Research progress on the fanconi anemia signaling pathway in non-obstructive azoospermia

Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli cell-only syndrome. Studies have shown that FA cross-linked anemia (FA) pathway is closely related to the occurrence of NOA. There are FA gene mutations in male NOA patients, which cause significant damage to male germ cells. The FA pathway is activated in the presence of DNA interstrand cross-links; the key step in activating this pathway is the mono-ubiquitination of the FANCD2-FANCI complex, and the activation of the FA pathway can repair DNA damage such as DNA double-strand breaks. Therefore, we believe that the FA pathway affects germ cells during DNA damage repair, resulting in minimal or even disappearance of mature sperm in males. This review summarizes the regulatory mechanisms of FA-related genes in male azoospermia, with the aim of providing a theoretical reference for clinical research and exploration of related genes

Genetic variants of EML1 and HIST1H4E in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival

Both in vivo and in vitro evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown. Methods: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients. Results: we identified two SNPs (EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, P=0.001) and 1.66 (1.22-2.26, P=0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets (P trendG and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS

Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies

Seismic Deformation Evaluation of High Concrete Face Rockfill Dam Based on Stochastic Dynamic Analysis Method

Most of the existing studies on high dams under seismic action use stable ground motions, which cannot simulate the non-stationary process of practical ground motions well. Although many scholars have studied the special characteristics of ground motion frequency and intensity lately, relatively few systematic studies have been carried out for the residual deformation of practical high dam projects. In this paper, considering the special characteristics of ground motions, 144 non-stationary stochastic seismic acceleration time histories are generated by the spectral expression-random function method, and stochastic dynamic calculations are carried out for four three-dimensional models of Gushui, Lava, Dashixia, and Ciha Gorge, respectively. We analyze the acceleration and residual deformation laws of four concrete face rockfill dams (CFRDs) based on the generalized probability density evolution method (GPDEM) and extreme value distribution theory. According to the results, the reference value of the dam body deformation of the 250 m panel under different seismic intensities is given, and the settlement at the dam crest is proposed. When the safety control standard is 1.0~1.1%, the ultimate seismic capacity of the 250 m face rockfill dam is 0.7~0.8 g

Seismic Deformation Evaluation of High Concrete Face Rockfill Dam Based on Stochastic Dynamic Analysis Method

Most of the existing studies on high dams under seismic action use stable ground motions, which cannot simulate the non-stationary process of practical ground motions well. Although many scholars have studied the special characteristics of ground motion frequency and intensity lately, relatively few systematic studies have been carried out for the residual deformation of practical high dam projects. In this paper, considering the special characteristics of ground motions, 144 non-stationary stochastic seismic acceleration time histories are generated by the spectral expression-random function method, and stochastic dynamic calculations are carried out for four three-dimensional models of Gushui, Lava, Dashixia, and Ciha Gorge, respectively. We analyze the acceleration and residual deformation laws of four concrete face rockfill dams (CFRDs) based on the generalized probability density evolution method (GPDEM) and extreme value distribution theory. According to the results, the reference value of the dam body deformation of the 250 m panel under different seismic intensities is given, and the settlement at the dam crest is proposed. When the safety control standard is 1.0~1.1%, the ultimate seismic capacity of the 250 m face rockfill dam is 0.7~0.8 g

Direct Probability Integral Method for Seismic Performance Assessment of Earth Dam Subjected to Stochastic Mainshock–Aftershock Sequences

Studying the impact of mainshock–aftershock sequences on dam reliability is crucial for effective disaster prevention measures. With this purpose in mind, a new method for stochastic dynamic response analyses and reliability assessments of dams during seismic sequences has been proposed. Firstly, a simulation method of stochastic seismic sequences is described, considering the dependence between mainshock and aftershock based on Copula function. Then, a novel practical framework for stochastic dynamic analysis is established, combined with the improved point selection strategy and the direct probability integration method (DPIM). The DPIM is employed on a nonlinear system with one degree of freedom and compared with Monte Carlo simulation (MCS). The findings reveal that the method boasts exceptional precision and efficiency. Finally, the seismic performance of a practical dam was evaluated based on the above method, which not only accurately estimates the response probability distribution and dynamic reliability of the dam, but also greatly reduces the required calculations. Furthermore, the impact of aftershocks on dam seismic performance is initially evaluated through a probability approach in this research. It is found that seismic sequences will significantly increase the probability of earth dam failure compared with sequences of only mainshocks. In addition, the influence of aftershocks on reliability will further increase when the limit state is more stringent. Specifically, the novel analysis method proposed in this paper provides more abundant and objective evaluation indices, providing a dynamic reliability assessment for dams that is more effective than traditional evaluation methods

