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This study focuses on the flexible job shop scheduling problem with sequence-dependent setup times (FJSP-SDST), and the goal is minimizing the makespan. To solve FJSP-SDST, first, we develop a constraint programming (CP) model to obtain optimal solutions. Due to the NP-hardness of FJSP-SDST, a CP assisted meta-heuristic algorithm (C-VNS-CP) is designed to make use of the advantages of both CP model and cooperative variable neighborhood search (C-VNS). The C-VNS-CP algorithm consists of two stages. The first stage involves C-VNS, for which eight neighborhood structures are defined. In the second stage, CP is used to further optimize the good solution obtained from C-VNS. In order to prove the efficiency of the C-VNS algorithm, CP model, and C-VNS-CP algorithm, experiments of 20 instances are conducted.

Abstract To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.

Abstract With the rapid development of modern science and technology, navigation technology provides great convenience for people's life, but the problem of inaccurate localization in complex environments has always been a challenge that navigation technology needs to be solved urgently. To address this challenge, this paper proposes an augmented reality navigation method that combines image segmentation and multi-sensor fusion tracking registration. The method optimizes the image processing process through the GA-OTSU-Canny algorithm and combines high-precision multi-sensor information in order to achieve accurate tracking of positioning and guidance in complex environments. Experimental results show that the GA-OTSU-Canny algorithm has a faster image edge segmentation rate, and the fastest start speed is only 1.8 s, and the fastest intersection selection time is 1.2 s. The navigation system combining the image segmentation and sensor tracking and registration techniques has a highly efficient performance in real-world navigation, and its building recognition rates are all above 99%. The augmented reality navigation system not only improves the navigation accuracy in high-rise and urban canyon environments, but also significantly outperforms traditional navigation solutions in terms of navigation startup time and target building recognition accuracy. In summary, this research not only provides a new framework for the theoretical integration of image processing and multi-sensor data, but also brings innovative technical solutions for the development and application of practical navigation systems.

A half-dose influenza vaccine (7.5 μg hemagglutinin per strain) has been used for children under 3 years of age for a long time. However, several studies indicate that a full-dose influenza vaccine (15 μg hemagglutinin per strain) may bring more benefit to this population without increasing the risk of adverse reactions. We conducted a clinical study in children aged 6–35 months in China. Participants were randomized to receive two doses of full-dose quadrivalent influenza vaccine (F-QIV), half-dose quadrivalent vaccine (H-QIV), and two half-dose trivalent vaccines (H-TIV) in a 2:2:1:1 ratio. The safety and tolerability profile of the vaccine was evaluated for 6 months postvaccination. Hemagglutination inhibition (HI) antibody titers were measured for immunogenicity assessment. The primary objective was to assess whether the results of all vaccines met the criteria. A total of 1,980 participants were enrolled in the study. Both H-QIV and F-QIV were well tolerated after vaccination. Although the geometric mean increase (GMI), seroconversion rate (SCR), and seroprotection rate (SPR) for both H-QIV and F-QIV were achieved by the criteria, superior immunogenicity in terms of geometric mean titer (GMT) ratio was observed in F-QIV to H-QIV for A/H3N2 (GMT ratio (95% CI) of 1.37 (1.11 ~ 1.68)) and B/Yamagata (1.21 (1.05 ~ 1.39)). Antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. In conclusion, F-QIV and H-QIV were both safe and immunogenic for children. F-QIV induced a stronger immune response to influenza viruses and may provide more protection and benefit by promoting the use of F-QIV in children aged 6–35 months.

Path planning is an essential research topic in the navigation of mobile robots. Currently, rapidly-exploring random tree star (RRT*) and its variants are known for their probabilistic completeness and asymptotic optimality, making them effective in finding solutions for many path planning problems. However, slow convergence rate of the RRT* limits its practical efficiency. To address this problem, this paper proposed an enhanced RRT* algorithm by refining the extension process of the exploring tree. This enhancement aims to guide the tree approaching to obstacles (GAO) while exploring toward the target point. First, GAO-RRT* employed a dual-weighted sample strategy instead of random sample to guide search direction of the exploring tree. Second, a variable step size extension strategy was adopted to increase the efficiency of node generation, balancing searching time and path safety in regions with different obstacles densities. Third, growth status of new nodes was monitored in real-time, and a reverse growth strategy was proposed to guide the exploring tree to escape local optima. In addition, parent node creation procedure for new nodes was used to produce a better initial path. Finally, the proposed GAO-RRT* was compared with three state of the art algorithms on 16 different instances of four representative environments. Compared to RRT*, Quick-RRT* (Q-RRT*), and Fast-RRT* (F-RRT*), the results showed that (1) the average path cost of initial solutions obtained by GAO-RRT* decreased by 38.32%, 29.69%, and 20.44%, respectively; and (2) the average convergence time of solution obtained by GAO-RRT* to suboptimal (1.05*$ C_{best} $) was reduced by 71.22%, 69.69%, and 58.37%, respectively. Simulation results indicated that GAO-RRT* outperforms the compared algorithms in terms of path cost and convergence speed.

With a decentral and global economy, distributed scheduling problems are getting a lot of attention. This paper addresses a distributed flexible job shop scheduling problem (DFJSP) with minimizing makespan, in which three subproblems, namely operations sequencing, factory selection and machine selection must be determined. To solve the DFJSP, a novel mixed-integer linear programming (MILP) model is first developed, which can solve the small-scaled instances to optimality. Since the NP-hard characteristic of DFJSP, a hybrid algorithm (GA-VNS-CP) of genetic algorithm (GA), variable neighborhood search (VNS) and constraint programming (CP). Specifically, the GA-VNS-CP is divided into two stages. The first stage uses the hybrid meta-heuristic algorithms of GA and VNS (GA-VNS), and the VNS is designed to improve the local search ability of GA. In GA-VNS, the encoding only considers the factory selection and the operations sequencing problems, and the machine selection problem is determined by the decoding rule. Because the solution space may be limited by the decoding rule, the second stage uses the CP to extend the solution and further improve the solution. Numerical experiments based on benchmark instances are conducted to evaluate the effectiveness of the MILP model, VNS, CP and GA-VNS-CP. The experimental results show effectiveness of the MILP model, VNS and CP. Moreover, the GA-VNS-CP algorithm has better performance than traditional algorithms and improves 6 current best solutions for benchmark instances.

