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Abstract This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

Abstract Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

PurposeThe aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR).MethodsThis retrospective cohort study involved 1,172 euthyroid women aged 20–40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study’s subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%).ResultsFor the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007].ConclusionsTAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

A novel regression model, monotonic inner relation-based non-linear partial least squares (MIR-PLS), is proposed to address complex issues like limited observations, multicollinearity, and nonlinearity in Chinese Medicine (CM) dose-effect relationship experimental data. MIR-PLS uses a piecewise mapping function based on monotonic cubic splines to model the non-linear inner relations between input and output score vectors. Additionally, a new weight updating strategy (WUS) is developed by leveraging the properties of monotonic functions. The proposed MIR-PLS method was compared with five well-known PLS variants: standard PLS, quadratic PLS (QPLS), error-based QPLS (EB-QPLS), neural network PLS (NNPLS), and spline PLS (SPL-PLS), using CM dose-effect relationship datasets and near-infrared (NIR) spectroscopy datasets. Experimental results demonstrate that MIR-PLS exhibits general applicability, achieving excellent predictive performances in the presence or absence of significant non-linear relationships. Furthermore, the model is not limited to CM dose-effect relationship research and can be applied to other regression tasks.

Many correlation analysis methods can capture a wide range of functional types of variables. However, the influence of uncertainty and distribution status in data is not considered, which leads to the neglect of the regularity information between variables, so that the correlation of variables that contain functional relationship but subject to specific distributions cannot be well identified. Therefore, a novel correlation analysis framework for detecting associations between variables with randomness (RVCR-CA) is proposed. The new method calculates the normalized RMSE to evaluate the degree of functional relationship between variables, calculates entropy difference to measure the degree of uncertainty in variables and constructs the copula function to evaluate the degree of dependence on random variables with distributions. Then, the weighted sum method is performed to the above three indicators to obtain the final correlation coefficient R. In the study, which considers the degree of functional relationship between variables, the uncertainty in variables and the degree of dependence on the variables containing distributions, cannot only measure the correlation of functional relationship variables with specific distributions, but also can better evaluate the correlation of variables without clear functional relationships. In experiments on the data with functional relationship between variables that contain specific distributions, UCI data and synthetic data, the results show that the proposed method has more comprehensive evaluation ability and better evaluation effect than the traditional method of correlation analysis.

Abstract The aim of the study is to compare the outcomes between the insemination methods of conventional in vitro fertilization and intracytoplasmic sperm injection in infertile women with thyroid autoimmunity and non-male factor infertility. This was a retrospective cohort study which included women with thyroid autoimmunity and non-male factor infertility. Reproductive outcomes such as embryo development parameters and clinical outcomes were compared between the two groups. The propensity score matching was applied to balance the general characteristics with significant differences between the two groups. Generalized estimating equations were used to explore the impact of ICSI on the embryo development potential of the inseminated oocytes. Sensitivity analysis using E-values was used to account for unknown confounders. After 1:2 propensity score matching, the general characteristics were all comparable. The good cleavage embryo rate, blastocyst utilization rate, and good blastocyst rate were significantly lower in the intracytoplasmic sperm injection group than those in the conventional in vitro fertilization group. After controlling for the confounding factors, intracytoplasmic sperm injection was significantly negatively associated with development of usable blastocysts and good blastocysts, while showed no impact on fertilized oocytes, usable cleavage embryos and good cleavage embryos. Although limited by the limited sample size, there were comparable clinical and obstetrical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection groups. Intracytoplasmic sperm injection neither improved the embryo development potential nor increased the clinical pregnancy and live birth rates compared to conventional in vitro fertilization in the studied population. Prospective studies that randomly divide the studied population in two the two groups and compare the reproductive outcomes are warranted.

Abstract Objective To determine the effect of different translocation characteristics on fertilization rate and blastocyst development in chromosomal translocation patients. Methods This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University From January 2017 to December 2022.All couples were diagnosed as reciprocal translocation or Robertsonian translocation by karyotype of peripheral blood lymphocytes test. After adjusting for confounding factors, the effect of chromosomal rearrangement characteristics, such as carrier sex, translocation type, chromosome length and break sites, on fertilization rate and embryo development were analysed separately using multiple linear regression. Results In cases of Robertsonian translocation (RobT), the carrier sex plays an independent role in fertilization rate, and the male carriers was lower than that of female carriers (76.16% vs.86.26%, P = 0.009). In reciprocal translocation (RecT), the carrier sex, chromosome types and break sites had no influence on fertilization rate, blastocyst formation rate (P > 0.05). However, patients with human longer chromosomal (chromosomes 1–5) translocation have a lower available blastocyst formation rate (Group AB vs. Group CD: 41.49%vs.46.01%, P = 0.027). For male carriers, the translocation types was an independent factor affecting the fertilization rate, and the RobT was the negative one (B = − 0.075, P = 0 0.009). In female carriers, we did not observe this difference (P = 0.227). Conclusions In patients with chromosomal translocation, the fertilization rate may be influenced by carrier sex and translocation type, chromosomes 1–5 translocation may adversely affect the formation of available blastocysts. Break sites have no role in fertilization and blastocyst development.

Often characterized as “sentinels of lake aquatic ecosystems”, different life-form aquatic vegetation covering dynamics reflects both short- and long-term climate fluctuations and human activities. Previous assessments often lack comprehensive spatiotemporal coverage of aquatic vegetation dynamics, prompting a deeper understanding of aquatic vegetation variations and underlying drivers of such change. This article first presents a dataset of semi-decadal-scale trends in aquatic vegetation covering of 616 China’s lakes (>10 km2) from 1986 to 2020, after validating a machine learning method of random forest (RF) by field investigations and literature reviews. The total area of aquatic vegetation in lakes nationwide was varied from 10,345.40 km2 to 17,329.31 km2 (a 67.51 % increase) since 1986, with a growth rate of 169.85 km2/yr. As of 2020, the aquatic vegetation is mainly concentrated in Tibetan Plateau Lake Zone (TPL) (55.99 %) and Eastern Plain Lake Zone (EPL) (25.86 %), followed by other regions. It was identified the changes in aquatic vegetation area experienced three periods: moderate growth (1986–1999), slight losses (2000–2010), and marked recovery (2011–2020). Specifically, the TPL experienced the most remarkable expansion, primarily contrbution from submerged aquatic vegetation (SAV). It is found that smaller lakes in plain area are more conducive to the growth of aquatic vegetation, as shown by the increase in the percentage of aquatic vegetation area (PAV) with the decrease in lake size. But the lakes in TPL showed after 2010 larger lakes are more advantageous in aquatic vegetation recovery, attributing to climate-induced lake expansion. Furthermore, lakes with more intricately shapes also exhibited relative advantages in aquatic vegetation expansion. Geographic and climatic factors also played a pivotal role, with altitude notably influencing temperature and precipitation, thus exerting a considerable impact on aquatic vegetation growth. This study have estimated the semi-decade dynamic characteristics of aquatic vegetation in lakes across China since 1986, concluded that aquatic vegetation ushered in a vigorous recovery period around 2010, offering compelling evidence for the increasing greening trend of aquatic ecosystems.

