopsied blastocysts from a consecutive PGT-A case series during February 2013 to December 2021 were analyzed in a supplementary study.ResultsThe LBR achieved in high-grade D6 blastocyst transfer was significantly higher than that in low-grade D5 blastocyst transfer (50.43% vs. 40.70%, aOR 1.54, 95% CI 1.05–2.26, p = 0.027). There were no significant differences in preterm birth rate, very preterm birth rate, mean live birth weight, and birth weight 4,000 g between the two cohorts. As for aneuploidy analysis in PGT, there were 54.55% of euploid blastocysts (30/55) among high-grade D6 blastocysts, significantly higher than the 41.39% of euploid blastocysts (565/1,365) among low-grade D5 blastocysts (p < 0.001).ConclusionsOur data suggest that D6 blastocysts with high morphology grading are preferred than D5 blastocysts with low morphology grading when selecting blastocyst transfer to shorten the time of conception.

Pump-jet propellers are currently the mainstream propulsion method for underwater vehicles, and cavitation is an important factor limiting the high speed and miniaturization of pump-jet propellers. In order to explore the cavitation performance of high-speed pump-jet propellers, based on the modified SST turbulence model and the Zwart cavitation model, a three-dimensional numerical simulation of unsteady internal cavitation flow was carried out by comparing the impeller with specific speed ns = 1920 using FLUENT 2020R2 software. At the same time, the occurrence and development process of cavitation under 0.95 Q, 1.0 Q, and 1.05 Q conditions were analyzed (Q is the mass flow), the changes in gas volume fraction in the impeller channel were captured, the distribution characteristics of cavitation under different NPSH values were explored, and the change law of cavitation with time was determined. The results show that, when NPSH dropped to 95 m, the impeller cavitation first occurred under the 1.05 Q operating condition, and the impeller cavitation volume fraction was 0.0379525. When NPSH dropped to 85 m, the impeller cavitation occurred under the 1.0 Q operating condition, and the impeller cavitation volume fraction was 0.0185164. When NPSH dropped to 80 m, the impeller cavitation occurred under the condition of 0.95 Q, and the volume fraction of the impeller cavitation was 0.013541. The high-speed pump-jet propeller had better anti-cavitation ability with a small flow rate. The cavitation distribution law under the three operating conditions was similar; cavitation was first generated on the impeller inlet edge and near the shroud, and the vacuoles with large volumes were mostly concentrated on the impeller inlet side. As the NPSH gradually decreased, the entire flow channel was gradually occupied by vacuoles. As the flow decreased, the corresponding NPSH also decreased. When NPSH dropped to 50 m, the volume fraction of the impeller under all three operating conditions reached around 0.4. As the cavitation only occurred on the suction surface, the volume fraction of the cavitation on the suction surface exceeded 0.8, at which time the impeller had already undergone severe cavitation. Within a complete cycle, bubbles first appeared at the inlet edge of the impeller (measured near the shroud) and gradually spread toward the middle and rear of the impeller, ultimately covering the suction surface of the impeller. Under the design condition, the experimental results of the model pump were consistent with the numerical simulation results, and the error was only 2.68%, thus verifying the reliability of the numerical simulation. The research results provide a reference for the in-depth study of the cavitation performance of high-speed pump-jet propellers and provide a good theoretical basis and practical significance in the engineering field for the high-speed and miniaturization process of high-speed pump-jet propellers.

Evidence shows that neighborhood parks play an important role in serving nearby residents, such as promoting physical activity and relieving stress, but thus far, little attention has been given to the impact of time on park use. This study explored users’ behavioral patterns at different time periods and their perception of attributes during the nighttime in three neighborhood parks in Nanjing, China. A total of 7482 park users were documented using the method of behavior mapping, and the results revealed that the spatial clusters of hotspots for the locations of the observed users differed significantly between late afternoon and evening, and the nighttime park users were more in number and were more active in physical activity. This study also found that improvements in site diversity and incorporations of night markets and shows were emphasized by park users based on their nighttime experience. The findings can be used to improve the future design and management of neighborhood parks, especially for promoting nighttime use.

