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Diabetic cardiomyopathy (DCM) is considered to be a critical contributor to the development of heart failure. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has been shown to prevent cardiovascular events and reduce the incidence of heart failure in randomized clinical trials. However, the mechanism of how EMPA prevents DCM is poorly understood. To study the potential mechanisms involved in the therapeutic effects of EMPA, we assessed the protective effects of EMPA on myocardial injury in type 2 diabetic db/db mice and H9C2 cardiomyocytes. 9–10-week-old male db/db mice were treated with EMPA (10 mg/kg) via oral gavage daily for 20 weeks. Afterward, cardiac function of treated mice was evaluated by echocardiography, and pathological changes in heart tissues were determined by histopathological examination and western blot assay. EMPA markedly reduced blood glucose levels, improved insulin tolerance, and enhanced insulin sensitivity of db/db mice. In addition, EMPA significantly prevented cardiac dysfunction, inhibited cardiac hypertrophy and fibrosis, and reduced glycogen deposition in heart tissues. Furthermore, EMPA improved diabetes-induced oxidative stress and mitochondrial dysfunction in both heart tissues of db/db mice and palmitate exposed H9C2 cells. EMPA significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genetic targets in cardiac tissue of type 2 diabetic db/db mice and H9C2 cells. EMPA also downregulated the expression of mitochondrial fission-related proteins and upregulated the expression of mitochondrial fusion-related proteins. Collectively, these findings indicate that EMPA may prevent DCM via attenuating oxidative stress and improving mitochondrial function in heart tissue.

Temporal absences in observation records lead to release losses during the source term inversions of atmospheric radionuclide emissions. Consequently, objectively-estimated source terms for the Fukushima accident contain fewer release details and present large discrepancies when compared with the expert-judged one. This paper describes an objective method that can adaptively recover the missing releases caused by the temporal absences of observations. The proposed method assumes that the accident releases of radionuclides are piecewise-constant and comprise both peaks and constant releases. The missing releases are adaptively recovered as either peaks or constant releases by minimizing the total variation of the estimated source term. The proposed method is applied to the Fukushima accident and evaluated against regional airborne and deposited

Peng Feng,1,* Yuchen Li,2,* Zhijie Tian,1,* Yuan Qian,1 Xingyu Miao,1 Yuelin Zhang3 1Neurosurgery, Shaanxi Provincial People’s Hospital, Xian, 710068, People’s Republic of China; 2Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 3Xi’an Medical University, Xian, 710021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingyu Miao; Yuelin Zhang, Email miaoxyu@163.com; xyyxyfp@163.comBackground: High-grade glioma is a type of heterogeneous lethal brain tumor most common in adults. At present, immune checkpoint inhibitors (ICIs) are being considered for first-line therapeutics for malignant GBM. Nonetheless, molecular markers for malignant GBM are unavailable at present. As a result, it is important to explore molecular markers related to immunity for GBM.Materials and Methods: The present study adopted a deconvolution algorithm for quantifying immunocyte composition and measuring gene expression, and used weighted gene co-expression network analysis (WGCNA) to analyze GBM expression data obtained from Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) databases. Thereafter, key CD8+ T cell infiltration-related genes and modules were identified, and database analysis was conducted to verify the therapeutic and immune features of the selected genes.Results: From this study, CD8+ T cell-related modules were identified. By using consistent clustering analysis, two panels of genes (red and green) with the highest correlation with CD8+ T cells infiltration were used to construct high-, low-expression groups, silent and/or mixed group of T cell infiltrations. In the high and low CD8+ T cell infiltration groups, a total of 535 differential genes were obtained, of which ten genes (RPS5, RPS6, FAU, RPS19, RPS23, RPS15A, RPS29, RPS14, RPS16, RPS27A) were identified through protein–protein interactions and co-expression network analysis. Post Cox regression and Kaplan–Meier (K-M) survival analysis, RPS5, RPS6, and RPS16 were selected as candidate prognostic biomarkers related to CD8+ T cells.Conclusion: The three associated genes RPS5, RPS6, and RPS16 were markedly related to degree of T cell infiltration and immune-related activated. We identified their potential biomarkers and therapeutic targets associated with the extent of CD8+ T cell infiltration in GBM.Keywords: prognosis, mutation, glioblastoma, gene, WGCNA