Abstract Background Previous studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased. However, for patients with diminished ovarian reserve (DOR) after ovarian surgery, how to choose the most appropriate controlled ovarian hyperstimulation protocol has not been concluded. Compared with the traditional agonist regimen, the gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols are simple to operate and have a shorter cycle, which are often used in patients with DOR. So the purpose of our study is to compare the assisted reproductive outcomes of these three controlled ovarian hyperstimulation protocols in patients with DOR following laparoscopic cystectomy of ovarial endometrioma. Methods In this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 to 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate. Results No significant differences in the age of the female patients and their spouses and female patients’ body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P > 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P 0.05). Conclusion In conclusion, for patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, GnRH antagonist protocol and PPOS protocol can obtain better ovulation induction outcomes and cumulative live birth rate than microstimulation protocol, and are more suitable ovulation induction protocols.

Particle swarm optimization (PSO) has been successfully applied to various complex optimization problems due to its simplicity and efficiency. However, the update strategy of the standard PSO algorithm is to learn from the global best particle, making it difficult to maintain diversity in the population and prone to premature convergence due to being trapped in local optima. Chaos search mechanism is an optimization technique based on chaotic dynamics, which utilizes the randomness and nonlinearity of a chaotic system for global search and can escape from local optima. To overcome the limitations of PSO, an improved particle swarm optimization combined with double-chaos search (DCS-PSO) is proposed in this paper. In DCS-PSO, we first introduce double-chaos search mechanism to narrow the search space, which enables PSO to focus on the neighborhood of the optimal solution and reduces the probability that the swarm gets trapped into a local optimum. Second, to enhance the population diversity, the logistic map is employed to perform a global search in the narrowed search space and the best solution found by both the logistic and population search guides the population to converge. Experimental results show that DCS-PSO can effectively narrow the search space and has better convergence accuracy and speed in most cases.

The aim of this study was to obtain polysaccharides from Hovenia dulcis fruit pedicels, and further evaluate its ability to scavenge free radicals and inhibit the oxidation of biological macromolecules (proteins, lipids, DNA). On the basis of a single-factor experiment, the hot water extraction process of polysaccharides from Hovenia dulcis fruit pedicels was optimized using orthogonal test combined with an analysis of variance. The ability of the extracted polysaccharides to scavenge DPPH and ABTS+ free radicals was determined. In addition, Cu2+/H2O2, FeSO4 and APPH were used to induce the oxidation of bovine serum albumin, linoleic acid and herring sperm DNA, respectively, to construct in vitro protein, lipid and DNA oxidation models and the ability of the extracted polysaccharides to inhibit biological macromolecule oxidation in vitro was evaluated. The results showed that the volume fraction of ethanol precipitation had a significant effect on the yield of polysaccharides from Hovenia dulcis fruit pedicels (P

Abstract Background This study aimed to explore the factors that affect insured’s perceptions of convenience of the basic medical insurance (PCBMI) in Harbin, China and to diagnose the key problems to further propose corresponding measures. The findings provide evidence-based support for the reform of convenience of the basic medical insurance system (BMIS) and the cultivation of public literacy. Methods We adopted a mixed methods design composing a multivariate regression model using the data from a cross-sectional questionnaire survey (n = 1045) of residents who were enrolled for BMIS in Harbin to identify the factors influencing the PCBMI. A quota sampling method was further adopted. Semi-structured interviews were then conducted with 30 important information providers selected by convenience sampling. Interpretative phenomenological analysis was employed to summarize and analyze the key problems. Results Overall, approximately 51% of respondents reported poor PCBMI. The logistic regression model showed that insured without outpatient experience within two weeks (OR = 2.522, 95% CI = 1.267–5.024), had poorer levels of understanding of basic medical insurance information (OR = 2.336, 95% CI = 1.612–3.386), lived in rural areas (OR = 1.819, 95% CI = 1.036–3.195), had low levels of annual out-of-pocket medical expenses (OR = 1.488, 95% CI = 1.129–1.961), and were more likely to give the PCBMI a worse evaluation than their counterparts. The results of the qualitative analysis showed that the key problem areas of the PCBMI were the design of the BMIS, the cognitive biases of the insured, publicity information about the BMIS, and the health system environment. Conclusions This study found that in addition to the design of BMIS, the cognition of the insured, the BMIS information publicity and the health system environment are also the key problems hindering PCBMI. While optimizing system design and implementation, Chinese policymakers need to focus on the insured with low PCBMI characteristics. Moreover, it is necessary to focus on exploring effective BMIS information publicity methods, supporting public policy literacy and improving the health system environment.

Abstract To investigate whether there is a relationship between TSH levels on the 14th day post embryo transfer (D14 TSH levels) and the reproductive outcomes in euthyroid women who are free from levothyroxine (LT4) treatment and undergo the first in vitro fertilization /intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET) cycles with the homogeneous ovarian stimulation protocols. This was a prospective study including a total of 599 euthyroid women undergoing the first IVF/ICSI ET cycles. Serum samples were collected and frozen on the 14th day post embryo transfer. TSH levels were measured after the confirmation of clinical pregnancy. The patients were divided into three groups (low-normal ≤ 2.5 mIU/L; high-normal 2.5–4.2 mIU/L; and high > 4.2 mIU/L) based on D14 TSH levels. Reproductive outcomes were compared among the three groups. Binary logistic regression analyses and generalized additive mixed models with smoothing splines were used to investigate the relationship between TSH levels and reproductive outcomes. D14 TSH levels were significantly elevated compared to basal TSH levels, and the degree of TSH elevation was significantly higher in pregnant women compared to that in non-pregnant women. The clinical pregnancy and live birth rates increased significantly in the high-normal D14 TSH groups, and doubled in the high D14 TSH groups compared to the low TSH groups. When adjusted by age, basal TSH, AMH, E2, endometrial thickness, type and causes of infertility, and transferred embryos, the dose-dependent relationships between D14 TSH and clinical pregnancy and live birth were observed. Obstetric outcomes in singleton or twins live birth among the different D14 TSH groups were similar. Elevated D14 TSH levels were associated with better clinical pregnancy and live birth rates, and were not associated with worse obstetric outcomes. The mechanisms to explain the phenomenon remained to be studied.