BackgroundA number of studies have compared the clinical outcomes between the two endometrial preparation methods: natural cycles (NCs) and hormone replacement treatment (HRT) before frozen embryo transfer, but the results were conflicting. In order to mitigate the potential effect of embryos per se, several researchers have worked on this subject for euploid blastocyst transfer, but the results were still inconsistent. Therefore, the present study was aimed to investigate the clinical outcomes between HRT and NC for autologous single vitrified–warmed euploid blastocyst transfer based on our data.MethodsA total of 598 frozen-thawed single euploid blastocyst transfer cycles in the assisted reproductive center of Northwest Women’s and Children’s Hospital from January 2014 to May 2021 were retrospectively analyzed. Women were stratified into the NC (n = 125) or HRT (n = 473) group according to the patient’s preference and the physician’s guidance. Multivariate regression models and subgroup analysis were constructed to analyze the association between endometrial preparation and live birth.ResultsWomen in the NC group had a higher live birth rate (68.80% versus 58.35%, P = 0.034) and a lower risk of total pregnancy loss (8.51% versus 21.14%, P = 0.005) when compared with women in the HRT group. The biochemical pregnancy rate (75.20% versus 74.00%, P = 0.784) and clinical pregnancy rate (74.40% versus 69.98%, P = 0.334) were similar between the two groups (NC versus HRT). NC was associated with an increased odds of live birth compared with HRT by different multivariable analysis models (Model 1: adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.57, 0.36 - 0.90; Model 2: aOR, 95%CI: 0.57, 0.35 - 0.92). In addition, the increased chance of live birth in the NC group was found in all subgroups. No major obstetrical complications and two malformation livebirths were reported.ConclusionsIn women undergoing single euploid frozen blastocyst transfers, the NC group was associated with a lower pregnancy loss rate and an ultimately higher live birth rate than the HRT group. Although HRT is convenient for both clinicians and patients, the lower live birth rate should be taken into account and NC might be the first choice of endometrial preparation method.

Research Question: How to prevent the transfer of a mutation causing osteogenesis imperfecta (OI) to offspring in a couple with recurrent adverse pregnancy outcomes, when the male partner is a gonosomal mosaic carrier.Design: High-throughput sequencing and first-generation DNA sequencing were performed using the tissues from an aborted fetus and its parents. Regions 2 Mb upstream and downstream of the COL1A1 gene were subjected to multiplex PCR to identify single nucleotide polymorphisms (SNPs) and family haplotypes associated with the disease-causing mutation. Single-cell whole-genome amplification and sequencing were performed on trophoblasts cultured in vitro for 5–6 days to construct embryonic SNP haplotypes, and first-generation sequencing was used for pathogenic locus verification and aneuploidy screening. Preimplantation genetic testing for monogenic disorders (PGT-M) was also performed.Results: The aborted fetus was heterozygous for the COL1A1 mutation c.1454G>A (chr17-48272089, p.Gly485Asp) suspected to cause OI. The variant was also detected in the peripheral blood cells and sperm of the male partner, who appeared to be a gonosomal mosaic carrier of the mutation. Three morphologically usable blastocysts were obtained in vitro and successfully expanded after a trophectoderm biopsy. Two blastocysts were unusable owing to aneuploidy; however, one was euploid and did not carry the paternal mutation. Post-transfer gestation was confirmed by systematic B-scan ultrasound, and amniocentesis findings were consistent with the PGT-M results.Conclusion: Parental gonadal mosaicism was the cause of recurrent terminated pregnancies due to fetal skeletal dysplasia. Using PGT-M to select embryos without the paternal pathogenic mutation prevented the vertical transmission of OI in this family, and a successful pregnancy was achieved.

ObjectivePredictive models of the cumulative live birth (CLB) in women undergoing in vitro fertilization (IVF) treatment are limited. The aim of this study was to develop and validate a nomogram for the CLB in women undergoing the first IVF cycle.MethodsBased on a cross-sectional study in assisted reproduction center of Northwest Women’s and Children’s Hospital, 26,689 Chinese patients who underwent IVF treatment was used to develop and validate a prediction model for the CLB. Among those participants, 70% were randomly assigned to the training set (18,601 patients), while the remaining 30% were assigned to the validation set (8,088 patients). A nomogram was constructed based on the results of the multivariate logistic regression analysis. The model performance was evaluated using the C statistic and the calibration performance was assessed by Hosmer-Lemeshow (HL) χ2 statistics and calibration plots.ResultsMultivariate logistic regression analyses revealed that female age, female body mass index (BMI), tubal factor infertility, male infertility, uterine factor infertility, unexplained infertility, antral follicle count (AFC) and basal serum follicle stimulating hormone (FSH) were significant factors for CLB in women undergoing the first IVF cycle. An area under the receiver operating characteristic curve (AUC) in the prediction model was 0.676 (95% CI 0.668 to 0.684) in the training group. The validation set showed possibly helpful discrimination with an AUC of 0.672 (95% CI 0.660 to 0.684). Additionally, the prediction model had a good calibration (HL χ2 = 8.240, P=0.410).ConclusionsWe developed and validated a nomogram to predict CLB in women undergoing the first IVF cycle using a single center database in China. The validated nomogram to predict CLB could be a potential tool for IVF counselling.