The hybrid flow shop scheduling problem (HFSP) is an extension of the classic flow shop scheduling problem and widely exists in real industrial production systems. In real production, sequence-dependent setup times (SDST) are very important and cannot be neglected. Therefore, this study focuses HFSP with SDST (HFSP-SDST) to minimize the makespan. To solve this problem, a mixed-integer linear programming (MILP) model to obtain the optimal solutions for small-scale instances is proposed. Given the NP-hard characteristics of HFSP-SDST, an improved artificial bee colony (IABC) algorithm is developed to efficiently solve large-sized instances. In IABC, permutation encoding is used and a hybrid representation that combines forward decoding and backward decoding methods is designed. To search for the solution space that is not included in the encoding and decoding, a problem-specific local search strategy is developed to enlarge the solution space. Experiments are conducted to evaluate the effectiveness of the MILP model and IABC. The results indicate that the proposed MILP model can find the optimal solutions for small-scale instances. The proposed IABC performs much better than the existing algorithms and improves 61 current best solutions of benchmark instances.

Abstract Background Low levels of Free Triiodothyronine (FT3) are associated with poor survival in chronic kidney disease, and the aim of this study was to further assess the relationship between changes in FT3 levels and renal damage in patients with type 2 diabetes based on glomerular and tubular markers. Methods We retrospectively studied 452 type 2 diabetic patients, measured glomerular damage markers (UACR, eGFR) and tubular damage markers (NAG/Cr,β2-MG), analyzed the relationship between FT3 and renal damage by logistic regression models, and plotted restrictive cubic splines. Results 41.6% of subjects had diabetic kidney disease (DKD), and the prevalence of DKD decreased progressively with increasing FT3 levels in the third quartile. Spearman correlation analysis showed that FT3 was negatively associated with UACR, NAG/Cr and β2-MG, while eGFR was positively associated with FT3. Multifactorial analysis, after adjusting for relevant confounders, revealed that compared with the lowest quartile of FT3, the highest quartile reduced the risk of developing urinary albumin (OR = 0.499,95% CI:0.289–0.856), moderate to severe impairment of glomerular filtration rate (OR = 0.106,95% CI:0.032–0.354), renal tubular marker β2 -MG positive (OR = 0.516,95% CI:0.299 to 0.883) and the risk of DKD occurrence (OR = 0.450,95% CI:0.260 to 0.774). In the sample model, FT3 levels below 4.39 pmol/L were associated with an increased risk of glomerular tubule injury and DKD occurrence. Conclusions FT3 is closely associated with glomerular tubular injury and is a protective factor. As FT3 levels (

Abstract Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI

Research on helicopter dispatching has received considerable attention, particularly in relation to post-disaster rescue operations. The survival chances of individuals trapped in emergency situations decrease as time passes, making timely helicopter dispatch crucial for successful rescue missions. Therefore, this study investigates a collaborative helicopter rescue routing problem with time window and limited survival time constraints, solving it using an improved iterative greedy (IIG) algorithm. In the proposed algorithm, a heuristic initialization strategy is designed to generate an efficient and feasible initial solution. Then, a feasible-first destruction-construction strategy is applied to enhance the algorithm’s exploration ability. Next, a problem-specific local search strategy is developed to improve the algorithm’s local search effectiveness. In addition, the simulated annealing (SA) method is integrated as an acceptance criterion to avoid the algorithm from getting trapped in local optima. Finally, to evaluate the efficacy of the proposed IIG, 56 instances were generated based on Solomon instances and used for simulation tests. A comparative analysis was conducted against six efficient algorithms from the existing studies. The experimental results demonstrate that the proposed algorithm performs well in solving the post-disaster rescue helicopter routing problem.

The vehicle routing problem (VRP) is a highly significant and extensively studied issue in post-disaster rescue. In recent years, there has been widespread utilization of helicopters for post-disaster rescue. However, efficiently dispatching helicopters to reach rescue sites in post-disaster rescue is a challenge. To address this issue, this study models the issue of dispatching helicopters as a specific variant of the VRP with time window (VRPTW). Considering that the VRPTW is an NP-hard problem, the genetic algorithm (GA) as one of the prominent evolutionary algorithms with robust optimization capabilities, is a good candidate to deal with this issue. In this study, an improved GA with a local search strategy and global search strategy is proposed. To begin, a cooperative initialization strategy is proposed to generate an initial population with high quality and diversity. Subsequently, a local search strategy is presented to improve the exploitation ability. Additionally, a global search strategy is embedded to enhance the global search performance. Finally, 56 instances extended from Solomon instances are utilized for conducting simulation tests. The simulation results indicate that the average relative percentage increase (RPI) of the distance travelled by helicopters as obtained by the proposed algorithm is 0.178, 0.027, 0.075 and 0.041 times smaller than the average RPIs obtained by the tabu search algorithm, ant colony optimization algorithm, hybrid GA and simulated annealing algorithm, respectively. Simulation results reveal that the proposed algorithm is more efficient and effective for solving the VRPTW to reduce the driving distance of the helicopters in post-disaster rescue.

Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus (SLE). Nevertheless, whether either leptin or resistin has causal impacts on the risk of SLE is still unknown. In this study, two-sample univariable MR analyses and multivariable MR analysis were performed to explore the causal relationships between adipokines and SLE. Additionally, the potential causal effects of SLE on major adipokines were evaluated using reverse MR analyses. The results of inverse-variance weighted (IVW), weighted median, weighted mode and MR‒Egger methods concordantly supported that major adipokines have no causal effects on the risk of SLE. In the multivariable MR IVW analysis with leptin and resistin as covariates, neither leptin (odds ratio (OR) = 3.093, P = 0.067) nor resistin (OR = 0.477, P = 0.311) was identified as an independent risk factor for SLE, which is in line with the univariable MR results. In conclusion, our analyses revealed no evidence to support that these three major adipokines are risk factors for SLE.

Abstract Aims To investigate the relationships and pathways between workplace bullying, workplace spirituality, and job burnout in Chinese paediatric nurses. Design A cross‐sectional descriptive survey was conducted with paediatric nurses from six tertiary hospitals in Hubei Province, China. Methods The study consisted of 402 paediatric nurses. The data were collected using a sociodemographic data questionnaire, Negative Acts Questionnaire‐Revised, Maslach Burnout Inventory‐General Survey and Workplace Spirituality Scale. The model was tested using path analysis techniques within structural equation modelling. Results Workplace bullying had positive and direct effects on the job burnout of paediatric nurses. Workplace spirituality partially mediated the relationship between workplace bullying and burnout. Patient or Public Contribution Workplace spirituality may reduce the incidence of work bullying and job burnout in paediatric nurses. Nursing managers need to consider and cultivate the workplace spirituality of paediatric nurses, with the aim of creating a healthy working environment and ensuring the stability of the nursing team.

With the rise of the Internet of Things (IoT), maintaining data confidentiality and protecting user privacy have become increasingly challenging. End devices in the IoT are often deployed in unattended environments and connected to open networks, making them vulnerable to physical tampering and other security attacks. Different authentication key agreement (AKA) schemes have been used in practice; several of them do not cover the necessary security features or are incompatible with resource-constrained end devices. Their security proofs have been performed under the Random-Oracle model. We present an AKA protocol for end devices and servers. The proposal leverages the ECC-based key exchange mechanism and one-way hash function-based message authentication method to achieve mutual authentication, user anonymity, and forward security. A formal security proof of the proposed scheme is performed under the standard model and the eCK model with the elliptic curve encryption computational assumptions, and formal verification is performed with ProVerif. According to the performance comparison, it is revealed that the proposed scheme offers user anonymity, perfect forward security, and mutual authentication, and resists typical attacks such as ephemeral secret leakage attacks, impersonation attacks, man-in-the-middle attacks, and key compromise impersonation attacks. Moreover, the proposed scheme has the lowest computational and communication overhead compared to existing schemes.

In recent studies, the tumourigenesis and development of endometrial carcinoma (EC) have been correlated significantly with redox. We aimed to develop and validate a redox-related prognostic model of patients with EC to predict the prognosis and the efficacy of immunotherapy. We downloaded gene expression profiles and clinical information of patients with EC from the Cancer Genome Atlas (TCGA) and the Gene Ontology (GO) dataset. We identified two key differentially expressed redox genes (CYBA and SMPD3) by univariate Cox regression and utilised them to calculate the risk score of all samples. Based on the median of risk scores, we composed low-and high-risk groups and performed correlation analysis with immune cell infiltration and immune checkpoints. Finally, we constructed a nomogram of the prognostic model based on clinical factors and the risk score. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. CYBA and SMPD3 were significantly related to the prognosis of patients with EC and used to construct a risk model. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low-and high-risk groups. The nomogram developed with clinical indicators and the risk scores was effective in predicting the prognosis of patients with EC. In this study, a prognostic model constructed based on two redox-related genes (CYBA and SMPD3) were proved to be independent prognostic factors of EC and associated with tumour immune microenvironment. The redox signature genes have the potential to predict the prognosis and the immunotherapy efficacy of patients with EC.

Objective: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. Method: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. Result: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. Conclusion: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Effective path planning (PP) is the basis of autonomous navigation for mobile robots. Since the PP is an NP-hard problem, intelligent optimization algorithms have become a popular option to solve this problem. As a classic evolutionary algorithm, the artificial bee colony (ABC) algorithm has been applied to solve numerous realistic optimization problems. In this study, we propose an improved artificial bee colony algorithm (IMO-ABC) to deal with the multi-objective PP problem for a mobile robot. Path length and path safety were optimized as two objectives. Considering the complexity of the multi-objective PP problem, a well-environment model and a path encoding method are designed to make solutions feasible. In addition, a hybrid initialization strategy is applied to generate efficient feasible solutions. Subsequently, path-shortening and path-crossing operators are developed and embedded in the IMO-ABC algorithm. Meanwhile, a variable neighborhood local search strategy and a global search strategy, which could enhance exploitation and exploration, respectively, are proposed. Finally, representative maps including a real environment map are employed for simulation tests. The effectiveness of the proposed strategies is verified through numerous comparisons and statistical analyses. Simulation results show that the proposed IMO-ABC yields better solutions with respect to hypervolume and set coverage metrics for the later decision-maker.

The aim of college education is not only to teach students professional knowledge and skills but also to develop their self-regulated learning (SRL) ability, which has great significance for their lifelong development. This study aims to investigate the roles played by professional identity, intrinsic motivation, and sense of school belonging in improving SRL ability among college students. Mediation and moderated mediation analyses were employed to analyze a sample of 619 college students. The findings suggest that intrinsic motivation mediates the relationship between professional identity and SRL ability, and that sense of school belonging moderates not only a direct link between professional identity and SRL ability but also an indirect association between intrinsic motivation and SRL ability. Students with a high sense of school belonging show a stronger influence of professional identity and intrinsic motivation on improving SRL ability than those with a low sense of school belonging. Therefore, promoting professional identity and intrinsic motivation can be particularly beneficial for students with a strong sense of school belonging in improving SRL ability.