Abstract Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.

Neighborhood rough set is considered an essential approach for dealing with incomplete data and inexact knowledge representation, and it has been widely applied in feature selection. The Gini index is an indicator used to evaluate the impurity of a dataset and is also commonly employed to measure the importance of features in feature selection. This article proposes a novel feature selection methodology based on these two concepts. In this methodology, we present the neighborhood Gini index and the neighborhood class Gini index and then extensively discuss their properties and relationships with attributes. Subsequently, two forward greedy feature selection algorithms are developed using these two metrics as a foundation. Finally, to comprehensively evaluate the performance of the algorithm proposed in this article, comparative experiments were conducted on 16 UCI datasets from various domains, including industry, food, medicine, and pharmacology, against four classical neighborhood rough set-based feature selection algorithms. The experimental results indicate that the proposed algorithm improves the average classification accuracy on the 16 datasets by over 6%, with improvements exceeding 10% in five. Furthermore, statistical tests reveal no significant differences between the proposed algorithm and the four classical neighborhood rough set-based feature selection algorithms. However, the proposed algorithm demonstrates high stability, eliminating most redundant or irrelevant features effectively while enhancing classification accuracy. In summary, the algorithm proposed in this article outperforms classical neighborhood rough set-based feature selection algorithms.

Summary: Here, we present a protocol for exploring the effects of PPP1R15A inhibitor, Sephin1, on antitumor immunity of B16F1 subcutaneous tumor in mice. We describe steps for constructing single-cell transcriptome and TCR libraries, sequencing, and using sequencing data for the integration of expression and TCR data. We then detail procedures for gene differentiation, regulon and cell-cell communication analysis, and validation of single-cell analysis results.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Alkene epoxidation, whose products are important intermediates for the manufacture of pharmaceuticals and epoxy resins, has attracted extensive attention. Unlike the conventional electrochemical Br−/Br2-mediated epoxidation, here the authors report a photoelectrochemical Br−/BrO−- mediated system to achieve efficient epoxidation performance on α-Fe2O3.

Abstract To model and evaluate the reliability of wind turbine (WT) under imperfect repair, an improved Log-linear Proportional Intensity Model (LPIM)-based method was proposed. Initially, using the three-parameter bounded intensity process (3-BIP) as the benchmark failure intensity function of LPIM, an imperfect repair effect-aware WT reliability description model was developed. Among them, the 3-BIP was used to describe the evolution process of the failure intensity in the stable operation stage with running time, while the LPIM reflected the repair effect. Second, the estimation problem for model parameters was transformed into a minimum solution problem for a nonlinear objective function, which was then solved using the Particle Swarm Optimization algorithm. The confidence interval of model parameters was finally estimated using the inverse Fisher information matrix method. Key reliability indices interval estimation based on the Delta method and point estimation was derived. The proposed method was applied to a wind farm’s WT failure truncation time. The proposed method has a higher goodness of fit based on verification and comparison. As a result, it can bring the evaluated reliability closer to engineering practice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites—C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)—involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Objective: To assess the association between dietary patterns and glycemic control among patients with type II diabetes mellitus (T2DM). Design: A cross-sectional study. Site: The 2015–2018 National Health and Nutrition Examination Survey (NHANES). Participants: A total of 1646 T2DM patients were included, of whom 854 were hyperglycemia. Methods: Main dietary patterns were identified using the sparse principal components analysis (SPCA). Logistic regression analysis was applied to investigate the association between each dietary pattern and the risk of hyperglycemia with odds ratios (OR) and 95% confidence intervals (CI). SPCA analysis yielded five significant principal components (PC), which represented five main dietary patterns. Results: PC1, characterized by a high intake of sweets, red meat and processed meat, was associated with higher odds of hyperglycemia in patients who underwent hyperglycemic drug or insulin treatments (OR: 1.71, 95% CI: 1.10–2.64). PC5, characterized by high in red meat, while low in coffee, sweets, and high-fat dairy consumption. The relationship between the PC5 and hyperglycemia was marginal significance (OR: 0.63, 95% CI: 0.38–1.02). PC2 was characterized by a high consumption of green vegetables, other vegetables, and whole grains, and low intake of potatoes and processed meat. In patients with the hyperglycemic drug and insulin free, higher PC2 levels were related to lower odds of hyperglycemia (OR: 0.45, 95% CI: 0.21–0.96). Conclusions: High intake of sweets, red meat, and processed meat might be detrimental to glycemic control in patients with drug-treated T2DM. High in red meat, while low in coffee, sweets, and high-fat dairy consumption may be beneficial to glycemic control. In addition, high consumption of green vegetables, other vegetables, and whole grains, and low intake of potatoes and processed meat may be good for glycemic control in patients without drug-treated T2DM. Resumen: Objetivo: Evaluar la relación entre el patrón dietético y el control de la glucosa en sangre en los pacientes con diabetes mellitus tipo II (DM2). Diseño: Estudio transversal. Sitio: Encuesta Nacional de Salud y Nutrición 2015-2018 (NHANES). Participantes: Un total de 1.646 pacientes con DM2 fueron incluidos, de los cuales 854 fueron pacientes con hiperglucemia. Método: Se utilizó el método de análisis de componentes principales escasos (SPCA) para determinar el modo dietético principal. Se aplicó un análisis de regresión logística para estudiar la relación entre cada patrón dietético y el riesgo de hiperglucemia con una relación de relación (OR) y un intervalo de confianza (IC) del 95%. El análisis del SPCA ha obtenido 5 componentes principales importantes (PC), que representan los 5 principales patrones alimenticios. Resultados: El PC1 se caracteriza por una alta ingesta de dulces, carnes rojas y procesadas, y se asocia con una mayor probabilidad de hiperglucemia en los pacientes tratados con medicamentos hiperglucémicos o insulina (OR: 171; IC 95%: 1,10-2,64). El PC5, que se caracteriza por un alto contenido de carne roja, mientras que el consumo de café, dulces y productos lácteos ricos en grasas es bajo. La relación entre PC5 y la hiperglucemia fue marginal (OR: 0,63; IC 95%: 0,38-1,02). El PC2 se caracteriza por un alto consumo de verduras verdes, otras verduras y cereales integrales, y una baja ingesta de patatas y carne procesada. Los niveles más altos de PC2 se asociaron con una menor probabilidad de hiperglucemia (OR: 4,45; IC 95%: 0,21-0,96) en los pacientes que tomaban medicamentos hiperglucémicos y no tenían insulina. Conclusión: La alta ingesta de dulces, carnes rojas y procesadas puede no ser propicia para el control de la glucosa en sangre en los pacientes con DM2 tratados con medicamentos. La ingesta de carne roja alta, café bajo, dulces y productos lácteos ricos en grasas puede favorecer el control de la glucosa en sangre. Además, el alto consumo de verduras verdes, otras verduras y cereales integrales, la baja ingesta de patatas y de carne procesada pueden favorecer el control de la glucosa en sangre en los pacientes con DM2 sin tratamiento farmacológico.