BackgroundRecent studies have demonstrated that both blastocoel fluid (BF) and spent cell culture media (SCM) have potential as materials for non-invasive or less-invasive pre-implantation genetic analysis. BF may allow more opportunity to obtain cell-free DNA from the inner cell mass (ICM), and it has a lower risk of containing contaminant DNA from cumulus cells, sperm and culture media. There are no data regarding the ICM as a gold standard to evaluate the chromosome constitution of BF or SCM for embryo liquid biopsy.MethodsTwo hundred eighteen donated human blastocysts were warmed and cultured in blastocyst culture media for 18–24 h. The corresponding SCM was collected, and only clear ICM was biopsied in blastocysts; otherwise, the whole blastocyst (WB) was biopsied. Quantitative PCR was performed to determine the DNA levels in the SCM and BF before and after amplification. ChromInst was used to amplify BF/SCM and blastocyst DNA before sequencing. Chromosomal copy number variation (CNV) was investigated to evaluate the chromosome constitution.ResultsIn total, 212 blastocysts were available for SCM and BF collection. The technical success rates (next-generation sequencing data) were 100 and 69.8% (148/212) for SCM and BF, respectively. Among the 148 blastocysts with both SCM and BF data, 101 were euploid and 47 were aneuploid based on ICM (n = 89) or WB (n = 59) analysis as the gold standard. Among all blastocysts, SCM was comparable to BF [specificity: 80.2 versus 61.4% (P = 0.005, χ2 test); sensitivity: 91.5 versus 87.2% (P = 0.738, χ2 test); negative predictive value (NPV): 95.3 versus 91.2% (P = 0.487, χ2 test); positive predictive value (PPV): 68.3% versus 51.3% (P = 0.042, χ2 test)]. The SCM and BF samples were 83.8% (124/148) and 69.6% (103/148) concordant with the corresponding ICM/WB samples when only two categories, euploid or aneuploid/mosaic, were grouped to calculate the concordance.ConclusionsCompared with BF, SCM has superior diagnostic performance, and it is non-invasive for embryos.Clinical Trial Registration[http://www.chictr.org.cn], identifier [ChiCTR-BPD-17014087].

Coral concrete made of coral sand/aggregates has attracted significant interest in the construction of coastal or artificial island buildings by saving significant economic and environmental costs for transporting the conventional building materials from mainland. However, the application of coral concrete is very limited due to the drawback such as low strength, brittleness, and high porosity. This paper develops a new coral concrete composite utilizing coral debris to replace sand and aggregates, sea water, supplementary cementitious waste materials, namely, fly ash and silica fume and modified polypropylene fiber (MPPF) to achieve both sustainable and economic development needs in coastal and island building and construction. The mechanical and durability of the new coral concrete are evaluated and the synergistic effects of fly ash and silica fume on the performance of MPPF coral concrete are discussed. It has been found out that the addition of fly ash and silica fume in MPPF coral concrete can significantly improve the strengths and reduce the chloride diffusion of coral concrete. Compared with those from the specimens without fly ash and silica fume, the compressive, splitting tensile, flexural strengths of MPPF concrete with 10% fly ash and 10% silica fume are improved by 31%, 33%, and 58%, respectively. The new coral concrete composite would be an ideal building material solution for coastal and artificial island applications as most of the materials come from the local wastes.

Abstract Climate change poses a serious threat to biodiversity. Predicting the effects of climate change on the distribution of a species' habitat can help humans address the potential threats which may change the scope and distribution of species. Pterocarya stenoptera is a common fast‐growing tree species often used in the ecological restoration of riverbanks and alpine forests in central and eastern China. Until now, the characteristics of the distribution of this species' habitat are poorly known as are the environmental factors that influence its preferred habitat. In the present study, the Maximum Entropy Modeling (Maxent) algorithm and the Genetic Algorithm for Ruleset Production (GARP) were used to establish the models for the potential distribution of this species by selecting 236 sites with known occurrences and 14 environmental variables. The results indicate that both models have good predictive power. Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. According to the models, the temperate and subtropical regions of eastern China had high environmental suitability for this species, where the species had been recorded. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically to the north and higher elevation. GARP predicted a more conservative expansion. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.