Abstract Sertoli cells (SCs) support and nourish germ cells (GCs) through their crosstalk during spermatogenesis. However, the underlying epigenetic mechanism that ensures SCs’ functions in this process remains unclear. Here, we report that UHRF1, a critical epigenetic regulator, is mainly expressed in human and mouse pre-mature SCs, and is essential for establishing Sertoli-Germ cell crosstalk. SC-specific UHRF1 knockout mice exhibit complete sterility with Sertoli cell (SC) proliferation and differentiation aberrance, blood-testis barrier (BTB) disruption, and immature germ cell (GC) sloughing. RNA sequencing and Whole Genome Bisulfite Sequencing (WGBS) revealed that many extracellular matrix (ECM)-related genes (e.g., Timp1, Trf, and Spp1) appeared upregulated with the DNA hypomethylation status in UHRF1-deficient SCs. Strikingly, overexpression of Timp1, Trf, and Spp1 in SCs in vitro and in vivo could phenocopy the SC-specific UHRF1-deficient mice. Our data demonstrated that UHRF1 regulates the transcriptional program of ECM-related genes in SCs and establishes SC-GC crosstalk.

Nitrogen pollution in water bodies presents a serious threat to ecosystems due to its role in eutrophication. In this study, the aerobic denitrifying bacterium Alcaligenes faecalis was used as a model microorganism to investigate the optimal operating conditions for nitrogen removal from nitrogen-containing wastewater by Alcaligenes faecalis under different aeration modes, microbial dosages and C/N ratios. The results showed that the optimal aeration mode for efficient bacterial denitrification was 10 min of aeration with a 30 min interval, and the total nitrogen removal reached 87.82%. At different bacterial doses, NO3−–N was completely denitrified and NO2−–N accumulation levels were reduced, all of which resulted in significant denitrification, and the final total nitrogen removal efficiencies reached 86.39–98.50%. With an increase in the C/N ratio, the pollutant removal performance of denitrifying bacteria increased. When the C/N ratio was 17, the final rates of NO3−–N, TN and COD removal were 100%, 98.50% and 96.13%, respectively. At lower C/N ratios, the growth and metabolism of microorganisms were inhibited and fewer electron acceptors were available during the denitrification process, which seriously affected denitrification performance. In this study, the denitrification performance of aerobic denitrifying bacterium Alcaligenes faecalis was explored in experiments using changes in aeration mode, microbial dosage and C/N ratio, and the optimal operating conditions of Alcaligenes faecalis for treating nitrogenous wastewater were indicated. This provides technical support for Alcaligenes faecalis in improving the remediation effect of nitrogenous wastewater and provides a theoretical basis for further in-depth research on the performance of Alcaligenes faecalis in the future.

Abstract Background Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students’ career intentions. Information on the factors that may be associated with these students’ career change intentions is limited. Methods We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. Results A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic’s impact on the students’ lives were associated with changes in career choice (P

Accumulating epidemiological evidence shows that handgrip strength provides predictive potential in physical, mental, and reproductive health status. However, the associations between handgrip strength and semen characteristics have not been explored. We recruited 1382 eligible men at the Hubei Province Human Sperm Bank (Wuhan, China) who had their handgrip strength measured at recruitment and provided 6458 repeated semen specimens within a 6-month period. Semen characteristics, including semen volume, sperm motility parameters (immotility, nonprogressive motility, and progressive motility), and sperm concentration, were assessed. Mixed-effect models and restricted cubic spline functions were applied to investigate the relationship of handgrip strength with repeated measurements of semen characteristics. After adjusting for confounding factors, the mixed-effect models revealed that handgrip strength was positively associated with semen volume, sperm concentration, progressive motility, total motility, and total count (all P for trend < 0.05). Compared to men in the lowest quartile, those in the highest quartile of handgrip strength had higher semen volume, sperm concentration, progressive motility, total motility, and total count, with measurements of 14.2% (95% confidence interval [CI]: 5.9%–23.2%), 19.5% (95% CI: 7.3%‒33.1%), 9.5% (95% CI: 3.4%‒15.9%), 8.8% (95% CI: 3.2%‒14.6%), and 36.4% (95% CI: 18.9%‒56.5%), respectively. These positive dose-response relationships were further confirmed in restricted cubic splines, where handgrip strength was modeled as a continuous variable. Handgrip strength, as an indicator of muscular function and strength, was positively associated with semen characteristics in a dose-dependent manner.

Abstract Background Keratins (KRTs) are intermediate filament proteins that interact with multiple regulatory proteins to initiate signaling cascades. Keratin 13 (KRT13) plays an important role in breast cancer progression and metastasis. The objective of this study is to elucidate the mechanism by which KRT13 promotes breast cancer growth and metastasis. Methods The function and mechanisms of KRT13 in breast cancer progression and metastasis were assessed by overexpression and knockdown followed by examination of altered behaviors in breast cancer cells and in xenograft tumor formation in mouse mammary fat pad. Human breast cancer specimens were examined by immunohistochemistry and multiplexed quantum dot labeling analysis to correlate KRT13 expression to breast cancer progression and metastasis. Results KRT13-overexpressing MCF7 cells displayed increased proliferation, invasion, migration and in vivo tumor growth and metastasis to bone and lung. Conversely, KRT13 knockdown inhibited the aggressive behaviors of HCC1954 cells. At the molecular level, KRT13 directly interacted with plakoglobin (PG, γ-catenin) to form complexes with desmoplakin (DSP). This complex interfered with PG expression and nuclear translocation and abrogated PG-mediated suppression of c-Myc expression, while the KRT13/PG/c-Myc signaling pathway increased epithelial to mesenchymal transition and stem cell-like phenotype. KRT13 expression in 58 human breast cancer tissues was up-regulated especially at the invasive front and in metastatic specimens (12/18) (p

Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.

