Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control

Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear. The mitochondria-specific peroxidase Peroxiredoxin 3 (Prdx3) plays a protective role against mitochondrial dysfunction by removing mitochondrial reactive oxygen species. Therefore, we investigated whether Prdx3-deficiency directly leads to heart failure via mitochondrial dysfunction. Fifty-two-week-old Prdx3-deficient mice exhibited cardiac hypertrophy and dysfunction with giant and damaged mitochondria. Mitophagy was markedly suppressed in the hearts of Prdx3-deficient mice compared to the findings in wild-type and Pink1-deficient mice despite the increased mitochondrial damage induced by Prdx3 deficiency. Under conditions inducing mitophagy, we identified that the damaged mitochondrial accumulation of PINK1 was completely inhibited by the ablation of Prdx3. We propose that Prdx3 interacts with the N-terminus of PINK1, thereby protecting PINK1 from proteolytic cleavage in damaged mitochondria undergoing mitophagy. Our results provide evidence of a direct association between MQC dysfunction and cardiac function. The dual function of Prdx3 in mitophagy regulation and mitochondrial oxidative stress elimination further clarifies the mechanism of MQC in vivo and thereby provides new insights into developing a therapeutic strategy for mitochondria-related cardiovascular diseases such as heart failure. © 20221

Loss of the Promyelocytic Leukemia Protein in Gastric Cancer: Implications for IP-10 Expression and Tumor-Infiltrating Lymphocytes

Gastric cancer is one of the most common causes of cancer-related mortality worldwide. Expression of the tumor suppressor, promyelocytic leukemia (PML) protein, is reduced or abolished in gastric carcinomas, in association with an increased level of lymphatic invasion, development of higher pTNM staging, and unfavorable prognosis. Herein, we investigated the relationship between the extent of tumor-infiltrating lymphocytes and the status of PML protein expression in advanced gastric carcinoma. We observed higher numbers of infiltrating T-cells in gastric carcinoma tissues in which PML expression was reduced or abolished, compared to tissues positive for PML. The extent of T-cell migration toward culture supernatants obtained from interferon-gamma (IFN-γ-stimulated gastric carcinoma cell lines was additionally affected by expression of PML in vitro. Interferon-gamma-inducible protein 10 (IP-10/CXCL10) expression was increased in gastric carcinoma tissues displaying reduced PML levels. Moreover, both Pml knockout and knockdown cells displayed enhanced IP-10 mRNA and protein expression in the presence of IFN-γ. PML knockdown increased IFN-γ-mediated Signal Transducer and Activator of Transcription-1 (STAT-1) binding to the IP-10 promoter, resulting in elevated transcription of the IP-10 gene. Conversely, PML IV protein expression suppressed IP-10 promoter activation. Based on these results, we propose that loss of PML protein expression in gastric cancer cells contributes to increased IP-10 transcription via enhancement of STAT-1 activity, which, in turn, promotes lymphocyte trafficking within tumor regions

The Conjugated Phenylene Polymer-Modified Photoanodes for Quantum Dot-Sensitized Solar Cells

Five types of conjugated phenylene polymer-modified photoanodes for quantum dot-sensitized solar cells (QDSSCs) were prepared by immobilization of CdSe QDs after electrochemical polymerization of functionalized phenyldiazonium salts onto ITO glass electrodes. The successful preparation of the conjugated phenylene polymer-modified photoanodes for QDSSCs was confirmed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), FT-IR spectroscopy, UV-visible spectroscopy, contact angles, and electrochemical impedance spectroscopy. The open-circuit voltage and fill factor in QDSSCs with the conjugated phenylene polymer with -COOH photoanodes were achieved at 0.52 V and 76.8%, respectively, and the energy conversion efficiency was improved to 2.73% using the conjugated phenylene polymer with -COOH photoanodes

Two-dimensional material-based bionano platforms to control mesenchymal stem cell differentiation