Summary: The diffuse-type gastric cancer (DGC) constitutes a subgroup of gastric cancer with poor prognosis and no effective molecular therapies. Here, we report a phosphoproteomic landscape of DGC derived from 83 tumors together with their nearby tissues. Based on phosphorylation, DGC could be classified into three molecular subtypes with distinct overall survival (OS) and chemosensitivity. We identified 16 kinases whose activities were associated with poor OS. These activated kinases covered several cancer hallmark pathways, with the MTOR signaling network being the most frequently activated. We proposed a patient-specific strategy based on the hierarchy of clinically actionable kinases for prioritization of kinases for further clinical evaluation. Our global data analysis indicates that in addition to finding activated kinase pathways in DGC, large-scale phosphoproteomics could be used to classify DGCs into subtypes that are associated with distinct clinical outcomes as well as nomination of kinase targets that may be inhibited for cancer treatments. : Biological Sciences; Cancer Systems Biology; Proteomics; Systems Biology Subject Areas: Biological Sciences, Cancer Systems Biology, Proteomics, Systems Biology

The Hidden Number Problem (HNP) was introduced by Boneh and Venkastesan to analyze the bit-security of the Diffie–Hellman key exchange scheme. It is often used to mount a side-channel attack on (EC)DSA. The hardness of HNP is mainly determined by the number of nonce leakage bits and the size of the modulus. With the development of lattice reduction algorithms and lattice sieving, the range of practically vulnerable parameters are extended further. However, 1-bit leakage is still believed to be challenging for lattice attacks. In this paper, we proposed an asymmetric lattice sieving algorithm that can solve HNP with 1-bit leakage. The algorithm is composed of a BKZ pre-processing and a sieving step. The novel part of our lattice sieving algorithm is that the lattice used in these two steps have different dimensions. In particular, in the BKZ step we use more samples to derive a better lattice basis, while we just use truncated lattice basis for the lattice sieving step. To verify our algorithm, we use it to solve HNP with 1-bit leakage and 116-bit modulus.

ObjectiveTo investigate the association between pre-pregnancy body mass index (BMI) and miscarriages in women who required assisted reproductive technology (ART) for conception.MethodsA retrospective cohort study was conducted using a 10-year (2006–2015) sample of 14,994 pregnancy cycles with ART treatment in Northwest Women’s and Children’s Hospital, Xi’an, China. The effects of women’s BMI before pregnancy on early miscarriage and miscarriage were assessed using generalized estimating equation models.ResultsThe risks of early miscarriage and miscarriage were higher in the obese group than in the normal weight group [early miscarriage: relative risk (RR) = 1.36, confidence interval (CI): 1.12–1.65; miscarriage: RR = 1.40, 95% CI: 1.17–1.68]. Pre-pregnancy underweight was not associated with an increased risk of early miscarriage or miscarriage. We observed interactions between pre-pregnancy BMI and singleton or twin pregnancy in early miscarriage and miscarriage (P = 0.017 and P = 0.003, respectively). Twin pregnancy increased the effects of pre-pregnancy BMI on early miscarriage and miscarriage (early miscarriage: a. singleton pregnancy: RR = 1.02, 95% CI: 1.01–1.04; b. twin pregnancy: RR = 1.08, 95% CI: 1.03–1.13; miscarriage: a. singleton pregnancy: RR = 1.02, 95% CI: 1.01–1.04; b. twin pregnancy: RR = 1.08, 95% CI: 1.05–1.13).ConclusionsPre-pregnancy obesity was associated with higher risks of early miscarriage and miscarriage in the ART population, and twin pregnancy increased the effects of pre-pregnancy BMI on early miscarriage and miscarriage. Women should maintain a normal BMI before ART initiation to prevent adverse pregnancy outcomes.