"Didn't understand or not fully understand" is the most common situation that students experience when they learn medical biochemistry and molecular biology (MBMB). Therefore, the primary task of teaching MBMB is to help students overcome the difficulties in "conceptual understanding." The core of the solution to these problems lies in the acquisition and application of cognitive skills. The key to applying Ausubel cognitive assimilation theory (A's CAT) is to expand the knowledge capacity of students' cognitive structure through the purposeful "production" and employment of advanced organizers, with which students can replace "rote learning" with "meaningful learning" and ultimately develop an interest in MBMB courses. The results showed that the application of A's CAT did not only encourage the students to use cognitive skills to learn and understand MBMB knowledge and overcome the barrier to learning that results from the characteristics of the MBMB course, but also expanded and deepened the MBMB course contents. As a branch of learning theory, A's CAT provides practical methods for the several hypotheses of learning theory. Among these, the advanced organizer strategy realizes the organization and reorganization of new knowledge; the progressive differentiation strategy reduces the difficulty of complex and abstract knowledge; the implementation of the advanced organizer strategy and integrative reconciliation strategy forms the concept map. Taken together, the application of A's CAT includes cognitive strategy and metacognitive strategy when the cognitive process is conducted in a meaningful way. More importantly, application of A's CAT guides students to participate in active learning and builds "scaffolding" for the teaching/learning MBMB of student-centered goals.

Stem cells, which are a class of cells with self-renewal capacity and multipotency of differentiation, play a critical role in tissue maintenance and regeneration in the whole life span of multicellular organism. With the recent researches about stem cell, it is realized that the aging and depletion of stem cells are closely related to organ aging and the occurrence of aging-related diseases, such as cardiovascular and cerebrovascular diseases, autoimmune diseases, and Alzheimer’s disease. Thus, understanding the molecular mechanisms of stem cell aging will be important for developing new therapies for aging-related diseases. There are many intrinsic and extrinsic factors promoting stem cell aging. Oxidative stress has been recognized as the major cause of stem cell aging. Oxidative stress is the result of an excessive production of reactive oxygen species (ROS) and an impairment of the antioxidant defense systems. Excessive production of ROS and insufficient cellular antioxidant trigger a variety of aging-related pathways to induce stem cell senescence and aging. In this chapter, we summarized the biologic features of stem cell aging and discussed how oxidative stress affects stem cell aging and the main signal pathways of stem cell aging triggered by oxidative stress. We further explored how stem cells manage ROS accumulation and adapt to oxidative stress. Finally, we discussed the potential strategies against stem cell aging by controlling oxidative stress.

The radioactive aerosols are produced during the operation of nuclear power plants will cause certain harm to human body. Dry deposition is one of the important factors affecting the aerosols deposition to the ground, and radioactive aerosols and common aerosols have similar properties in terms of dry deposition. Based on the similarity theory, with the help of the newly built environmental wind tunnel of the China Institute for Radiation Protection, with a part of a nuclear power plant site as a research object, and the wind tunnel simulation experiment of aerosol dry deposition characteristics was carried out in groups. The particle dynamic analyzer (PDA) was used to measure and calculate the dry deposition velocity of aerosol particles, and the results are grouped, analyzed and discussed. The research results show that when the variables are controlled, when the underlying surfaces are the same, compared with aerosol particles with particle sizes of 0-2 μm and 2-5 μm, the dry deposition velocity of aerosol particles greater than 5 μm is more likely to change with the increase of wind speed.

In this paper, the effects of different lateral offset directions on the microstructure and mechanical properties of the welded joints of 2A14-T6 aluminum alloy during friction stir welding (FSW) were studied. The results indicate that the center of the weld nugget (WN) always coincides with the center of the welding tool. There is some influence on the shape of the WN when the offset condition is present. The movement of the location of the WN with the offset of the welding tool changes the location of the initial contact surface (ICS), resulting in the change of the severe level of stirring at the ICS and the pressure at the joint root. There are varying degrees of lack of penetration when the welding tool shifts to the retreating side (RS) and the advancing side (AS) respectively. The presence of the defects has an important influence on the mechanical property and fracture, especially when the welding tool shifts to the AS. The joint performance has obvious reduction. In summary, the quality of the joint is more sensitive to the condition of AS offset.

This paper investigated the effects of calcium formate and methacrylic acid combined with cement paste powder on flowability, setting time, and mechanical strength of cement mortar. The effects of curing temperature and water-cement ratio on the hydration of cement mortar incorporating these two double-component early strength agents were also studied. Experimental results show that the 0.5, 1, 3 and 28-day compressive strength increased by 96.7% (89.3%), 81.7% (75.6%), 74.7% (67.4%) and 50.1% (49.9%) when 1.0% calcium formate (or 0.5% methacrylic acid) combined with 1.0% cement paste powder. These two types of double-component early strength agents presented an excellent synergistic effect. Higher curing temperature can accelerate the early hydration of cement but has a negative impact on the later strength. X-ray diffraction (XRD), Fourier transformation infrared spectroscope (FTIR), mercury intrusion porosimeter (MIP), and scanning electron microscope (SEM) results show that combined accelerating admixtures can accelerate the hydration of cement and decrease the porosity of cement mortar. Finally, the cost evaluation indicates that double-component early strength agents are applicable to manufacture high early-age strength cement-based materials.