In order to improve the energy efficiency of the internal combustion engine and replace fossil fuel with alternative fuels, a concept of the methanol-syngas engine was proposed and the prototype was developed. Gasoline and dissociated methanol gas (GDM) were used as dual fuels and the engine performance was investigated by simulation and experiments. Dissociated methanol gas is produced by recycling the exhaust heat. The performance and combustion process was studied and compared with the gasoline engine counterpart. There is 1.9% energy efficiency improvement and 5.5% fuel consumption reduction under 2000r/min, 100 N ⋅ m working condition with methanol substitution ratio of 10%. In addition, the engine efficiency further improves with an increase of dissociated methanol gas substitution ratio because of the increased heating value of the fuel and effects of hydrogen. The peak pressure in the cylinder and the peak heat release rate of the GDM engine are higher than that of the original gasoline engine, with a phase closer to the top dead center (TDC). Therefore, blending hydrogen-rich gas in the spark-ignition engine can recycle the exhaust heat and improve the thermal efficiency of the engine.

X chromosome dosage compensation (XDC) refers to the process by which X-linked genes acquire expression equivalence between two sexes. Ohno proposed that XDC is achieved by two-fold upregulations of X-linked genes in both sexes and by silencing one X chromosome (X chromosome inactivation, XCI) in females. However, genes subject to two-fold upregulations as well as the underlying mechanism remain unclear. It’s reported that gene dosage changes may only affect X-linked dosage-sensitive genes, such as protein complex coding genes (PCGs). Our results showed that in human PCGs are more likely to escape XCI and escaping PCGs (EsP) show two-fold higher expression than inactivated PCGs (InP) or other X-linked genes at RNA and protein levels in both sexes, which suggest that EsP may achieve upregulations and XDC. The higher expressions of EsP possibly result from the upregulations of the single active X chromosome (Xa), rather than escaping expressions from the inactive X chromosome (Xi). EsP genes have relatively high expression levels in humans and lower dN/dS ratios, suggesting that they are likely under stronger selection pressure over evolutionary time. Our study also suggests that SP1 transcription factor is significantly enriched in EsP and may be involved in the up-regulations of EsP on the active X. Finally, human EsP genes in this study are enriched in the toll-like receptor pathway, NF-kB pathway, apoptotic pathway, and abnormal mental, developmental and reproductive phenotypes. These findings suggest misregulations of EsP may be involved in autoimmune, reproductive, and neurological diseases, providing insight for the diagnosis and treatment of these diseases.

Plain Language Summary To investigate the association between β-hCG and reproductive and obstetrical outcomes in women with cleavage ET and to establish different β-hCG cutoff values for the prediction of reproductive outcomes, this study retrospectively included 6909 infertile women who were divided into different groups based on the number and quality of transferred embryos, age, and transfer protocols. The cutoff values of β-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates decreased significantly in the higher β-hCG groups. In conclusion, the interpretation of β-hCG levels must consider the number and quality of embryos and transfer protocols. When β-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes.

BackgroundThe perceptions of the benefits of the basic medical insurance system among the insured not only reflect the system's performance but also the public's basic medical insurance policy literacy, valuable information for countries that have entered the stage of deepening reform. This study aims to examine the factors that affect the perceptions of the benefits of the basic medical insurance system in China, diagnose the key problems, and propose corresponding measures for improvement.MethodsA mixed method design was used. Data for the quantitative study were obtained from a cross-sectional questionnaire survey (n = 1,045) of residents of Harbin who had enrolled for basic medical insurance system. A quota sampling method was further adopted. A multivariate logistic regression model was then employed to identify the factors influencing the perceptions of the benefits of the basic medical insurance system, followed by semi-structured interviews with 30 conveniently selected key informants. Interpretative phenomenological analysis was used to analyze the interview data.ResultsApproximately 44% of insured persons reported low perceptions of benefits. The logistic regression model showed that low perceptions of the benefits of the basic medical insurance system was positively correlated with the experience of daily drug purchases (OR = 1.967), perceptions of recognition with basic medical insurance system (OR = 1.948), perceptions of the financial burden of participation costs (OR = 1.887), perceptions of the convenience of using basic medical insurance for medical treatment (OR = 1.770), perceptions of the financial burden of daily drug purchases costs (OR = 1.721), perceptions of the financial burden of hospitalization costs (OR = 1.570), and type of basic medical insurance system (OR = 1.456). The results of the qualitative analysis showed that the key problem areas of perceptions of the benefits of the basic medical insurance system were: (I) system design of basic medical insurance; (II) intuitive cognition of the insured; (III) rational cognition of the insured; and (IV) the system environment.ConclusionsImproving the perceptions of the benefits of the basic medical insurance system of the insured requires joint efforts in improving system design and implementation, exploring effective publicity methods of basic medical insurance system information, supporting public policy literacy, and promoting the health system environment.

