Sperm differentiation requires specific protein transport for correct sperm tail formation and head shaping. A transient microtubular structure, the manchette, appears around the differentiating ...spermatid head and serves as a platform for protein transport to the growing tail. Sperm flagellar 2 (SPEF2) is known to be essential for sperm tail development. In this study we investigated the function of SPEF2 during spermatogenesis using a male germ cell-specific
knockout mouse model. In addition to defects in sperm tail development, we observed a duplication of the basal body and failure in manchette migration resulting in an abnormal head shape. We identified cytoplasmic dynein 1 and GOLGA3 as novel interaction partners for SPEF2. SPEF2 and dynein 1 colocalize in the manchette and the inhibition of dynein 1 disrupts the localization of SPEF2 to the manchette. Furthermore, the transport of a known SPEF2-binding protein, IFT20, from the Golgi complex to the manchette was delayed in the absence of SPEF2. These data indicate a possible novel role of SPEF2 as a linker protein for dynein 1-mediated cargo transport along microtubules.
The proline-type organocatalysts has been efficiently employed to catalyze a wide range of asymmetric transformations; however, there are still many synthetically useful and challenging ...transformations that remain unachievable in an asymmetric fashion. Herein, a chiral bifunctional organocatalyst with a spirocyclic pyrrolidine backbone-derived containing fluoro-alkyl and aryl sulfonamide functionalities, are designed, prepared, and examined in the asymmetric Mannich/acylation/Wittig reaction sequence of 3,4-dihydro-β-carboline with acetaldehyde, acyl halides, and Wittig reagents. As a result, the spirocyclic pyrrolidine trifluoromethanesulfonamide catalyst can facilitate this versatile sequence as demonstrated by 18 examples displaying excellent enantioselectivity (up to 94% ee), as well as moderate to good yields (up to 54% over 3 steps). As a practical application, the asymmetric total synthesis of naucleofficine I (1a) and II (1b) in ten steps have been accomplished.
Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from
Nannf. var.
(Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal ...immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of
and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
Compression index Cc is an essential parameter in geotechnical design for which the effectiveness of correlation is still a challenge. This paper suggests a novel modelling approach using machine ...learning (ML) technique. The performance of five commonly used machine learning (ML) algorithms, i.e. back-propagation neural network (BPNN), extreme learning machine (ELM), support vector machine (SVM), random forest (RF) and evolutionary polynomial regression (EPR) in predicting Cc is comprehensively investigated. A database with a total number of 311 datasets including three input variables, i.e. initial void ratio e0, liquid limit water content wL, plasticity index Ip, and one output variable Cc is first established. Genetic algorithm (GA) is used to optimize the hyper-parameters in five ML algorithms, and the average prediction error for the 10-fold cross-validation (CV) sets is set as the fitness function in the GA for enhancing the robustness of ML models. The results indicate that ML models outperform empirical prediction formulations with lower prediction error. RF yields the lowest error followed by BPNN, ELM, EPR and SVM. If the ranges of input variables in the database are large enough, BPNN and RF models are recommended to predict Cc. Furthermore, if the distribution of input variables is continuous, RF model is the best one. Otherwise, EPR model is recommended if the ranges of input variables are small. The predicted correlations between input and output variables using five ML models show great agreement with the physical explanation.
This paper suggests a novel modelling approach using machine learning (ML) technique. The performance of five commonly used machine learning (ML) algorithms, i.e. back-propagation neural network (BPNN), extreme learning machine (ELM), support vector machine (SVM), random forest (RF) and evolutionary polynomial regression (EPR) in predicting Cc is comprehensively investigated. The results indicate that ML models outperform empirical prediction formulations with lower prediction error. RF yields the lowest error followed by BPNN, ELM, EPR and SVM. If the ranges of input variables in the database are large enough, BPNN and RF models are recommended to predict Cc. Furthermore, if the distribution of input variables is continuous, RF model is the best one. Display omitted
•Novel machine learning based models are proposed for predicting compression index of clays.•The performance of five commonly used machine learning algorithms in predicting Cc is comprehensively investigated.•BPNN and RF models are recommended to predict the compression index of clays.