Abstract Background In the past decade, stem cells, with their ability to differentiate into various types of cells, have been proven to be resourceful in regenerative medicine and tissue engineering. Despite the ability to repair damaged parts of organs and tissues, the use of stem cells still entails several limitations, such as low differentiation efficiency and difficulties in guiding differentiation. To address these limitations, nanotechnology approaches have been recently implemented in stem cell research. It has been discovered that stem cells, in combination with carbon-based functional materials, show enhanced regenerative performances in varying biophysical conditions. In particular, several studies have reported solutions to the conventional quandaries in biomedical engineering, using synergetic effects of nanohybrid materials, as well as further development of technologies to recover from diverse health conditions such as bone fracture and strokes. Main text In this review, we discuss several prior studies regarding the application of various nanomaterials in controlling the behavior of stem cells. We focus on the potential of different types of nanomaterials, such as two-dimensional materials, gold nanoparticles, and three-dimensional nanohybrid composites, to control the differentiation of human mesenchymal stem cells (hMSCs). These materials have been found to affect stem cell functions via the adsorption of growth/differentiation factors on the surfaces of nanomaterials and the activation of signaling pathways that are mostly related to cell adhesion and differentiation (e.g., FAK, Smad, Erk, and Wnt). Conclusion Controlling stem cell differentiation using biophysical factors, especially the use of nanohybrid materials to functionalize underlying substrates wherein the cells attach and grow, is a promising strategy to achieve cells of interest in a highly efficient manner. We hope that this review will facilitate the use of other types of newly discovered and/or synthesized nanomaterials (e.g., metal transition dichalcogenides, non-toxic quantum dots, and metal oxide frameworks) for stem cell-based regenerative therapies

Solution Process Engineering for Improving Stability and Efficiency of Perovskite Solar Cells

In recent years, organic-inorganic halide perovskite solar cells (PSCs) have emerged as the fastest growing solar cell technology. This is due to their rapid performance improvement from 3.8% in 2009 to 25.2% most recently due to their outstanding optoelectronic and material properties. For the technology to be commercially viable, practical-size-cells and stable perovskite cells need to be demonstrated. Solution process engineering is one of the most effective methods of engineering the formation of perovskite for high quality film to improve stability and performance devices. The first part of this thesis develops a scalable anti-solvent process for improving perovskite formation, i.e. a spray method using a mixture of chlorobenzene (CBZ) and acetonitrile (ACN). It is found that CBZ is responsible for facilitating perovskite nucleation and ACN as a weak polarity solvent performs two functions i) allows the organic salt in the perovskite complex to be re-dissolved for perovskite formation and ii) loosens the DMSO-PbI2 bond for more rapid perovskite crystallization. The second part of this thesis tackles the moisture instability of perovskite solar cells by using a method of mixing Phenethylammonium (PEA), a hydrophobic cation, with perovskite precursors for the formation of (FAPbI3)0.85(MABr3)0.15. PEA is shown to be effective in passivating the grain boundaries and the TiO2 / perovskite interface, resulting in improved cell stability. The last part of this thesis investigates the impact of the different perovskite precursor preparation methods on perovskite film properties and stability behaviour in PEA-based perovskite solar cells. Two different precursor preparation methods which are termed the (i) “different phase method” (DP) where perovskite precursor is a mixture of 3D (FA0.85MA0.15Pb(I0.85Br0.15)3) + 2D (PEA2Pb(I0.85Br0.15)4) ) and ii) “same phase methods” (SP) where pre-mixed precursors: quasi-2D (PEA2FAn-1PbnI3n+1) + quasi-2D (PEA2MAn-1PbnBr3n+1) are used for film deposition. SP perovskite devices show dramatic improvement in humidity stability due to different perovskite structure from different formation mechanism. The new insights provided by these works highlight the importance of perovskite composition engineering, solvent engineering and precursor preparation methods for improving device performance and stability

Multi-pass cold rolling and wire drawing process of gadolinium and its magnetocaloric effect