Objective: To investigate the mental health of women undergoing assisted reproductive technology (ART) treatment during the novel coronavirus pneumonia (COVID-19) pandemic outbreak in Xi'an, China.Methods: A repeated cross-sectional study was administered to women undergoing ART treatment during the outbreak period (599 women in February 2020) and the control period (892 women in May 2020) at the Northwest Women's and Children's Hospital, Xi'an, China.Results: Both the ART-treated women surveyed during the outbreak period and those surveyed during the control period had high scores on the fear dimension (0.88, 0.51). The total scores for mental health among the participants during the control period were lower than those during the outbreak period (difference = −0.22; 95% CI = −0.25, −0.18). Lower scores were also seen during the control period, compared to those in the outbreak period, for depression (difference = −0.18; 95% CI = −0.23, −0.13), neurasthenia (difference = −0.31; 95% CI = −0.36, −0.25), fear (difference = −0.37; 95% CI = −0.43, −0.31), compulsion anxiety (difference = −0.13; 95% CI = −0.16, −0.09), and hypochondriasis (difference = −0.09; 95% CI = −0.12, −0.06).Conclusions: During the COVID-19 global pandemic, the mental health of women undergoing ART treatment in Xi'an, China, was primarily manifested as fear. As the pandemic was brought under control, the mental health of ART-treated women improved. As evidenced by these results, the COVID-19 pandemic influences the mental health of women undergoing ART treatment, and clinicians should be aware of this for similar future situations.

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and Escherichia coli (E. coli) are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Co-infection with H9N2 AIV and E. coli significantly increased the mortality rate of mice compared to single viral or bacterial infections. It also led to the development of more severe lung lesions compared to single viral or bacterial infections. Co-infection further causes a storm of cytokines, which aggravates the host’s disease by dysregulating the JAK/STAT/SOCS and ERK1/2 pathways. Moreover, co-infection mutually benefited the virus and the bacteria by increasing their pathogen loads. Importantly, nitric oxide synthase 2 (NOS2) expression was also significantly enhanced by the co-infection. It played a key role in the rapid proliferation of E. coli in the presence of the co-infecting H9N2 virus. Therefore, our study underscores the role of NOS2 as a determinant for bacteria growth and illustrates its importance as an additional mechanism that enhances influenza virus-bacteria synergy. It further provides a scientific basis for investigating the synergistic infection mechanism between viruses and bacteria.

Filaggrin, encoded by the FLG gene, plays a crucial role in the barrier function of epidermis, but the association between FLG loss-of-function mutations and infectious skin diseases has not been systematically studied. FLG coding sequences from 945 patients with leprosy and 916 healthy controls were captured and enriched using an array-based high-throughput system, and subjected to next-generation sequencing. The loss-of-function mutations found were further validated by Sanger sequencing. A total of 21 loss-of-function mutations were found in 945 patients with leprosy, with a carrier rate of 17.53%, while the prevalence of these mutations in 916 healthy controls was 14.77%, which was significantly lower than in patients. Two individual FLG loss-of-function mutations (K4022X and Q1790X) were found to be significantly associated with leprosy. These results suggest a possible role for filaggrin in defending against leprosy pathogens.

Objective: To demonstrate the association between pre-pregnancy maternal overweight, obesity, and perinatal outcomes of singletons conceived by assisted reproductive technology (ART).Design: Retrospective cohort study from 2006 to 2015 data from a single ART center.Setting: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Northwestern China.Patients: We included 7,818 women undergoing ART and their singleton infants.Interventions: None.Main Outcome Measure: The primary outcome measures were preterm birth (PTB), macrosomia, low birth weight, small for gestational age, and large for gestational age (LGA).Results: We experienced an increase in the risk of PTB, macrosomia, and LGA in overweight and obese groups compared with that in normal-weight groups [PTB: overweight vs. normal weight: odds ratio [OR] = 1.44, 95% CI: 1.18–1.75; obesity vs. normal weight: OR = 1.53, 95% CI: 1.04–2.25; macrosomia: overweight vs. normal weight: OR = 1.78, 95% CI: 1.48–2.14; obesity vs. normal weight: OR = 2.16, 95% CI: 1.52–3.06; LGA: overweight vs. normal weight: OR = 1.63, 95% CI: 1.39–1.90; obesity vs. normal weight: OR = 2.11, 95% CI: 1.57–2.83]. We observed a significant interaction between maternal BMI and fresh/frozen embryo transfer on PTB and LGA (P = 0.030; P = 0.030). Fresh embryo transfer significantly increased the effect of maternal BMI on LGA (fresh: OR = 1.14, 95% CI: 1.10–1.18; frozen: OR = 1.09, 95% CI: 1.04–1.13), and frozen embryo transfer increased the effect of maternal BMI on PTB (fresh: OR = 1.03, 95% CI: 0.99–1.08; frozen: OR = 1.09, 95% CI: 1.04–1.15).Conclusions: Pre-pregnancy maternal overweight and obesity were associated with higher risks of PTB, macrosomia, and LGA in ART-conceived singletons. These associations were affected by the timing of embryo transfer (fresh/frozen embryo transfer). Therefore, we recommend women before ART to maintain a normal BMI for the prevention of adverse perinatal outcomes.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that is influenced by both genetic and environmental factors. However, the etiology of PCOS remains unclear.Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of genetically determined metabolites (GDMs) on the risk of PCOS. We used summary level data of a genome-wide association study (GWAS) on 486 metabolites (n = 7,824) as exposure and a PCOS GWAS consisting of 4,138 cases and 20,129 controls as the outcome. Both datasets were obtained from publicly published databases. For each metabolite, a genetic instrumental variable was generated to assess the relationship between the metabolite and PCOS. For MR analysis, we primarily used the standard inverse variance weighted (IVW) method, while three additional methods—the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods—were performed as sensitivity analyses.Results: Using genetic variants as predictors, we observed a robust relationship between epiandrosterone sulfate (EPIA-S) and PCOS (PIVW = 0.0186, PMR−Egger = 0.0111; PWeighted−median = 0.0154, and PMR−PRESSO = 0.0290). Similarly, 3-dehydrocarnitine, 4-hydroxyhippurate, hexadecanedioate, and β-hydroxyisovalerate may also have causal effects on PCOS development.Conclusions: We identified metabolites that might have causal effects on PCOS development. Our study emphasizes the role of genetic factors underlying the causal relationships between metabolites and PCOS and provides novel insights through the integration of metabolomics and genomics to better understand the mechanisms involved in human disease pathogenesis.