Spermine oxidase (Smox) is a member of the polyamine oxidases and has been demonstrated to be involved in ischemic brain damage. In this study, we found that Smox expression was increased in a rat middle cerebral artery occlusion (MCAO) model and in cultured primary neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Smox downregulation by the adeno-associated virus RNA interference system significantly reduced the MCAO-induced brain infarct volume and neurological deficits and decreased neuronal apoptosis and inflammatory reactions. In addition, significant microglial activation and increased IL-6 and TNF-α expression were observed in microglia treated with supernatant from neurons after OGD/R. However, a significant reduction in microglial activation as well as IL-6 and TNF-α expression was observed in microglia treated with supernatant from Smox downregulated neurons after OGD/R. Therefore, the results indicated that Smox is an important mediator of cerebral ischemia injury and may be a therapeutic target for cerebral ischemia patients.

Herein, we report the effects of gap variation upon the joint quality and thermomechanical behaviour of 2A14-T6 aluminium alloy friction stir butt welding. Based on the optimal weld pitch, gap-free and variable gap (from 0 to 2 mm in the weld) friction stir welding (FSW) experiments were conducted. The results indicate that welds without metallurgical defects were obtained up to a butt gap of 0.8 mm; however, voids and tunnel defect occurred at gap widths of 1.6 and 2 mm, respectively; moreover, the results showed that joint efficiency began to sharply decrease when the gap exceeded 1.6 mm. Furthermore, the thermomechanical model of varied gap FSW showed when the gap exceeded 0.8 mm, the material transferred by the tool would not completely fill the cavity formed by the pin’s forward motion. Finally, the gap-tolerance window for FSW was evaluated in terms of welding defects, joint efficiency, and thermomechanical behaviour.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future.

Salt-alkali is the main threat to global crop production. The functioning of phosphorus (P) in alleviating damage to crops from saline-alkaline stress may be dependent on the variety of crop but there is little published research on the topic. This pot experiment was conducted to study if P has any effect on rice (Oryza sativa L.) yield, dry matter and P accumulation and translocation in salt-alkaline soils. Plant dry weight and P content at heading and harvest stages of two contrasting saline-alkaline tolerant (Dongdao-4) and sensitive (Tongyu-315) rice varieties were examined under two saline-alkaline (light versus severe) soils and five P supplements (P0, P50, P100, P150 and P200 kg ha−1). The results were: in light saline-alkaline soil, the optimal P levels were found for P150 for Dongdao-4 and for P100 for Tongyu-315 with the greatest grain dry weight and P content. Two rice varieties obtained relatively higher dry weight and P accumulation and translocation in P0. In severe saline-alkaline soil, however, dry weight and P accumulation and translocation, 1000-grain weight, seed-setting rate and grain yield significantly decreased, but effectively increased with P application for Dongdao-4. Tongyu-315 showed lower sensitivity to P nutrition. Thus, a more tolerant variety could have a stronger capacity to absorb and translocate P for grain filling, especially in severe salt-alkaline soils. This should be helpful for consideration in rice breeding and deciding a reasonable P application in saline-alkaline soil.

Salt-alkaline stress generally leads to soil compaction and fertility decline. It also restricts rice growth and phosphorus acquisition. In this pot experiment, two relatively salt-alkaline tolerant (Dongdao-4 and Changbai-9) and sensitive (Changbai-25 and Tongyu-315) rice genotypes were planted in sandy (control) and salt-alkaline soil to evaluate the characteristics of dry matter and phosphorus assimilation and translocation in rice. The results showed that dry matter and phosphorus assimilation in rice greatly decreased under salt-alkaline stress as the plants grew. The translocation and contribution of dry matter and phosphorus to the grains also increased markedly; different performances were observed between genotypes under salt-alkaline stress. D4 and C9 showed higher dry matter translocation, translocation efficiency and contribution of dry matter assimilation to panicles than those of C25 and T315. These changes in D4 and C9 indexes occurred at low levels of salt-alkaline treatment. Higher phosphorus acquisition efficiency of D4 and C9 were also found under salt-alkaline conditions. Additionally, the phosphorus translocation significantly decreased in C25 and T315 in the stress treatment. In conclusion, the results indicated that salt-alkaline-tolerant rice genotypes may have stronger abilities to assimilate and transfer biomass and phosphorus than sensitive genotypes, especially in salt-alkaline conditions.