Objective: To compare the risk of osteoporotic fractures between the urban and urban-rural fringe populations in southern China and to explore the effect of bone turnover markers on fracture risk.Methods: Epidemiological investigations were conducted in the urban and urban-rural fringe areas of southern China in June 2018. Residents aged 40 years and over who signed informed consent forms were included. Physical examination and questionnaire collection were completed. Bone turnover markers (BTMs) including osteocalcin (OC) and beta cross-linked C-telopeptide of type 1 collagen (β-CTX) were tested. Bone mineral density (BMD) of the femoral neck and lumbar vertebrae 1–4 were measured using dual energy X-ray absorptiometry. Fracture risk assessment tool (FRAX) values were calculated to show the probability of major osteoporotic fracture (PMOF) and probability of hip fracture (PHF) over the next 10 years.Results: A total of 1,051 participants were included in this study, including 553 in the urban areas and 498 in the urban-rural fringe areas. The average PMOF and PHF were 3.4 (2.3–5.4) % and .6 (.3–1.5) %, respectively. Compared with that in the urban populations, the femoral neck BMD in the urban-rural fringe populations was lower and FRAX values were generally higher, especially for women. FRAX values in various populations were mainly negatively correlated with lumbar and femoral neck BMD and were positively correlated with β-CTX; meanwhile, only PHF was negatively correlated with OC. After adjusting for sex, elevated β-CTX levels significantly increased the risk of high PMOF in various populations and increased the risk of high PHF in the urban-rural fringe populations. In particular, the risks of increased PMOF and PHF could increase by as much as 33 times and 19.5 times, respectively, in the urban-rural fringe areas.Conclusion: The urban-rural fringe populations in Southern China may be at risk of osteoporotic fracture. In addition to being related to BMD, the FRAX value also correlates with some BTMs. Combining FRAX with BMD, and BTMs may better predict the fracture risk.

A quantum eigensolver is designed under a multilayer cluster mean-field (CMF) algorithm by partitioning a quantum system into spatially-separated clusters. For each cluster, a reduced Hamiltonian is obtained after a partial average over its environment cluster. The products of eigenstates from different clusters construct a compressed Hilbert space, in which an effective Hamiltonian is diagonalized to determine certain eigenstates of the whole Hamiltonian. The CMF method is numerically verified in multispin chains and experimentally studied in a fully-connected three-spin network, both yielding an excellent prediction of their ground states.

The COVID-19 pandemic led higher education institutions to transition to online learning. The present study was designed to investigate students' self-regulated learning strategies on academic performance in online learning. We analyzed the differences in college students' self-regulated learning (SRL) strategies according to their grade point average (GPA). The study included 1,163 students at a distance education university in China. Two online questionnaires were used to determine online SRL strategies. GPA scores were obtained from the university exam database to determine academic performance. The analysis showed that there are great differences between different self-regulated strategies and between different students when accepting the online learning. The analysis also showed that self-evaluation, metacognitive self-regulation, and effort regulation were positive predictors of academic progress, besides, self-evaluation and effort regulation had mutual influence effect on the improvement of GPA in online learning. These data will help teachers, education policymakers, and education administrators adopt and implement online learning services to improve students' academic performance.

Abstract Background Recent studies highlight the regulatory role of arachidonate lipoxygenase5 (Alox5) and its metabolite 5‐hydroxyeicosatetraenoic acid (5‐HETE) in cancer tumorigenesis and progression. In this study, we analyzed the expression, biological function and the downstream signaling of Alox5 in gastric cancer. Methods Alox5 protein levels were measured using IHC and ELISA. Growth, migration and survival assays were performed. Phosphorylation of molecules involved in growth and survival signaling were analyzed by WB. Analysis of variance and t‐test were used for statistic analysis. Results Alox5 and 5‐HETE levels were upregulated in gastric cancer patients. ALOX5 overexpression or 5‐HETE addition activates gastric cancer cells and reduces chemotherapy’s efficacy. In contrast, ALOX5 inhibition via genetic and pharmacological approaches suppresses gastric cancer cells and enhances chemotherapy’s efficacy. In addition, Alox5 inhibition led to suppression of ERK‐mediated signaling pathways whereas ALOX5‐5‐HETE activates ERK‐mediated signaling in gastric cancer cells. Conclusions Our work demonstrates the critical role of ALOX5‐5‐HETE in gastric cancer and provides pre‐clinical evidence to initialize clinical trial using zileuton in combination with chemotherapy for treating gastric cancer.

In the field of self-regulated learning ability for college students, prior research usually neglected the role of parents when considering the physical distance between college and home. Indeed, an underlying describable driving force of learning remains embedded in the relationship between parents and students, even at the college stage. This study aimed to explore the relationships among perceived parental academic expectations, mastery goal orientation, self-reflection, and self-regulated learning ability of college students. Mediation and moderated mediation analyses were employed to analyze a sample of 691 college students. The results indicate that mastery goal orientation partially mediates the relationship between perceived parental academic expectations and self-regulated learning. In addition, self-reflection moderates the relationship between perceived parental academic expectations and self-regulated learning. The positive correlation between perceived parental academic expectation and self-regulated learning is stronger for students with low self-reflection than those with high self-reflection.

One significant source of decoherence in superconducting circuits is known as two-level systems (TLSs), found in amorphous oxide layers. These circuits can, however, also be utilized as spectral and temporal TLS probes. Comprehensive investigations on the physics of TLSs are now possible thanks to recent advancements in superconducting qubits. Here, we simultaneously measure the tunable Xmon qubit decoherence time as well as the resonance frequency for more than 3 days to investigate stochastic fluctuations. Time-domain Allan deviation and frequency-domain power spectral density analysis indicate that two TLSs in near resonance with the qubit are responsible for the fluctuations. From the extracted oscillation in T1 decay, we locate the two TLSs near the junctions.

