Integrated analysis of microRNA expression profiles and function network in mice testes after low dose lead exposure from early puberty.

There is evidence suggesting the participation of non-coding RNAs in male reproductive dysfunction induced by lead, and the significance of microRNAs has been highlighted recently because of their essential roles in gene regulatory networks. To comprehensively understand the functions of miRNA and the regulatory networks, RNA sequencing was carried out to obtain miRNA expression profiles in mice testes exposed to low dose Pb for 90 days at the onset of puberty. In total, 44 differentially expressed miRNAs with 26 up-regulated and 18 down-regulated were identified between 200 mg/L Pb group and control group (p < 0.05). Enrichment analysis confirmed that the target genes of DE miRNAs might participate in the metabolism of testicular cells. Furthermore, a miRNA-mRNA co-expression network consisting of 19 miRNAs and 106 mRNAs and a competing endogenous RNA network of lncRNA-miRNA-mRNA including 179 genes were established. Finally, the expressions of 4 miRNAs (mmu-miR-451a, mmu-miR-133a-3p, mmu-miR-1a-3p and mmu-miR-486a-3p) and 4 mRNAs (Gramd1b, Tcf7l2, Mov10 and Srcin1) involved in regulatory networks were verified by RT-qPCR. In conclusion, our research might provide targets for the mechanism studies of miRNAs in reproductive toxicity of Pb.

Zinc Supplementation Reduces Testicular Cell Apoptosis in Mice and Improves Spermatogenic Dysfunction Caused by Marginal Zinc Deficiency.

Zinc (Zn) is an important trace element in the human body and plays an important role in growth, development, and male reproductive functions. Marginal zinc deficiency (MZD) is common in the human population and can cause spermatogenic dysfunction in males. Therefore, the aim of this study was to investigate methods to improve spermatogenic dysfunction caused by MZD and to further explore its mechanism of action. A total of 75 4-week-old male SPF ICR mice were randomly divided into five groups (control, MZD, MZD + ZnY2, MZD + ZnY4, and MZD + ZnY8, 15 mice per group). The dietary Zn content was 30 mg/kg in the control group and 10 mg/kg in the other groups. From low to high, the Zn supplementation doses administered to the three groups were 2, 4, and 8 mg/kg·bw. After 35 days, the zinc content, sperm quality, activity of spermatogenic enzymes, oxidative stress level, and apoptosis level of the testes in mice were determined. The results showed that MZD decreased the level of Zn in the serum, sperm quality, and activity of spermatogenic enzymes in mice. After Zn supplementation, the Zn level in the serum increased, sperm quality was significantly improved, and spermatogenic enzyme activity was restored. In addition, MZD reduced the content of antioxidants (copper-zinc superoxide dismutase (Cu-Zn SOD), metallothionein (MT), and glutathione (GSH) and promoted malondialdehyde (MDA) production. The apoptosis index of the testis also increased significantly in the MZD group. After Zn supplementation, the level of oxidative stress decreased, and the apoptosis index in the testis was reduced. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) showed that the expression of B-cell lymphoma-2 (Bcl-2) mRNA and Bcl-2/BCL2-associated X (Bax) in the control group decreased in testicular cells, and their expression was restored after Zn supplementation. The results of this study indicated that Zn supplementation can reduce the level of oxidative stress and increase the ability of testicular cells to resist apoptosis, thereby improving spermatogenic dysfunction caused by MZD in mice.

Research on and Model Analysis of Flexural Mechanical Properties of Basic Magnesium Sulfate Cement Concrete Beams.

This study presents a comprehensive investigation into the mechanical properties of Basic Magnesium Sulfate Cement Concrete (BMSC) in comparison to Ordinary Portland Cement Concrete (OPC) within reinforced concrete components. The main objective is to evaluate BMSC's applicability for practical engineering purposes, with a focus on its with early high strength, improved toughness, and superior crack resistance compared to conventional concrete. Experimental procedures involved fabricating beam specimens using OPC concrete with a C40 strength grade, alongside BMSC beams with varying strength grades (C30, C40, and C50). These specimens underwent bending resistance tests to analyze crack patterns and mechanical characteristics. The findings reveal that BMSC beams demonstrate enhanced bending and tensile properties at equivalent strength grades compared to OPC beams. Particularly, cracking mainly occurred at the mid-span region of BMSC beams, characterized by narrower cracks, indicating superior crack resistance. However, it was noted that the toughness of BMSC beams decreases as the strength grade increases. The maximum mid-span deflection of the BMSC test beam was smaller than that of the OPC test beam, which was 3.8 mm and 2.6 mm, respectively. The maximum crack width of the OPC beam was 4.7 times that of the BMSC beam. To facilitate practical implementation, the study developed calculation models for estimating the crack bending distance and ultimate bending distance in BMSC beams, offering valuable tools for engineering design and optimization. Overall, this research provides significant insights into the mechanical behavior of BMSC, presenting potential advantages for structural engineering applications.