ObjectiveTo investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients.DesignWe conducted a retrospective cohort analysis.SettingThe study was conducted at an IVF clinic in a public hospital.PatientsA total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria.InterventionsNone.Main Outcome MeasureThe primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI).ResultsThe FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose.ConclusionOvarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred.

Objective: To investigate the cumulative live birth rates (CLBR) according to body mass index (BMI) in women undergoing their first in vitro fertilization (IVF).Design: Retrospective cohort analysis.Setting: An IVF clinic in a public hospital.Patients: This is a retrospective study of 14,782 patients undergoing their first fresh IVF cycles and subsequent frozen embryo transfers in our clinic from January 2014 to January 2017. The follow-up for CLBR continued until January 2019. Patients with a BMI 24 kg/m2 were considered to be overweight. Patients with a BMI ≥ 28 kg/m2 were considered to be obese.Intervention(s): None.Primary Outcome Measure: The primary outcome was cumulative live birth rate (CLBR).Result(s): This study illustrated the “inverted U shape” associations between body weight and IVF outcome (CLBR). The turning points in threshold analysis, as found by an automatic search, were BMIs of 18.5 and 30.4 kg/m2. The main finding of this retrospective data analysis is that the CLBR increased in underweight women, plateaued for normal weight and overweight women with a BMI between 18.5 and 30.4 kg/m2, and decreased in obese women.Conclusion(s): The data suggested an “inverted U shape” association between BMI and CLBR. The CLBR increases in underweight women, plateaus in normal weight and overweight women, and then decreases in obese women.

A large number of statistics indicate that broken rock mass always transforms into a flowing channel and leads to water inrush disasters in mining engineering, such as fault, karst, and strongly weathered rock mass. During the process of water inrush, the structure of the broken rock mass is constantly changing due to seepage erosion under high-velocity flow. Therefore, it is of vital importance to quantitatively evaluate the flow behavior of the water inrush related to the seepage erosion in order to prevent or reduce the risks. This study described a coupled nonlinear flow model, which couples the high-velocity seepage, the small particle migration, and the evolution of the broken rock mass structure. The model was verified firstly for simulation of nonlinear flow behavior by comparing with the traditional one. Then, the proposed model was used to simulate the evolution of particle migration and seepage properties of the water inrush through broken rock mass by a numerical case. The simulation results generally agree well with the existing experimental results. The simulations indicate that small particle migration causes the unstable characteristics of the seepage and the heterogeneity properties of the broken rock mass, which lead to the nonlinear flow behavior of the water inrush in both time and space. From a different perspective, it also indicates that the proposed model is capable of simulating the interaction of high-velocity seepage, small particle migration, and evolution of broken rock mass structure in the process of water inrush.

