Glycogen synthase kinase-3β (GSK-3β) is an evolutionarily conserved serine/threonine kinase, functioning in numerous cellular processes including cell proliferation, DNA repair, cell cycle, signaling ...and metabolic pathways. GSK-3β is implicated in different diseases including inflammation, neurodegenerative disease, diabetes and cancers. GSK-3β is involved in biological processes of tumorigenesis, therefore, it is rational that GSK-3β inhibitors were employed to target malignant tumors. The effects of GSK-3β inhibitors in combination of radiation and chemotherapeutic drugs have been reported in various types of cancers, suggesting GSK-3β would play important roles in cancer treatments. GSK-3β is involved in multiple signal pathway including Wnt/β-catenin, PI3K/PTEN/AKT and Notch. GSK-3β also functions in DNA repair through phosphorylation of DNA repair factors and affecting their binding to chromatin. This review focuses on the molecular mechanism of GSK-3β in DNA repair, special in base excision repair and double-strands break repair, the roles of GSK-3β in inhibition of apoptosis through activation of NF-κB, and the effects of GSK-3β inhibitors on radio- and chemosensitization of various types of cancers.
This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.
•GSK-3β promotes DNA repair, base excision repair and double strands break repair.•GSK-3β inhibits apoptosis through activation of NF-κB signals.•GSK-3β sensitizes cancer cells to chemotherapy and radiotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The integration of various omics information—such as DNA, RNA, protein, and epigenetic regulation—brings new opportunities for the mining of important economic traits of animals and the analysis of ...molecular genetic mechanisms. Over the last three decades, world milk production has increased by more than 59%, from 530 million tonnes to 843 million tonnes. However, the genetic mechanisms behind milk fat traits remain largely undetermined. Milk is rich in fatty acids, proteins, and eight essential amino acids needed by the human body. The fatty acids in milk, namely, dodecylic acid, myristic acid, stearic acid, and palmitic acid, are the main energy substances in the human body, accounting for approximately 5, 10, 8, and 27 % of total fatty acids, respectively. Thus, decoding the genetics of milk fat traits can have a potential impact on product development, international trade, and consumption of milk components. This Special Issue focuses on applying the aforementioned advances to explore gene regulation and its molecular mechanisms in milk fat traits. The topics include but are not limited to: Research and application surrounding the genetic basis of important milk fat traits; Mining and function of excellent genetic resources for milk fat traits; Genetics of nutrition metabolism regulation and efficient production of milk fat; Epigenetic research on genes implicated in milk fat traits; High-throughput sequencing research surrounding genetics of milk fat traits; Construction of gene (including circRNA, lincRNA, miRNA, and mRNA) expression regulatory network maps.
Background
Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics.
Method
This ...multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal–Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD.
Results
Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio OR = 0.512,
P
= 0.0416), lifetime hospitalization history due to BD (OR = 0.516,
P
= 0.0476), and ECT treatment within the past 12 months (OR = 0.293,
P
= 0.0472).
Conclusion
This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD.
Trial Registration Number
Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.
The exploring of catalysts with high‐efficiency and low‐cost for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is one of the key issues for many renewable energy systems ...including fuel cells, metal–air batteries, and water splitting. Despite several decades pursuing, bifunctional oxygen catalysts with high catalytic performance at low‐cost, especially the one that could be easily scaled up for mass production are still missing and highly desired. Herein, a hybrid catalyst with NiCo alloy nanoparticles decorated on N‐doped carbon nanofibers is synthesized by a facile electrospinning method and postcalcination treatment. The hybrid catalyst NiCo@N‐C 2 exhibits outstanding ORR and OER catalytic performances, which is even surprisingly superior to the commercial Pt/C and RuO2 catalysts, respectively. The synergetic effects between alloy nanoparticles and the N‐doped carbon fiber are considered as the main contributions for the excellent catalytic activities, which include decreasing the intrinsic and charge transfer resistances, increasing CC, graphitic‐N/pyridinic‐N contents in the hybrid catalyst. This work opens up a new way to fabricate high‐efficient, low‐cost oxygen catalysts with high production.