Microvibrations are one of the main factors contributing to platform jitter and a decline in pointing stability and precision. Among various disturbance sources, reaction wheel assembly (RWA) is one of the most significant ones and has drawn the interest of numerous scholars. How to evaluate the influence of the disturbances of RWA on the pointing accuracy of a spacecraft is an arduous task because it involves multiple disciplines. The acquisition of the frequency response function (FRF) from the disturbance source to the sensitive payload is one of the most crucial stages in integrated modeling. Direct measurement of the FRF in the six directions is challenging because of the restricted room for RWA installation in a spacecraft, particularly in small satellites. In this paper, a general method based on the Hv algorithm to obtain the FRF is presented. This method only needs the RWA, itself, as an excitation source. Then, in order to acquire the FRF, we use an optical remote-sensing satellite as the research object. The peak positions of FRF obtained by different RWAs are basically the same, while the amplitudes are slightly different, indicating that this method is effective. This method takes into consideration the coupling between the RWA and the spacecraft, making it possible to multiply the RWA disturbance measured at a fixed interface with the FRF, to determine the image motion of the sensitive payload.

In real manufacturing environments, the number of automatic guided vehicles (AGV) is limited. Therefore, the scheduling problem that considers a limited number of AGVs is much nearer to real production and very important. In this paper, we studied the flexible job shop scheduling problem with a limited number of AGVs (FJSP-AGV) and propose an improved genetic algorithm (IGA) to minimize makespan. Compared with the classical genetic algorithm, a population diversity check method was specifically designed in IGA. To evaluate the effectiveness and efficiency of IGA, it was compared with the state-of-the-art algorithms for solving five sets of benchmark instances. Experimental results show that the proposed IGA outperforms the state-of-the-art algorithms. More importantly, the current best solutions of 34 benchmark instances of four data sets were updated.

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.

Hydrogels with adhesive properties have the potential for rapid haemostasis and wound healing in uncontrolled non-pressurized surface bleeding. Herein, a typical hydrogen bond-crosslinked hydrogel with the above functions was constructed by directly mixing solutions of humic acid (HA) and polyvinylpyrrolidone (PVP), in which the HA worked as a crosslinking agent to form hydrogen bonds with the PVP. By altering the concentration of HA, a cluster of stable and uniform hydrogels were prepared within 10 s. The dynamic and reversible nature of the hydrogen bonds gave the HA/PVP complex (HPC) hydrogels injectability and good flexibility, as well as a self-healing ability. Moreover, the numerous functional groups in the hydrogels enhanced the cohesion strength and interaction on the interface between the hydrogel and the substrate, endowing them with good adhesion properties. The unique chemical composition and cross-linking mechanism gave the HPC hydrogel good biocompatibility. Taking advantage of all these features, the HPC hydrogels obtained in this work were broadly applied as haemostatic agents and showed a good therapeutic effect. This work might lead to an improvement in the development of multifunctional non-covalent hydrogels for application to biomaterials.

ABSTRACTThe H7N9 influenza virus has been circulating in China for more than six years. The neuraminidase (NA) has gained great concern for the development of antiviral drugs, therapeutic antibodies, and new vaccines. In this study, we screened seven mouse monoclonal antibodies (mAbs) and compared their protective effects against H7N9 influenza virus. The epitope mapping from escape mutants showed that all the seven mAbs could bind to the head region of the N9 NA close to the enzyme activity sites, and four key sites of N9 NA were reported for the first time. The mAbs D3 and 7H2 could simultaneously inhibit the cleavage of the sialic acid of fetuin protein with large molecular weight and NA-XTD with small molecule weight in the NA inhibition experiment, prevent the formation of virus plaque at a low concentration, and effectively protect the mice from the challenge of the lethal dose of H7N9 virus.

PurposeThe Chinese Children’s Cancer Group developed the CCCG-NB-2014 study to formulate optimal treatment strategies for high-risk (HR) neuroblastoma (NB). The safety and efficacy of this protocol were evaluated.MethodPatients with newly diagnosed neuroblastoma and defined as HR according to the Children’s Oncology Group study were included. They were treated with a combination of chemotherapy, surgery, and radiotherapy. The treatment-related toxicities, response rate, 3-year progression-free survival (PFS), and overall survival (OS) were analyzed.ResultsOf 159 patients enrolled between 2014 and 2018, 80 were eligible, including 19 girls and 61 boys, with a median age of 3.9 years (range 0.9–11). After a median follow-up of 24 months (range 3–40), the median OS was 31.8 months, and 3-year OS was 83.8%. In multivariate analyses, the OS was affected by N-MYC amplification (hazard ratio 0.212, 95% confidence interval (CI) 0.049–0.910; p = 0.037) and giant tumor mass (hazard ratio 0.197, 95% CI 0.071–0.552; p = 0.002). The median 3-year PFS was 25.8 months, and 3-year PFS was 57.5%. The univariate analysis showed that only the giant tumor mass was associated with the outcome. Of the 13 deaths, 11 died from the rapid progression of the disease and two from treatment-related toxicities. The most common adverse reaction was chemotherapy-induced hematological toxicity.ConclusionThe PFS and OS reported in our study were similar to Western countries. The CCCG-NB-2014 protocol proved to be an efficient regimen with tolerable side-effect for the treatment of pediatric HR-NB.

Since some cases of human infections with H5N8 avian influenza virus have been reported and caused great concern in recent years, it is important to develop an effective vaccine for human use to prevent a potential H5N8 pandemic. In the present study, a vaccine candidate virus based on newly human-infected A/Astrakhan/3212/2020 H5N8 virus was constructed by reverse genetics (RG) technology. The immunogenicity of H5N8 whole virion inactivated vaccine was evaluated by various doses of vaccine antigen formulated with squalene-based adjuvant (AddaVax), aluminum hydroxide (Al(OH)3) or without adjuvant in mice. The results showed AddaVax-adjuvanted H5N8 inactivated vaccine could stimulate the mice to produce a stronger protective immune response with higher titers of IgG antibodies, hemagglutination inhibition (HI), neuraminidase inhibition (NI) and microneutralization (MN) antibodies than vaccine formulations with Al(OH)3 adjuvant or without adjuvant, and achieve a dose-sparing effect. Moreover, the AddaVax-adjuvanted formulation also exhibited potent cross-reactive response in HI antibodies against different clades of H5 viruses. A significant correlation and a curve fitting among HI, NI and MN were found by the correlation analysis to predict the protective effect of the vaccine. With these findings, our study demonstrates that AddaVax adjuvant can enhance the immunogenicity of H5N8 inactivated vaccine remarkably, and proposes an effective strategy for dealing with a potential H5N8 virus pandemic.

Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Emerging evidence suggests that microRNAs (miRNAs) are essential for the metabolic homeostasis of liver tissues. Many hepatic miRNAs located in the miR-379/miR-544 cluster were significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. However, the function of the miR-379/miR-544 cluster in the process of hepatic steatosis remains unclear. Here, we report that the novel function of miR-379/miR-544 cluster in regulating obesity-mediated metabolic dysfunction. Genetical mutation of miR-379/miR-544 cluster in mice displayed resistance to high-fat diet (HFD)-induced obesity with moderate hepatic steatosis and hypertriglyceridemia. In vitro studies revealed that silencing of miR-379 in human hepatocellular carcinoma (HepG2) cells ameliorated palmitic acid-induced elevation of cellular triglycerides, and overexpression of miR-379 had the opposite effect. Moreover, Igf1r (Insulin-like growth factor 1 receptor) and Dlk1 (Delta-like homolog 1) were directly targeted by miR-379 and miR-329, respectively, and elevated in the livers of the miR-379/miR-544 cluster knockout mice fed on HFD. Further transcriptome analyses revealed that the hepatic gene expressions are dysregulated in miR-379/miR-544 knockout mice fed with HFD. Collectively, our findings identify the miR-379/miR-544 cluster as integral components of a regulatory circuit that functions under conditions of metabolic stress to control hepatic steatosis. Thus, this miRNA cluster provides potential targets for pharmacologic intervention in obesity and NAFLD.

Previous studies have substantiated the pivotal role of emotions and teachers in student learning, but the underlying mechanism of teachers and emotions on academic engagement remains underexplored. The present study examined the mediating role of teacher support in the relationship between foreign language learning anxiety (FLLA) and academic engagement in online classrooms. Participants were 415 Chinese university students who completed an online questionnaire. The findings of structural equation modelling indicated that teacher support had a partial mediation effect between FLLA and academic engagement. FLLA exhibited a significant negative impact on academic engagement, both directly and indirectly via perceived teacher support. Through both direct and indirect effects, FLLA could explain 44.8% of the variation in academic engagement and the mediation effect accounted for 47.3% of the total effect. The practical implication is that foreign language teachers should extend more support for learners during online learning, and provide learners with feedback adapted to their emotions.

Background: A growing body of evidence has found links between endocrine disruptor phthalates and male reproductive disorders, but the mechanisms underlying these relationships are poorly known. Seminal plasma metabolomes may mediate associations of phthalate exposure with impaired semen quality. Objective: To identify seminal plasma metabolomes associated with poor semen quality and evaluate their associations with urinary phthalate metabolites among 660 Chinese adult men. Method: The seminal plasma metabolic profiles were acquired using an untargeted approach based on liquid chromatography-high resolution mass spectrometry. We explored the differences in seminal plasma metabolites between participants with poor and good semen quality and evaluated cross-sectional associations between discriminatory metabolic biomarkers and urinary phthalate metabolites. Results: Differences between poor and good semen quality groups were observed in relation to 25 seminal plasma metabolites, mostly related to the metabolism of polyunsaturated fatty acids (PUFA) and acylcarnitine (all p

Abstract Background Aberrant DNA damage of germ cells, which impairs spermatogenesis and lowers fertility, is an important factor contributing to male infertility. MicroRNAs (miRNAs) play a significant role in the expression and regulation of multiple genes during spermatogenesis. Our previous study found much lower miR-424 (murine homologue miR-322) levels in the seminal plasma of infertile patients with high DFI(DNA Fragmentation Index)than in the fertile group. However, the mechanism by which miR-322 regulates germ cells during spermatogenesis remains unknown. Methods In this study, we successfully established a GC-2 cell model of miR-322 downregulation resulting in impaired spermatogenesis. And the cell viability were measured using Cell Counting Kit-8 (CCK-8; Dojindo, Japan) and MTT (Sigma Aldrich, USA). Immunofluorescence assay was used to detect cell damage and the expression of apoptosis-related proteins were measured using real-time quantitative PCR and Western blot analysis. Target genes were predicted and verified by online database retrieval and Dual-luciferase reporter gene assay. Results We observed evident decreases in the cell viability of GC-2 cells along with remarkable increases in apoptosis after miR-322 inhibition. While the expression of apoptosis-related genes, including Bax and caspases 3, 9, and 8 greatly increased in GC-2 cells after miR-322 downregulation, that of the anti-apoptotic Bcl-2 gene decreased. Ddx3x was found to be the direct target of miR-322. MiR-424 was then detected in the seminal plasma of infertile patients with high DFI(DNA Fragmentation Index); this miRNA was down-regulated but Ddx3x was upregulated in the infertile group. Conclusion MiR-322 plays a key role in promoting GC-2 cell apoptosis by directly regulating Ddx3x expression. MiR-424 downregulation in infertile men may induce spermatogenic cell apoptosis and sperm DNA damage by directly acting on the target gene locus Ddx3x, resulting in male infertility.

The objective of this study was to develop pediatric physiologically based pharmacokinetic (PBPK) models for pantoprazole and esomeprazole. Pediatric PBPK models were developed by Simcyp version 15 by incorporating cytochrome P450 (CYP)2C19 maturation and auto‐inhibition. The predicted‐to‐observed pantoprazole clearance (CL) ratio ranged from 0.96–1.35 in children 1–17 years of age and 0.43–0.70 in term infants. The predicted‐to‐observed esomeprazole CL ratio ranged from 1.08–1.50 for children 6–17 years of age, and 0.15–0.33 for infants. The prediction was markedly improved by assuming no auto‐inhibition of esomeprazole in infants in the PBPK model. Our results suggested that the CYP2C19 auto‐inhibition model was appropriate for esomeprazole in adults and older children but could not be directly extended to infants. A better understanding of the complex interplay of enzyme maturation, inhibition, and compensatory mechanisms for CYP2C19 is necessary for PBPK modeling in infants.