Application of Multi-Rod Constructs for the Revision of Thoracolumbar Fractures.

OBJECTIVE: The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi-rod constructs in the revision of thoracolumbar fractures. METHODS: Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi-rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow-up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow-up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). RESULTS: The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow-up period. The paired t-test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre-revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post-revision and last follow-up (p = 0.551). VAS and ODI were greatly improved at the last follow-up. CONCLUSION: The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi-rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Design and Synthesis of 2-(5-Phenylindol-3-yl)benzimidazole Derivatives with Antiproliferative Effects towards Triple-Negative Breast Cancer Cells by Activation of ROS-Mediated Mitochondria Dysfunction.

Benzimidazole derivatives are widely studied because of their broad-spectrum biological activity, such as antitumor properties and excellent fluorescence performance. Herein, two types of 2-(5-phenylindol-3-yl)benzimidazole derivatives (1 a-1 h and 2 a-2 e) were rationally designed and synthesized. When these compounds were investigated in vitro anti-screening assays, we found that all of them possessed antitumor effect, in particular compound 1 b, which showed an outstanding antiproliferative effect on MDA-MB-231 cells (IC50 ≈2.6 µm). A study of the drug action mechanisms in cells showed that the antitumor activity of the compounds is proportional to their lipophilicity and cellular uptake; the tested compounds all entered the lysosome of MDA-MB-231 cells and caused changes in the levels of reactive oxygen species (ROS), and then caused mitochondrial damage. Apparent differences in the ROS levels for each compound suggest that the lethality of these compounds towards MDA-MB-231 cells is closely related to the ROS levels. Taken together, this study not only provides a theoretical basis for 2-(5-phenylindol-3-yl)benzimidazole anticarcinogens but also offers new thinking on the rational design of next-generation antitumor benzimidazole derivatives.

[Study on chemical constituents from Mycale parishi].

Three alkaloids have been isolated from Mycale parishi collected from Naozhou Island of Zhanjiang in China, their structure were identified as 1-(4-Hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine- 2,4-dione(I), 1H-Pyrimidine-2,4-dione(II), Pentacosanoic acid (2-hydroxy-1-hydroxymethyl-heptadec-3-enyl)-amide(III), respectively on the basic of the spectral data of MS, 1H NMR, 13CNMR.

HIV-1 diversity and drug-resistant mutations in infected individuals in Changchun, China.

OBJECTIVES: Human immunodeficiency virus type 1 (HIV-1) infection has been detected in all provinces of China. Although epidemiological and phylogenetic studies have been conducted in many regions, such analyses are lacking from Jilin province in northeastern China. METHOD: Epidemiological and phylogenetic analyses, as well as detection of drug-resistant mutations, were conducted on 57 HIV-1 infected patients from Changchun city identified and confirmed through annual surveillance by local Centers for Disease Control in Jilin province of northeastern China in 2012. RESULTS: Sexual contact was determined to be the major pathway for HIV-1 transmission in Jilin, where hetero- and homosexual activities contributed almost equally. Phylogenetic analyses detected multiple subtypes of HIV-1 including subtype G circulating in Jilin, with multiple origins for each of them. Both subtype B and CRF01_AE were dominant, and evidence of subtype B transmitting between different high-risk groups was observed. Mutations in the viral protease at position 71 indicated the presence of a selective pressure. Several drug-resistant mutations were detected, although they were predicted with low-level resistance to antiviral treatments. CONCLUSIONS: Information from this study fills the gap in knowledge of HIV-1 transmission in Changchun city, Jilin province, China. By revealing the origin and evolutionary status of local HIV-1 strains, this work contributes to ongoing efforts in the control and prevention of AIDS.