The boundary layer structure is crucial to the formation and intensification of typhoons, but there is still a lack of high-precision turbulence observations in the typhoon boundary layer due to limitations of the observing instruments under typhoon conditions. Using joint observations from multiple ground-based Doppler wind lidars (DWL) collected by the Shanghai Typhoon Institute of China Meteorological Administration (CMA) during the transit of Typhoon Lekima (8–11 August 2019), the characteristics of the wind field and physical quantities (including turbulent kinetic energy (TKE) and typhoon boundary layer height (TBLH)) of the boundary layer of typhoon Lekima were analyzed. The magnitude of TKE was shown to be related not only to the horizontal wind speed but also to the presence of a strong downdraft, which leads to a rapid increase of TKE. The magnitudes of TKE in different quadrants of Typhoon Lekima were also found to differ. The TKE in the front right quadrant of the typhoon was 2.5–6.0 times that in the rear left quadrant and ~1.7 times that in the rear right quadrant. The TKE over the island was larger than that over the urban area. Before Typhoon Lekima made landfall, the TKE increased with decreasing distance to the typhoon center. After typhoon landfall, the TKE changes were different on the left and right sides of the typhoon center, with the TKE on the left decreasing rapidly, while that on the right changed little. The typhoon boundary layer height calculated by five methods was compared and was found to decrease gradually before typhoon landfall and increased gradually afterward. The trends of the TBLH calculated using helicity and TKE were consistent, and both determine the TBLH well, while the maximum tangential wind speed height (humax) was larger than the height calculated by other methods. This study confirms that DWL has a strong detecting capability for the finescale structure of the typhoon boundary layer and provides a powerful tool for the validation of numerical simulations of typhoon structure.

The activation of TGF-β signaling has been implicated in cancer metastasis. Here, the authors show that OTUD1 suppresses metastasis by antagonizing the TGF-β pathway via the deubiquitination of SMAD7, and its loss correlates with poor prognosis in breast cancer.

The secret key rate is one of the main obstacles to the practical application of continuous-variable quantum key distribution (CVQKD). In this paper, we propose a multiplexing scheme to increase the secret key rate of the CVQKD system with orbital angular momentum (OAM). The propagation characteristics of a typical vortex beam, involving the Laguerre–Gaussian (LG) beam, are analyzed in an atmospheric channel for the Kolmogorov turbulence model. Discrete modulation is utilized to extend the maximal transmission distance. We show the effect of the transmittance of the beam over the turbulent channel on the secret key rate and the transmission distance. Numerical simulations indicate that the OAM multiplexing scheme can improve the performance of the CVQKD system and hence has potential use for practical high-rate quantum communications.

Abstract Semiconductor lasers in the deep ultraviolet (UV) range have numerous potential applications ranging from water purification and medical diagnosis to high-density data storage and flexible displays. Nevertheless, very little success was achieved in the realization of electrically driven deep UV semiconductor lasers to date. In this paper, we report the fabrication and characterization of deep UV MgZnO semiconductor lasers. These lasers are operated with continuous current mode at room temperature and the shortest wavelength reaches 284 nm. The wide bandgap MgZnO thin films with various Mg mole fractions were grown on c-sapphire substrate using radio-frequency plasma assisted molecular beam epitaxy. Metal-semiconductor-metal (MSM) random laser devices were fabricated using lithography and metallization processes. Besides the demonstration of scalable emission wavelength, very low threshold current densities of 29~33 A/cm2 are achieved. Numerical modeling reveals that impact ionization process is responsible for the generation of hole carriers in the MgZnO MSM devices. The interaction of electrons and holes leads to radiative excitonic recombination and subsequent coherent random lasing.