With the trend of manufacturing globalization, distributed production has attracted wide attention from the industry and academia. Nevertheless, there has been little research on the distributed hybrid flowshop scheduling (DHFS) problem. To make up for the gap, this study aims to solve the DHFS problem, in which multiple factories with hybrid flowshop scheduling (HFS) problems are considered. This problem consists of two subproblems: 1) how to choose a factory for each job and 2) how to schedule all jobs within the assigned factories. To solve the DHFS problem, a mathematical model is formulated. Then, inspired by successful applications of brain storm optimization (BSO) algorithm in different fields, we try to solve the DHFS with a hybrid BSO (HBSO). In the proposed algorithm, firstly, a new approach to calculate the distance in the procedure of clustering is embedded. Then, a novel constructive heuristic based on the Nawaz-Enscore-Ham (NEH) method, called distributed NEH, is proposed. Moreover, an improved crossover operator based on the partial-mapped crossover (PMX) is designed for the distributed scheduling problem. Finally, the 20 large-scale instances based on the realistic production data are randomly generated to test the performance of the proposed algorithm. The experimental results verify that the proposed algorithm is efficient and effective for solving the considered DHFS problems in comparison with the other recently published efficient algorithms.

Maternal factors that modulate maternal-to-zygotic transition (MZT) are essential for the growth from specialized oocytes to totipotent embryos. Despite several studies, the mechanisms regulating epigenetic reprogramming during MZT remain largely elusive. UHRF1 plays a role in maintaining GC methylation in oocytes and early embryos. However, little is known about its role in mouse MZT. Here, we explored the function of maternal UHRF1 in zygotic genome regulation during early embryonic development in mice. We showed that the conditional knockout (cKO) of UHRF1 in either primordial or growing oocytes causes infertility but differentially affects early embryonic development. UHRF1 deficiency in primordial oocytes led to early embryonic developmental arrest at the two-cell stage, accompanied by significant alterations in global DNA and H3K4me3 methylation patterns. In comparison, UHRF1 ablation in growing oocytes significantly reduced developmental competence from two-cell embryos to blastocysts. At the transcriptional level, the absence of maternal UHRF1 led to aberrant transcriptional regulation of the zygotic genome during MZT at the two-cell stage. Furthermore, we observed that retrotransposable elements in UHRF1-deficient oocytes and embryos were not silenced properly; in particular, the LINE-1 and long terminal repeat (LTR) subfamily were activated abnormally. Collectively, the findings of our study reveal that maternal UHRF1 plays a critical role in establishing the correct epigenetic chromatin reprogramming of early embryos, regulating essential genes during MZT, and preserving genome integrity that drives early embryonic development in mice.

Background: Trihalomethanes (THMs) have demonstrated adverse effects on male reproductive systems in experimental animals, but human evidence has been inconsistent. Prior researches have been limited by small sample sizes and inadequate exposure assessment. Objectives: To investigate the association between blood THMs and repeated measurements of semen quality parameters among 1199 healthy men screened as potential sperm donors. Methods: We recruited healthy men presenting to the Hubei Province Human Sperm Bank from April to December 2017. At study entry, each participant provided a spot blood sample which was used to quantify blood concentrations of four THMs: chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM). The summary measures of exposure for brominated THMs (Br-THMs; molar sum of BDCM, DBCM and TBM) and total THMs (TTHMs; molar sum of TCM and Br-THMs) were also calculated. We used multivariable linear regression models to estimate the cross-sectional associations of tertiles of blood THM concentrations with semen quality parameters measured at study entry, and mixed-effect models to estimate the longitudinal associations accounting for repeated measures of semen quality, adjusting for relevant confounding factors. Results: In the cross-sectional analysis, several inverse dose-response relationships were observed across tertiles of blood TCM concentrations and sperm count, total motility and progressive motility, and between blood DBCM, and Br-THMs, and TTHMs and sperm count and concentration. The inverse associations of blood TCM, DBCM, Br-THMs and TTHMs with sperm count were confirmed in the longitudinal, repeated measure analysis. Conclusion: Our results suggest that exposure to THMs from drinking water may be related to decreased semen quality in young healthy men. Keywords: Blood samples, Disinfection by-products, Trihalomethanes, Semen quality, Epidemiology

In this paper, we address the steelmaking scheduling problems with multiple constrained resources. The objective is to minimize the maximum completion time. We consider the continuous casting constraint and resource constraints simultaneously. Based on the artificial bee colony (ABC) algorithm, we propose several heuristics and develop a discrete ABC (DABC) algorithm for the considered problem. In the proposed algorithm, a two-phase-based encoding mechanism is presented to create different searching abilities during different stages of evolution. Next, a decoding method considering the resource constraints is designed. A local search procedure is developed to utilize the two-phase encoding mechanism efficiently. Then, a global search heuristic is investigated to enhance the ability to escape from the local best. Finally, we test the proposed DABC algorithm by running it on sets of instances that are randomly generated based on realistic steelmaking production system. After detailed comparisons and statistical analysis, the competitive performance of the proposed DABC algorithm is verified.

Based on the analysis of the transmitter and receiver model of 802.11a WLAN system, a scheme of channel estimation，equalization and FPGA implementation based on the preamble of the OFDM system is proposed, including channel estimation and compensation. The circuit modules in the scheme are written in Verilog HDL language and they are simulated，complied and synthesized in the Xilinx programming software vivado 14.2.The result of the simulation indicates that all the modules run well and meet the requirement of the design.