ObjectiveTo explore the cumulative outcomes and influencing factors of patients with discrepancies between age and Anti-Müllerian hormone (AMH) levels in the early follicular phase prolonged protocol.MethodsA total of 1282 cycles of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) assisted pregnancy with the early follicular phase prolonged protocol in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from September 2015 to December 2020 were retrospectively analyzed. They were divided into the young low-AMH group (n=1076) and the older high-AMH group (n=206). The primary outcomes included cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). Secondary outcomes included the number of oocytes retrieved, number of available embryos, clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate (MR), pregnancy complications, and neonatal outcomes.ResultsThe CPR (68.7% vs. 59.4%) and the LBR (60.7% vs. 43.1%) in the young low-AMH group were higher than those in the older high-AMH group. In contrast, the number of oocytes retrieved (11 vs. 17), number of available embryos (5 vs. 8), and MR (10.6% vs. 18.3%) in the young low-AMH group were lower. There was no significant difference between the two groups in the CCPR, CLBR, pregnancy complications, and neonatal outcomes. Logistic regression analysis showed that infertility duration, basal follicle-stimulating hormone (FSH), and antral follicle count (AFC) correlated with CCPR, while maternal age, type of infertility, basal FSH, AFC, and infertility duration correlated with CLBR. The area under the receiver operating characteristic curves (ROC) curve for the combined model of infertility duration, AFC, and basal FSH to predict cumulative pregnancy was 0.629 (95%CI:0.592-0.666), while the combined model of maternal age, AFC, basal FSH, infertility duration, and type of infertility to predict cumulative live birth was 0.649 (95%CI:0.615-0.682).ConclusionAlthough AMH levels are low by contrast, young patients have a favorable outcome after IVF/ICSI. In patients with discrepancies between age and AMH levels in the early follicular phase prolonged protocol, maternal age correlates better with cumulative live birth. The model that combines maternal age and other factors can help predict cumulative live birth, but its value is limited.

Summary: Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) is an important factor in the integrated stress response (ISR) in mammals and may play a crucial role in tumorigenesis. In our studies, we found an inhibitor of PPP1R15A, Sephin1, plays a protumorigenic role in mouse tumor models. By analyzing the single-cell transcriptome data of the mouse tumor models, we found that in C57BL/6 mice, Sephin1 treatment could lead to higher levels of ISR activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. In addition, T cell receptor (TCR) repertoire analysis demonstrated that the clonal expansion of tumor-specific T cells was inhibited by Sephin1. A special TCR + macrophage subtype in tumor was identified to be significantly depleted upon Sephin1 treatment, implying its key antitumor role. These results suggest that PPP1R15A has the potential to be an effective target for tumor therapy.

Abstract Colorectal cancer (CRC) is considered to be a leading cause of cancer-related death. Centromere protein O (CENPO) can prevent the separation of sister chromatids and cell death after spindle injury. Nevertheless, the role of CENPO in CRC has not been reported. The expression level of CENPO in CRC was revealed by TCGA database and immunohistochemical (IHC) staining. Subsequently, the loss-of-function assays were performed to identified the role of CENPO in CRC in vitro and in vivo. Our data demonstrated that CENPO was highly expressed in CRC. The expression of CENPO was positively correlated with the deterioration of CRC. Moreover, CENPO knockdown inhibited the malignant phenotypes of CRC cells, which was characterized by slowed proliferation, cycle repression at G2, promotion of apoptosis, reduced migration and weakened tumorigenesis. Furthermore, CENPO knockdown downregulated the expression of N-cadherin, Vimentin, Snail, CCND1, PIK3CA and inhibited AKT phosphorylation in CRC cells. Moreover, the function of CENPO in regulating proliferation and apoptosis depended on p53. In summary, CENPO may play a promoting role in CRC through the epithelial mesenchymal transition (EMT) and PI3K/AKT signaling pathway, which can be regarded as a molecular therapeutic target for CRC.

Acetyl tributyl citrate (ATBC) is a widely used phthalate substitute. Although ATBC is considered to be with a safe dosage of up to 1000 mg/kg/day, studies on its effects in some sensitive populations, such as diabetic patients, are relatively rare. Epidemiological studies have shown that there is a link between diabetes and nervous system diseases. However, toxicological studies have not fully confirmed this yet. In this study, glycolipid metabolism, cognitive deficits, brain tissue damage, levels of neurotransmitters, beta-amyloid plaques (Aβ), hyperphosphorylated tau protein (p-Tau), oxidative stress and inflammation, as well as glial cell homeostatic levels in the brain tissue of type 2 diabetes (T2DM) mice, were determined after ATBC exposure (0, 2, 20, and 200 mg/kg/day) for 90 days. The results confirmed that ATBC exposure aggravated the disorder of glycolipid metabolism and caused cognitive deficits in T2DM mice; induced histopathological alterations and Aβ and p-Tau accumulation, and reduced the levels of 5-hydroxytryptamine and acetylcholine in T2DM mouse brains; oxidative stress and glial cell homeostatic levels in T2DM mouse brains were also changed. Some of the adverse effects were gender-dependent. These findings support the theory that T2DM mice, especially males, are more sensitive to ATBC exposure. Although the safe dose of ATBC is high, prolonged exposure at seemingly safe concentrations has the potential to aggravate diabetes symptoms and cause brain tissue damage in T2DM mice.

ObjectiveThis study aimed to determine whether controlled ovarian hyperstimulation (COH) parameters influence the incidence of de novo chromosomal abnormalities (> 4 Mb) in blastocysts and, thus, clinical pregnancy outcomes in preimplantation genetic testing (PGT).MethodsCouples who underwent preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) and monogenic disorders (PGT-M) were included in this study. The relationships of maternal age, paternal age, stimulation protocol, exogenous gonadotropin dosage, duration of stimulation, number of oocytes retrieved and estradiol (E2) levels on human chorionic gonadotropin (hCG) trigger day with the incidence of de novo chromosomal abnormalities were assessed. Blastocysts were biopsied, and nuclear DNA was sequenced using next-generation sequencing (NGS). Clinical pregnancy outcomes after single euploid blastocyst transfers under different COH parameters were assessed. ResultsA total of 1,710 and 190 blastocysts were biopsied for PGT-SR and PGT-M, respectively. The rate of de novo chromosomal abnormalities was found to increase with maternal age (p< 0.001) and paternal age (p = 0.019) in the PGT-SR group. No significant differences in the incidence of de novo chromosomal abnormalities were seen for different maternal or paternal age groups between the PGT-SR and PGT-M groups (p > 0.05). Stratification analysis by gonadotropin dosage, stimulation protocol, duration of stimulation, number of retrieved oocytes and E2 levels on hCG trigger day revealed that de novo chromosomal abnormalities and clinical pregnancy outcomes were not correlated with COH parameters after adjusting for various confounding factors.ConclusionThe rate of de novo chromosomal abnormalities was found to increase with maternal or paternal age. COH parameters were found to not influence the incidence of de novo chromosomal abnormalities or clinical pregnancy outcomes.