Objective: To investigate the characteristics and outcomes of low prognosis patients defined by POSEIDON criteria undergoing IVF treatment.Design: Retrospective cohort analysis.Setting: An IVF clinic in a public hospital.Patients: 18,455 fresh aspirated IVF cycles with subsequently frozen embryo transfer from Jan 2014 to Jan 2017 in a single IVF clinic were included in the analysis. The low prognosis patients were categorized into 4 groups based on POSEIDON criteria: group 1: age < 35, antral follicle count (AFC) ≥ 5, number of oocytes retrieved ≤ 9 in the previous cycle; group 2: age ≥ 35, AFC≥5, number of oocytes retrieved ≤ 9 in the previous cycle; group 3: age < 35, AFC < 5; group 4: age ≥ 35, AFC < 5. The non-low prognosis patients: group 5: AFC ≥ 5, previous number of oocytes retrieved > 9 oocytes; group 6: AFC ≥ 5, no previous ovarian stimulation.Intervention(s): None.Main Outcome Measure: The primary outcome was cumulative live birth rate (CLBR).Result(s): Taking group 1 as reference, the CLBR from young women in group 3 (35.5%, OR 0.9, 95% CI 0.7–1.2) was slightly lower than that in group 1 (44.6%, p = 0.615). The CLBR in group 2 (24.5%, OR 0.6, 95% CI 0.4–0.8, p = 0.004) and group 4 (12.7%, OR 0.4, 95% CI 0.3–0.6, p < 0.001) was significant lower than that in group 1. In non-poor prognosis patients, the CLBR from young women in group 5 (53.5% OR 1.3 95% CI 0.9, 1.7, p = 0.111) was a slight higher than the reference group 1 while the highest CLBR was originated from the first IVF patients with good ovarian reserve in group 6 (66.9%, OR 2.0, 95% CI 1.6, 2.4).Conclusion(s): The CLBRs and implantation rates in the young women (group 3) with diminished ovarian reserve was similar in those young women (group 1), and was significantly higher than in advanced age women with a fair ovarian reserve (group 2). Though patients in group 2 had better ovarian reserve, more oocytes and more embryos, the pregnancy outcome was inferior to that of group 3 patients with poorer ovarian reserve, fewer oocytes and fewer embryos.

Demand-side management is an important method to improve the stability of power consumption and the reliability of power grid. In Energy Internet, the power supplier can obtain more detailed data about users’ behaviour with numerous smart devices and advanced information network. Here, the utility function of power supplier is established by using the utility function of different users at different times, explicitly taking into account the economic operation's impact. The authors propose a Stackelberg game model to formulate the gaming process between users and power supplier. The authors convert the model into a convex problem to maximum power supplier's benefit, and then calculate the corresponding optimal time-of-use prices, and optimal economic operation power. The simulation results show that the model is effective and has a better result than the traditional profit-only model and non-time-of-use electricity pricing model.

Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.

Groundwater is an important factor of slope stability, and 90% of slope failures are related to the influence of groundwater. In the past, free surface calculations and the prediction of water inflow were based on Darcy's law. However, Darcy's law for steady fluid flow is a special case of non-Darcy flow, and many types of non-Darcy flows occur in practical engineering applications. In this paper, based on the experimental results of laboratory water seepage tests, the seepage state of each soil layer in the open-pit slope of the Yanshan Iron Mine, China, were determined, and the seepage parameters were obtained. The seepage behaviour in the silt layer, fine sand layer, silty clay layer and gravelly clay layer followed the traditional Darcy law, while the gravel layers showed clear nonlinear characteristics. The permeability increases exponentially and the non-Darcy coefficient decreases exponentially with an increase in porosity, and the relation among the permeability, the porosity and the non-Darcy coefficient is investigated. A coupled mathematical model is established for two flow fields, on the basis of Darcy flow in the low-permeability layers and Forchheimer flow in the high-permeability layers. In addition, the effect of the seepage in the slope on the transition from Darcy flow to Forchheimer flow was considered. Then, a numerical simulation was conducted by using finite-element software (FELAC 2.2). The results indicate that the free surface calculated by the Darcy–Forchheimer model is in good agreement with the in situ measurements; however, there is an evident deviation of the simulation results from the measured data when the Darcy model is used. Through a parameter sensitivity analysis of the gravel layers, it can be found that the height of the overflow point and the water inflow calculated by the Darcy–Forchheimer model are consistently less than those of the Darcy model, and the discrepancy between these two models increases as the permeability increases. The necessity of adopting the Darcy–Forchheimer model was explained. The Darcy–Forchheimer model would be applicable in slope engineering applications with highly permeable rock.

In this paper, the effect of chloride ions on the development of corrosion pits in different reinforced concrete under different environmental conditions is studied. A fitting model for the size distribution of pits in seawater and sea-sand concrete (SSC) under different curing modes is established, and time-dependent fractal features are examined. Under wet/dry chloride cycles, the weight loss rate and corrosion rate of steel bars are higher, and the number of corrosion pits appears to increase on a small scale within 60-day. A majority of the corrosion is metastable pitting, and we propose a model to describe the size distribution of pitting in different periods. The good agreement between the proposed model and the available data illustrates that the proposed model is reliable and accurate. Macroscopic pitting occurs first in wet/dry chloride cycles. With the increase of concrete age, the size distribution of pits under wet/dry chloride cycles is uneven, and the pit sizes in submerged concrete tend to be equal.