•Constructing a complex (1) with precise structures by introducing luminescent groups triphenylphosphine (TPA), is used for treatment and imaging.•Within 0.5 h, 1 can be distributed into cells, ...performing effective cell imaging.•1 can be used for CDT, promoting oxidative stress and causing cell apoptosis.
The combination of imaging and treatment is the fundamental strategy for achieving precise anticancer treatment. This article constructs a copper(I) complex (1) by aminourea derivative containing triphenylamine (TPA). 1 with precise structure, can be used for cell imaging and chemodynamic therapy (CDT). Within 0.5 h, 1 can be distributed into the mitochondria of T24 cells, performing effective cell imaging and then promoting oxidative stress and causing cell apoptosis.
A precise complex with luminescent triphenylphosphine (TPA) group, is used for the effective cell imaging, promoting oxidative stress and causing cell apoptosis. Display omitted
In this study, two Ni(II) complexes, namely Ni(HL1)₂(OAc)₂ (
) and Ni(L2)₂ (
) (where HL1 and HL2 are (
)-1-((1-(2-hydroxyethyl)-1
-pyrazol-5-ylimino)methyl)-naphthalen-2-ol) and (
...)-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-1
-pyrazole-4-carboxylate, respectively), were synthesized and characterized by X-ray crystallography, Electrospray Ionization Mass Spectrometry (ESI-MS), elemental analysis, and IR. Their uptake in biological macromolecules and cancer cells were preliminarily investigated through electronic absorption (UV-Vis), circular dichroism (CD) and fluorescence quenching measurements. Bovine serum albumin (BSA) interaction experiments were investigated by spectroscopy which showed that the complexes and ligands could quench the intrinsic fluorescence of BSA through an obvious static quenching process. The spectroscopic studies indicated that these complexes could bind to DNA via groove, non-covalent, and electrostatic interactions. Furthermore, in vitro methyl thiazolyl tetrazolium (MTT) assays and Annexin V/PI flow cytometry experiments were performed to assess the antitumor capacity of the complexes against eight cell lines. The results show that both of the complexes possess reasonable cytotoxicities.
Androgen receptor (AR) is regulated by SUMOylation at its transactivation domain. In vitro, the SUMOylation is linked to transcriptional repression and/or target gene-selective regulation. Here, we ...generated a mouse model (ArKI) in which the conserved SUMO acceptor lysines of AR are permanently abolished (Ar
). ArKI males develop normally, without apparent defects in their systemic androgen action in reproductive tissues. However, the ArKI males are infertile. Their spermatogenesis appears unaffected, but their epididymal sperm maturation is defective, shown by severely compromised motility and fertilization capacity of the sperm. Fittingly, their epididymal AR chromatin-binding and gene expression associated with sperm maturation and function are misregulated. AR is SUMOylated in the wild-type epididymis but not in the testis, which could explain the tissue-specific response to the lack of AR SUMOylation. Our studies thus indicate that epididymal AR SUMOylation is essential for the post-testicular sperm maturation and normal reproductive capability of male mice.
The plastic work-heat conversion coefficient is one key parameter for studying the work-heat conversion under dynamic deformation of materials. To explore this coefficient of 7075-T651 aluminum alloy ...under dynamic compression, dynamic compression experiments using the Hopkinson bar under four groups of strain rates were conducted, and the temperature signals were measured by constructing a transient infrared temperature measurement system. According to stress versus strain data as well as the corresponding temperature data obtained through the experiments, the influences of the strain and the strain rate on the coefficient of plastic work converted to heat were analyzed. The experimental results show that the coefficient of plastic work converted to heat of 7075-T651 aluminum alloy is not a constant at the range of 0.85–1 and is closely related to the strain and the strain rate. The change of internal structure of material under high strain rate reduces its energy storage capacity, and makes almost all plastic work convert into heat.