NiCo alloy nanoparticles decorated on N‐doped carbon nanofibers as a highly active and durable oxygen electrocatalyst at low‐cost are synthesized and reported. The hybrid catalyst with suitable amount of NiCo alloy nanoparticles loading (NiCo@N‐C 2) gives the most outstanding oxygen reduction reaction and oxygen evolution reaction electrocatalytic performances, which is even surprisingly superior to the commercial Pt/C and RuO2 catalysts, respectively.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism ...QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3β (GSK3β)/GSK3β. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H2O2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H2O2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3β/GSK3β. Meanwhile, it further ameliorated mitochondrion-related apoptosis by inhibiting the mitochondrial fission, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) decline in H9c2 cardiomyocytes induced by H2O2. In addition, all the effects of QLQX on H2O2-induced mitochondria-dependent apoptosis could be blocked by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. We conclude that QLQX may ameliorate oxidative stress-induced mitochondria-dependent apoptosis in cardiomyocytes through PI3K/AKT/GSK3β signaling pathway.
The C3‐alkenyl‐substituted 2‐indolylmethanols have been designed as a new class of substrates for catalytic asymmetric interrupted Nazarov‐type cyclizations. In the presence of chiral phosphoric acid ...as a mild chiral Brønsted acid, the interrupted Nazarov‐type cyclization of C3‐alkenyl‐substituted 2‐indolylmethanols with nucleophiles occurred smoothly to construct cyclopentabindole frameworks in generally excellent diastereo‐ and enantioselectivities (up to >95:5 dr, >99% ee).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell ...types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP‐2 and MMP‐9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0/G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial‐mesenchymal transition (EMT) change with downregulation of E‐cadherin and upregulation of N‐cadherin, Vimentin, α‐SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell‐like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.
We have demonstrated that fusion hybrids between lung cancer cells and MSCs offer enhanced metastatic abilities and cancer stem cell‐like properties by inducing epithelial‐mesenchymal transition (EMT). Our findings suggested that stem cell fusion would provide a new explanation for the origin of cancer stem cells and has an important consequence on lung cancer therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Self‐organized stimuli‐responsive smart materials with adjustable attributes are highly desirable for a plethora of device applications. Simple cubic lattice is quite uncommon in soft condensed ...matter due to its lower packing factor. Achieving a stable simple cubic soft lattice and endowing such a lattice with dynamic reconstruction capability solely by a facile light irradiation are of paramount significance for both fundamental studies and engineering explorations. Herein, an elegant stable self‐organized simple cubic soft lattice, i.e., blue phase II, in a chiral liquid crystal (LC) system is disclosed, which is stable down to room temperature and exhibits both reversible lattice deformation and transformation to a helical superstructure, i.e., cholesteric LC, by light stimulation. Such an amazing trait is attained by doping a judiciously designed achiral photoresponsive molecular switch functionalized polyhedral oligomeric silsesquioxane nanocage into a chiral LC host. An unprecedented reversible collapse and reconstruction of such a high symmetric simple cubic blue phase II driven by light has been achieved. Furthermore, a well‐defined conglomerate micropattern composed of simple cubic soft lattice and helical superstructure, which is challenging to fabricate in organic and inorganic crystalline materials, is produced using photomasking technology. Moreover, the promising photonic application based on such a micropattern is demonstrated.
A reversible and dynamic transformation between a stable simple cubic lattice and a helical superstructure is achieved via light irradiation in a photoresponsive blue phase liquid crystal enabled by a molecular‐switch‐functionalized nanocage. Leveraging this capability, unprecedented light‐driven recording, erasing, and rewriting of well‐defined biphasic micropatterns are demonstrated and photonic applications of such micropatterns are explored.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Engineered cementitious composites (ECCs) are characterized by multiple cracking behaviors, high tensile-strain capacity, and excellent crack-control ability. Representative fine cracks are difficult ...to identify with available methods. This study presents a highly accurate and automatic semantic segmentation method for multiple cracks in ECCs using a dual pre-modification deep-learning strategy that considers its specific task scenario. The proposed strategy significantly improved the MIoU to 98.82 % and class accuracy of cracks from 92.28 % to 99.87 %. The generalizability of the model was verified by applying the method to images that were completely unrelated to the close-set. Overall, the proposed method has no requirements on the size of input images, and the entire processing is completely automatic and takes <5 s for a 4016 × 6016 image. Therefore, the proposed method is more intuitive than the traditional digital image correlation method, and the achieved results are also more informative and accurate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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