Abstract A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to tackle the COVID-19 global pandemic. Here, we describe the development of chimpanzee adenovirus serotypes 6 and 68 (AdC6 and AdC68) vector-based vaccine candidates expressing the full-length transmembrane spike glycoprotein. We assessed the vaccine immunogenicity, protective efficacy, and immune cell profiles using single-cell RNA sequencing in mice. Mice were vaccinated via the intramuscular route with the two vaccine candidates using prime-only regimens or heterologous prime-boost regimens. Both chimpanzee adenovirus-based vaccines elicited strong and long-term antibody and T cell responses, balanced Th1/Th2 cell responses, robust germinal center responses, and provided effective protection against SARS-CoV-2 infection in mouse lungs. Strikingly, we found that heterologous prime-boost immunization induced higher titers of protective antibodies, and more spike-specific memory CD8+ T cells in mice. Potent neutralizing antibodies produced against the highly transmissible SARS-CoV-2 variants B.1.1.7 lineage (also known as N501Y.V1) and B.1.351 lineage (also known as N501Y.V2) were detectable in mouse sera over 6 months after prime immunization. Our results demonstrate that the heterologous prime-boost strategy with chimpanzee adenovirus-based vaccines is promising for further development to prevent SARS-CoV-2 infection.

Abstract Background To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment. Methods This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher’s exact test was used to compare categorical data where appropriate. Results A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P

Guo, Zhang, Guo et al. investigate microbiome alterations in different molecular subtypes of PDAC and report that distinct signatures exist in basal-like tumours, characterized by an increase in certain bacteria, such as Acinetobacter, Pseudomonas and Sphingopyxis. The authors associate increases in these bacteria with increased inflammation and carcinogenic potential, as suggested by pathway analyses.

ObjectivesTo investigate the predictive roles of pre-operative left ventricular (LV) size and ejection fraction (EF) in EF improvement and outcome following revascularization in patients with coronary artery disease (CAD) and LV dysfunction.BackgroundRevascularization may improve EF and long-term outcomes of patients with LV dysfunction. However, the determinants of EF improvement have not yet been investigated comprehensively.Materials and methodsPatients with EF measurements before and 3 months after revascularization were enrolled in a cohort study (No. ChiCTR2100044378). All patients had baseline EF ≤ 40%. EF improvement was defined as absolute increase in EF > 5%. According to LV end-systolic diameter (LVESD) (severely enlarged or not) and EF (≤35% or of 36–40%) at baseline, patients were categorized into four groups.ResultsA total of 939 patients were identified. A total of 549 (58.5%) had EF improved. Both LVESD [odds ratio (OR) per 1 mm decrease, 1.05; 95% CI, 1.04–1.07; P < 0.001] and EF (OR per 1% decrease, 1.06; 95% CI, 1.03–1.10; P < 0.001) at baseline were predictive of EF improvement after revascularization. Patients with LVESD not severely enlarged and EF ≤ 35% had higher odds of being in the EF improved group in comparison with other three groups both in unadjusted and adjusted analysis (all P < 0.001). The median follow-up time was 3.5 years. Patients with LVESD not severely enlarged and EF ≤ 35% had significantly lower risk of all-cause death in comparison with patients with LVESD severely enlarged and EF ≤ 35% [hazard ratio (HR), 2.73; 95% CI, 1.28–5.82; P = 0.009], and tended to have lower risk in comparison with patients with LVESD severely enlarged and EF of 36–40% (HR, 2.00; 95% CI, 0.93–4.27; P = 0.074).ConclusionAmong CAD patients with reduced EF (≤ 40%) who underwent revascularization, smaller pre-operative LVESD and lower EF had greatest potential to have EF improvement and better outcome. Our findings imply the indication for revascularization in patients with LV dysfunction who presented with lower EF but smaller LV size.

Allergic asthma is the most common pulmonary inflammatory disease, and epidemiological studies have revealed that PM2.5 or ambient ozone (O3) exposure contribute to the higher prevalence of allergic asthma. Current experimental evidence focus principally on the pathogenic effect of exposure to a single air pollutant, ignoring the possible synergistic effect of combined exposure to a mix of these pollutants, which is a more realistic scenario. In this study, allergic mice and a nociceptor antagonist were used to explore the mechanisms of co-exposure to these two important air pollutants. Compared with exposure to either PM2.5 or O3, combined exposure to both greatly aggravated allergic asthma in a dose dependent manner, including increased airway hyperresponsiveness, goblet cell metaplasia, more severe airway inflammation and higher oxidative stress levels. In addition, co-exposure in the allergic mice resulted in elevation of the expression of transient receptor potential vanilloid 1 (TRPV1), and of the production of substance P (SP), which exacerbated lung inflammation by neurogenic inflammation. TRPV1 antagonist (capsazepine, CPZ) treatment for the co-exposed allergic mice, markedly attenuated TRPV1 expression and SP release, and reduced airway inflammation and oxidative damage, further alleviating airway hyperresponsiveness. We conclude that neuro-immune interactions might be involved in PM2.5 and O3 co-exposure aggravated allergic asthma.

Diabetic retinopathy (DR) is a common complication and the leading cause of blindness in patients with type 2 diabetes. DR has been shown to be closely correlated with blood glucose levels and the duration of diabetes. However, the onset and progression of DR also display clinical heterogeneity. We applied whole-exome sequencing and RNA-seq approaches to study the gene mutation and transcription profiles in three groups of diabetic patients with extreme clinical phenotypes in DR onset, timing, and disease progression, aiming to identify genetic variants that may play roles in the pathogenesis of DR. We identified 23 putatively pathogenic genes, and ingenuity pathway analysis of these mutated genes reveals their functional association with glucose metabolism, diabetic complications, neural system activity, and dysregulated immune responses. In addition, ten potentially protective genes were also proposed. These findings shed light on the mechanisms underlying the pathogenesis of DR and may provide potential targets for developing new strategies to combat DR.