Owing to low ductility of magnetocaloric material (MCM)s, the plastic deformation process is quite challenging, and information available on the deformation process of MCMs is limited. In this study, the cold rolling and wire drawing processes of Gd wire including heat treatment were conducted. Uniaxial compression test of as-cast and heat treated Gd rod was conducted to evaluate the material property. The magnetocaloric effect (MCE) of drawn Gd wire was indirectly measured using a vibrating sample magnetometer (VSM). Pass schedule of cold rolling and wire drawing process for the Gd wire of Ø1.0 was designed. Finite element (FE) simulation of drawing process was conducted to investigate the drawing force for each drawing pass and strain distribution. Friction coefficient between the drawing die and Gd wire was evaluated via FE simulation and drawing experiments using a lubricant. Magnetic properties of the deformed and annealed Gd wire were evaluated and compared. The evaluated magnetic properties have shown that the presented process schedule is reasonable for manufacturing magnetocaloric wire without diminishing the magnetocaloric effect

Significant relationship between Arctic warming and East Asia hot summers

Arctic warming is of growing interest because it could affect midlatitude climates. Even though numerous studies have paid attention to the relationship between Arctic warming and the midlatitude climate in winter, the influence of Arctic warming on the summer conditions has not been examined in depth. Here we identify a significant relationship between East Asia hot summers and Arctic warming over the Barents and Kara seas. To represent Arctic warming, we define a combined index by simply differencing the normalized surface air temperature and sea-ice indices. We found that the combined index in July has significantly high correlations with the temperatures in China, Korea, and Japan. While the teleconnection mechanism is not completely revealed, it is evident that warming over the Barents and Kara seas is accompanied by the local development of an anomalous anticyclone and downstream wave trains, which yield a strong anticyclonic circulation over East Asia and the North Pacific. The anticyclonic circulation persists and intensifies until August, which leads to hot summer conditions in East Asia with warm advection and enhanced shortwave radiation. Our results suggest that Arctic climate conditions can be used as a useful precursor of East Asia temperature variations even in summer

Control over Alignment and Growth Kinetics of Si Nanowires through Surface Fluctuation of Liquid Precursor

Control over alignment and growth kinetics of vertically aligned Si nanowire (<i>v</i>-SiNW) arrays, which were grown using chemical vapor deposition (CVD) via a metal catalyst-assisted vapor–liquid–solid (VLS) mechanism, was demonstrated by introducing a homemade bubbler system containing a SiCl₄ solution as the Si precursor. Careful control over the bubbler afforded different amounts of SiCl₄ supplied to the reactor. By varying the dipping depth (<i>D</i>_d) and tilting angle (<i>T</i>_a) of the bubbler, the SiCl₄ precursor concentration would fluctuate to different degrees. The different SiCl₄ concentrations afforded the fine-tuning of <i>v</i>-SiNW array properties like alignment and growth kinetics. The degree of alignment of <i>v</i>-SiNWs could be increased with large amounts of SiCl₄, which was caused by slight shallow depth or gentle tilting of the SiCl₄ solution in the bubbler due to an increasing degree of fluctuation and fluctuation area. The ability to control alignment and growth kinetics of <i>v</i>-SiNW arrays could be employed in advanced nanoelectronic devices

Correlation between <i>PPARG</i> Pro12Ala Polymorphism and Therapeutic Responses to Thiazolidinediones in Patients with Type 2 Diabetes: A Meta-Analysis