Fabrication of a highly stable Nb2O5@C/CNTs based anolyte for lithium slurry flow batteries

Improving the stability of the anolyte and catholyte is crucial for the fabrication of high-performance lithium slurry flow batteries (LSFBs). To achieve an optimal slurry electrode for LSFBs, an anisotropic Nb2O5@C/CNTs nanocomposite was synthesized. The effects of active material content on the electrical and rheological behaviors of the slurry were studied systematically. An approximate bell-shaped curve depicts the variation trend of electronic conductivity under different Nb-based active material contents. The high aspect ratio of carbon nanotubes was found to be responsible for the formation of a conductive network in the slurry. The optimal matching point between active materials and KB increased from 8 wt% (Nb2O5@C) to 16 wt% (Nb2O5@C/CNTs). Under the condition that a KB percolation network was created, the as-prepared Nb2O5@C/CNTs anolyte delivers a high specific capacity of 217 mA h g(-1) and Coulombic efficiency > 92% in the flow reactor under a static mode. Moreover, the assembled flow reactor could work well under an intermittent flow mode, which indicates the feasibility of the as-prepared anolytes in a flow reactor. The fabrication of the highly stable Nb2O5@C/CNTs based anolyte will be helpful for the development of high energy density LSFBs with ultralong cyclability

Cultural Protection and Inheritance of Red Buildings from the Perspective of Rural Revitalization : A Case Study of the Former Site of "Third Line" Military Factory in Pengfang, Jiangxi Province

This paper makes an investigation and analysis of the existing red buildings in Pengfang Township, and puts forward the circular development model of "Red Building + Rural Tourism" after systematic arrangement. And through the dialectical perspective of the protection, inheritance, development and utilization of architectural culture under the revitalization of the countryside, this paper observes how the villages with red buildings help to boost the rural economy by integrating its own internal and external resources under the background of the great revival of the national rural traditional culture, so as to realize the protective development of rural red buildings

Black-Box Adversarial Attack on Time Series Classification

With the increasing use of deep neural network (DNN) in time series classification (TSC), recent work reveals the threat of adversarial attack, where the adversary can construct adversarial examples to cause model mistakes. However, existing researches on the adversarial attack of TSC typically adopt an unrealistic white-box setting with model details transparent to the adversary. In this work, we study a more rigorous black-box setting with attack detection applied, which restricts gradient access and requires the adversarial example to be also stealthy. Theoretical analyses reveal that the key lies in: estimating black-box gradient with diversity and non-convexity of TSC models resolved, and restricting the l0 norm of the perturbation to construct adversarial samples. Towards this end, we propose a new framework named BlackTreeS, which solves the hard optimization issue for adversarial example construction with two simple yet effective modules. In particular, we propose a tree search strategy to find influential positions in a sequence, and independently estimate the black-box gradients for these positions. Extensive experiments on three real-world TSC datasets and five DNN based models validate the effectiveness of BlackTreeS, e.g., it improves the attack success rate from 19.3% to 27.3%, and decreases the detection success rate from 90.9% to 6.8% for LSTM on the UWave dataset

RP-HPLC Characterization of Lupenone and β-Sitosterol in Rhizoma Musae and Evaluation of the Anti-Diabetic Activity of Lupenone in Diabetic Sprague-Dawley Rats

With the aim of characterizing the active ingredients lupenone and β-sitosterol in Rhizoma Musae samples a reversed-phase HPLC method for the separation of these two compounds in Rhizoma Musae samples was developed (regression coefficient &gt; 0.9996). The method was further applied to quantify lupenone and β-sitosterol content in Rhizoma Musae samples cultured in different growth environments. Different variables such as geographical location, growth stage, and harvest time, demonstrated differential effects on lupenone and β-sitosterol levels. Moreover, we determined the optimum conditions for cultivation and harvesting of Rhizoma Musae herbs. Lupenone administration caused a significant reduction in fasting blood glucose (FBG) levels in diabetic rats at doses of 1.78, 5.33, and 16.00 mg·kg−1·day−1 for 14 days, the glycated hemoglobin (HbA1c) levels of diabetic rats also significantly reduced at doses of 5.33, and 16.00 mg·kg−1·day−1, indicating a robust antidiabetic activity. To our knowledge, this is the first report of an optimized HPLC method successfully applied to quantify lupenone and β-sitosterol, and its applicability in optimizing Rhizoma Musae growth. Animal experiments also showed for the first time that lupenone from Rhizoma Musae has anti-diabetic activity