Abstract At present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

Piezoelectric micromechanical ultrasonic transducers (pMUTs) are new types of distance sensors with great potential for applications in automotive, unmanned aerial vehicle, robotics, and smart homes. However, previously reported pMUTs are limited by a short sensing distance due to lower output sound pressure. In this work, a pMUT with a special dual-ring structure based on scandium-doped aluminum nitride (ScAlN) is proposed. The combination of a dual-ring structure with pinned boundary conditions and a high piezoelectric performance ScAlN film allows the pMUT to achieve a large dynamic displacement of 2.87 μm/V and a high electromechanical coupling coefficient (kt2) of 8.92%. The results of ranging experiments show that a single pMUT achieves a distance sensing of 6 m at a resonant frequency of 91 kHz, the farthest distance sensing registered to date. This pMUT provides surprisingly fertile ground for various distance sensing applications.

Abstract Background Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles. Methods A total of 271 patients aged 20–40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted. Results Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P

Abstract Background The aim of this study was to investigate the impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer. Methods Blood samples were collected on the first visit to our department and 14 days after embryo transfer. Women were divided into three groups based on D14 TSH levels, which were compared to basal TSH levels in groups with different clinical outcomes. TSH levels between pregnant and nonpregnant women were also compared. Results The clinical pregnancy rate in women with lower TSH levels 14 days after transfer was slightly but significantly lower (56%, P = 0.05) compared to those with higher TSH levels. Furthermore, TSH levels were significantly elevated 14 days after transfer compared to basal TSH levels in pregnant women and in women who successfully became pregnant (P

ObjectiveThe aim of this study was to investigate whether blastocyst morphology and developmental rate are associated with euploidy and live birth rates (LBRs) in single euploid frozen–thawed embryo transfer (FET) cycles.DesignRetrospective cohort study.MethodsThis study included 431 preimplantation genetic testing for aneuploidy (PGT-A) cycles followed by 393 FET cycles performed at our center from June 2017 to March 2021. All cycles were analyzed for euploidy based on blastocyst morphology (good, average and poor), developmental stage (day 5 and 6) and maternal age (< 35 and ≥ 35 years old). Multivariate logistic analysis models were used to identify the independent effects of conventional blastocyst morphology, developmental rate and morphological parameters (degree of blastocoele expansion, and grade of inner cell mass and trophectoderm (TE)) on LBRs.ResultsIn the group of women aged < 35 years, compared with poor-quality blastocysts, good-quality blastocysts (62.90% vs. 32.46%; odds ratio (OR) 3.163, 95% confidence interval (CI) 2.247–4.451; P < 0.001) and average-quality blastocysts (46.70% vs. 32.46%; OR 1.665, 95% CI 1.287–2.154; P < 0.001) had significantly higher euploidy rates. Additionally, day 5 blastocysts were associated with higher euploidy rates than day 6 blastocysts (49.28% vs. 35.02%; OR 1.506, 95% CI 1.191–1.903; P= 0.001). In the group of women aged ≥ 35 years, euploidy rates were also associated with blastocyst morphology, with 41.86%, 45.65% and 24.39% of good, average and poor-quality embryos, respectively, exhibiting euploidy. However, no relationship was seen between euploidy and blastocyst developmental rate. Multiple logistic regression analysis show that overall blastocyst morphology of euploid embryos was not associated with LBR, only embryos with A-grade TE had significantly higher LBRs than those with C-grade TE (62.71% vs. 45.40%; OR 2.189, 95% CI 1.166–4.109; P=0.015). Similarly, LBRs were significantly higher when day 5 blastocysts were transferred than when day 6 blastocysts were transferred (57.75% vs. 41.67%; OR 2.132, 95% CI 1.370–3.318; P = 0.001).ConclusionPoor-quality embryos have reduced rates of euploidy. However, blastocyst developmental rate only significantly associates with euploidy rates in women aged younger than 35. Furthermore, only TE grade and blastocyst developmental rate are significantly associated with LBRs following FET cycles.

Background Colletotrichum gloeosporioides, a soil-borne fungal pathogen, causes significant yield losses in many plants, including cultivated strawberry (Fragaria × ananassa, 2n = 8x = 56). Thaumatin-like proteins (TLPs) are a large and complex family of proteins that play a vital role in plant host defense and other physiological processes. Methods To enhance our understanding of the antifungal activity of F. × ananassa TLPs (FaTLP), we investigated the genome-wide identification of FaTLP gene families and their expression patterns in F. × ananassa plants upon pathogen infection. Moreover, we used RNA sequencing (RNA-seq) to detect the differences in the expression patterns of TLP genes between different resistant strawberry cultivars in response to C. gloeosporioides infection. Results In total, 76 TLP genes were identified from the octoploid cultivated strawberry genome with a mean length of 1,439 bp. They were distributed on 24 F. × ananassa chromosomes. The FaTLP family was then divided into ten groups (Group I–X) according to the comparative phylogenetic results. Group VIII contained the highest number of TLP family genes. qRT-PCR analysis results indicated that FaTLP40, FaTLP41, FaTLP43, FaTLP68, and FaTLP75 were upregulated following C. gloeosporioides infection in the resistant octoploid strawberry. Conclusions The data showed some differences in TLP gene expression patterns across different resistant strawberry cultivars, as well as faster TLP defense responses to pathogenic fungi in resistant cultivars. This study will aid in the characterization of TLP gene family members found in octoploid strawberries and their potential biological functions in plants’ defenses against pathogenic fungi.