Background: Thiazolidinediones (TZDs) are a type of oral drug that are utilized for the treatment of type 2 diabetes mellitus (T2DM). They function by acting as agonists for a nuclear transcription factor known as peroxisome proliferator-activated receptor-gamma (PPAR-γ). TZDs, such as pioglitazone and rosiglitazone, help enhance the regulation of metabolism in individuals with T2DM by improving their sensitivity to insulin. Previous studies have suggested a relationship between the therapeutic efficacy of TZDs and the PPARG Pro12Ala polymorphism (C > G, rs1801282). However, the small sample sizes of these studies may limit their applicability in clinical settings. To address this limitation, we conducted a meta-analysis assessing the influence of the PPARG Pro12Ala polymorphism on the responsiveness of TZDs. Method: We registered our study protocol with PROSPERO, number CRD42022354577. We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases, including studies published up to August 2022. We examined studies investigating the association between the PPARG Pro12Ala polymorphism and metabolic parameters such as hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). The mean difference (MD) and 95% confidence intervals (CIs) between pre- and post-drug administration were evaluated. The quality of the studies included in the meta-analysis was assessed by using the Newcastle–Ottawa Scale (NOS) tool for cohort studies. Heterogeneity across studies was assessed by using the I2 value. An I2 value greater than 50% indicated substantial heterogeneity, and a random-effects model was used for meta-analysis. If the I2 value was below 50%, a fixed-effects model was employed instead. Both Begg’s rank correlation test and Egger’s regression test were performed to detect publication bias, using R Studio software. Results: Our meta-analysis incorporated 6 studies with 777 patients for blood glucose levels and 5 studies with 747 patients for lipid levels. The included studies were published between 2003 and 2016, with the majority involving Asian populations. Five of the six studies utilized pioglitazone, while the remaining study employed rosiglitazone. The quality scores, as assessed with the NOS, ranged from 8 to 9. Patients carrying the G allele exhibited a significantly greater reduction in HbA1C (MD = −0.3; 95% CI = −0.55 to −0.05; p = 0.02) and FPG (MD = −10.91; 95% CI = −19.82 to −2.01; p = 0.02) levels compared to those with the CC genotype. Furthermore, individuals with the G allele experienced a significantly larger decrease in TG levels than those with the CC genotype (MD = −26.88; 95% CI = −41.30 to −12.46; p = 0.0003). No statistically significant differences were observed in LDL (MD = 6.69; 95% CI = −0.90 to 14.29; p = 0.08), HDL (MD = 0.31; 95% CI = −1.62 to 2.23; p = 0.75), and TC (MD = 6.4; 95% CI = −0.05 to 12.84; p = 0.05) levels. No evidence of publication bias was detected based on Begg’s test and Egger’s test results. Conclusions: This meta-analysis reveals that patients with the Ala12 variant in the PPARG Pro12Ala polymorphism are more likely to exhibit positive responses to TZD treatment in terms of HbA1C, FPG, and TG levels compared to those with the Pro12/Pro12 genotype. These findings suggest that genotyping the PPARG Pro12Ala in diabetic patients may be advantageous for devising personalized treatment strategies, particularly for identifying individuals who are likely to respond favorably to TZDs

Development of stimuli-responsive flexible micropillar composites via magneto-induced injection molding and characterization of magnetic particle alignment

Magnetic soft composites have emerged as a promising soft actuator with a high degree of precision in the magnetic field stimuli system. But, their mass manufacturing strategies have yet to be developed, and most studies focus on small-scale near-net shaping production. Here, we first apply injection molding (which only takes a few seconds to shape) to fabricate the stimuli-responsive flexible micropillar composites with magnetic particle alignment design using an external magnetic field. The arrays exhibit magnetically anisotropic particle alignment up to 82.57 % along the longitudinal direction, showing a magnetic bending actuation response. We achieve a structural novelty of the magnetic micropillar with a high aspect ratio of up to 10 and pattern sizes of 50 μm via sacrificial LIGA insert mold and magneto-induced injection molding. For advanced mass production, the permanent metal mold is also applied to develop the micropillar composites based on the mechanical demolding approach; successful manufacturing is achieved by fabricating defect-free micropillar with 200 μm cylindrical pattern size and aspect ratio of 6. Further, the effect of powder volume fraction on the magneto-rheological behavior and corresponding magnetic performance is characterized in the injection molding process. The magnetic particle alignment trend is confirmed by the torque balance and the criteria of critical solids loading. Finally, we establish an injection molding process for magnetic soft composites, and verify the optimal powder fraction for the particle alignment