Abuse of psychostimulants, including amphetamines (AMPHs), is a major public health problem with profound psychiatric, medical, and psychosocial complications. The actions of these drugs at the dopamine transporter (DAT) play a critical role in their therapeutic efficacy as well as their liability for abuse and dependence. To date, however, the mechanisms that mediate these actions are not well-understood, and therapeutic interventions for AMPH abuse have been limited. Drug exposure can induce broad changes in gene expression that can contribute to neuroplasticity and effect long-lasting changes in neuronal function. Identifying genes and gene pathways perturbed by drug exposure is essential to our understanding of the molecular basis of drug addiction. In this study, we used Drosophila as a model to examine AMPH-induced transcriptional changes that are DAT-dependent, as those would be the most relevant to the stimulatory effects of the drug. Using this approach, we found genes involved in the control of mRNA translation to be significantly upregulated in response to AMPH in a DAT-dependent manner. To further prioritize genes for validation, we explored functional convergence between these genes and genes we identified in a genome-wide association study of AMPH sensitivity using the Drosophila Genetic Reference Panel. We validated a number of these genes by showing that they act specifically in dopamine neurons to mediate the behavioral effects of AMPH. Taken together, our data establish Drosophila as a powerful model that enables the integration of behavioral, genomic and transcriptomic data, followed by rapid gene validation, to investigate the molecular underpinnings of psychostimulant action.

With the development of multi-network integration,how to ensure efficient interconnections among multiple independent network domains is becoming a key problem.Traditional interdomain routing protocol fails due to the limitation of domain information privacy,where each autonomous domain doesn’t share any specific intra-domain information.A machine learning-based federated routing mechanism was proposed to overcome the existing shortcomings.Each autonomous domain shares intra-domain information implicitly via neural network models and parameters.It not only breaks data islands problems but also greatly reduces the amount of transmitted data shared between domains,then decreases convergence delay of entire network information.Based on the federated routing mechanism,border routers can formulate global optimal routing strategies according to the status of entire network.

Research Question. What is the incidence of de novo chromosome abnormalities (>4 Mb), and are they related to embryo parameters in preimplantation genetic testing for chromosome structural rearrangement (PGT-SR) cycles and preimplantation genetic testing for aneuploidy (PGT-A) cycles? Design. In total, 456 PGT cycles, including 283 PGT-SR cycles and 173 PGT-A cycles, were assessed through comprehensive chromosome screening (CCS) from January 2017 to June 2020 at the Department of Reproductive Medicine of the Third Affiliated Hospital of Zhengzhou University. Trophectoderm (TE) biopsies were sequenced using next-generation sequencing (NGS). The incidence of de novo chromosome abnormalities was calculated, and the relationships between de novo chromosome abnormality rates and maternal age, number of oocytes retrieved, and parameters of cleavage-stage embryos and blastocyst-stage embryos were investigated. Results. The incidence of de novo chromosome abnormalities was 28.0% (318/1,135) in the PGT-SR cycles and 36.3% (214/590) in the PGT-A cycles, which increased with maternal age in both PGT-SR cycles (P = 0.018) and PGT-A cycles (P

The identification and monitoring of cyanobacterial blooms (CBs) is critical for ensuring water security. However, traditional methods are time-consuming and labor-intensive and are not ideal for large-scale monitoring. In operational monitoring, the existing remote sensing methods are also not ideal due to complex surface features, unstable models, and poor robustness thresholds. Here, a novel algorithm, the pseudo-Forel-Ule index (P-FUI), is developed and validated to identify cyanobacterial blooms based on Terra MODIS, Landsat-8 OLI, Sentinel-2 MSI, and Sentinel-3 OLCI sensors. First, three parameters of P-FUI, that is, brightness Y, saturation s, and hue angle α, were calculated based on remote sensing reflectance. Then, the robustness thresholds of the parameters were determined by statistical analysis for a frequency distribution histogram. We validated the accuracy of our approach using high-spatial-resolution satellite data with the aid of field investigations. Considerable results were obtained by using water color differences directly. The overall classification accuracy is more than 93.76%, and the user’s accuracy and producer’s accuracy are more than 94.60% and 94.00%, respectively, with a kappa coefficient of 0.91. The identified cyanobacterial blooms’ spatial distribution with high, medium, and low intensity produced consistent results compared to those based on satellite data. Impact factors were also discussed, and the algorithm was shown to be tolerant of perturbations by clouds and high turbidity. This new approach enables operational monitoring of cyanobacterial blooms in eutrophic lakes.

ObjectiveTo compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR).Patients and MethodsThis was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates.ResultsIn total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14).ConclusionFor women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.

Background: Several complications can contribute to the risk of shock during the chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedure. However, some patients that develop shock do not exhibit any apparent complications, and few studies to date have discussed the risk of unexplained perioperative shock in patients undergoing CTO PCI. Accordingly, this study was designed with the goal of defining perioperative risk factors linked to the odds of unexplained shock during CTO PCI. Methods: In total, this study analyzed data from 924 patients that underwent CTO PCI without any in-hospital complications from January 2016–August 2021. Cardiologists collected data pertaining to patient clinical characteristics, laboratory findings, angiographic findings, and procedural characteristics. Patients were separated into two groups based upon whether or not they experienced perioperative shock. The relationship between specific variables and perioperative shock incidence was assessed via a multivariable stepwise logistic regression approach. A risk-scoring nomogram was then designed for use as a tool to guide patient risk assessment efforts during PCI procedural planning. Results: Overall, 4.8% of these patients (44/924) experienced unexplained perioperative shock. Independent predictors associated with unexplained shock during CTO PCI included baseline systolic pressure (odds ratio (OR) 0.968, 95% confidence interval (CI): 0.945–0.991), baseline heart rate (OR 1.055, 95% CI: 1.020–1.091), baseline hemoglobin (OR 0.970, 95% CI: 0.947–0.994), procedure duration (OR 1.008, 95% CI: 1.002–1.015), J-CTO score (OR 1.521, 95% CI: 1.021–2.267), and use of a retrograde approach (OR 3.252, 95% CI: 1.426–7.415). The unbiased C-index estimate was 0.859, and this model exhibited excellent calibration. Conclusions: The risk of unexplained shock is an important consideration for clinicians performing the CTO PCI procedure. These analyses revealed unexplained shock risk to be independently related to lower baseline systolic pressure, higher baseline heart rate, lower baseline hemoglobin, more procedure time, higher J-CTO score, and more use of a retrograde approach.

This study revealed the microbial compositions in children with bacterial meningitis who were treated with antibiotics and made a comprehensive comparison between blood and CSF specimens for risk and prognosis assessment. We found that microbiome signatures could distinguish patient subsets and were correlated with the CRP level in blood and granulocyte percentage in CSF.