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Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.

Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.

Decentralized water treatment technologies, designed to align with the specific characteristics of the water source and the requirements of the user, are gaining prominence due to their cost and energy-saving advantages over traditional centralized systems. The application of chemical water treatment via heterogeneous advanced oxidation processes using peroxide (O–O) represents a potentially attractive treatment option. These processes serve to initiate redox processes at the solid-water interface. Nevertheless, the oxidation mechanism exemplified by the typical Fenton-like persulfate-based heterogeneous oxidation, in which electron transfer dominates, is almost universally accepted. Here, we present experimental results that challenge this view. At the solid-liquid interface, it is demonstrated that protons are thermodynamically coupled to electrons. In situ quantitative titration provides direct experimental evidence that the coupling ratio of protons to transferred electrons is almost 1:1. Comprehensive thermodynamic analyses further demonstrate that a net proton-coupled electron transfer occurs, with both protons and electrons entering the redox cycle. These findings will inform future developments in O–O activation technologies, enabling more efficient redox activity via the tight coupling of protons and electrons. Chemical water treatment through heterogeneous advanced oxidation offers promise for decentralized applications. Here, authors challenge the conventional electron-transfer mechanism of O–O activation, demonstrating that at solid-water interfaces, the process involves coupled proton-electron transfer rather than pure electron transport.

Silicon (Si) plays important roles in alleviating heavy metal stress in rice plants. Here we investigated the physiological response of rice at different growth stages under the silicon-induced mitigation of cadmium (Cd) and zinc (Zn) toxicity. Si treatment increased the dry weight of shoots and roots and reduced the Cd and Zn concentrations in roots, stems, leaves and grains. Under the stress of exposure to Cd and Zn, photosynthetic parameters including the chlorophyll content and chlorophyll fluorescence decreased, while the membrane permeability and malondialdehyde (MDA) increased. Catalase (CAT) and peroxidase (POD) activities increased under heavy metals stress, but superoxide dismutase (SOD) activities decreased. The magnitude of these Cd- and Zn-induced changes was mitigated by Si-addition at different growth stages. The available Cd concentration increased in the soil but significantly decreased in the shoots, which suggested that Si treatment prevents Cd accumulation through internal mechanisms by limiting Cd2+ uptake by the roots. Overall, the phenomena of Si-mediated alleviation of Cd and excess Zn toxicity in two rice cultivars could be due to the limitation of metal uptake and transport, resulting in an improvement in cell membrane integrity, photosynthetic performance and anti-oxidative enzyme activities after Si treatment.

Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined. The core set of genes relating to histone methylation ( KMT2D , KMT2C , EZH2 ), histone acetylation ( CREBBP , EP300 ), DNA methylation ( TET2 ), and chromatin remodeling ( ARID1A ) were detected in the training cohort of 316 patients by whole-genome/exome sequencing (WGS/WES) and in the validation cohort of 303 patients with newly diagnosed DLBCL by targeted sequencing. Their correlation with peripheral blood immune cells and clinical outcomes were assessed. Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo. Among all 619 DLBCL patients, somatic mutations in KMT2D (19.5%) were most frequently observed, followed by mutations in ARID1A (8.7%), CREBBP (8.4%), KMT2C (8.2%), TET2 (7.8%), EP300 (6.8%), and EZH2 (2.9%). Among them, CREBBP / EP300 mutations were significantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios, as well as inferior progression-free and overall survival. In B-lymphoma cells, the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation, downregulated FBXW7 expression, activated the NOTCH pathway, and downstream CCL2/CSF1 expression, resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation. In B-lymphoma murine models, xenografted tumors bearing CREBBP / EP300 mutation presented lower H3K27 acetylation, higher M2 macrophage recruitment, and more rapid tumor growth than those with CREBBP / EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.

Sodium-glucose co-transport protein 2 (SGLT2) inhibitors, a novel category of oral hypoglycemic agents, offer a promising outlook for individuals experiencing heart failure with reduced ejection fraction. Evidence is emerging that highlights their potential in alleviating myocardial fibrosis and oxidative stress. However, the precise mechanisms through which SGLT2 inhibitors influence myocardial fibrosis induced by angiotensin II (Ang II) or transforming growth factor-β1 (TGF-β1) are not fully understood. This study aims to explore the intricate mechanisms by which SGLT2 inhibitors ameliorate myocardial fibrosis, particularly focusing on the nuanced interplay within the SIRT6 signaling pathway. Primary cardiac fibroblasts were isolated from the hearts of 1-3-day-old neonatal KM mice, were stimulated with Ang II or TGF-β1 to establish an in vitro model of myocardial fibrosis. Treatment with 10 µM Empagliflozin (EMPA) and Dapagliflozin (DAPA) significantly curtailed the proliferation of cardiac fibroblasts, substantially reduced collagen expression induced by Ang II/TGF-β1, and mitigated the phenotypic transformation and oxidative stress response. SIRT6, which is closely associated with myocardial fibrosis, demonstrated that the suppression its expression attenuated the protective effects of EMPA and DAPA against myocardial fibrosis and oxidative stress. Our findings suggest that SGLT2 inhibitors markedly decrease the Ang II/TGF-β1-induced transformation of cardiac fibroblasts to a myofibroblast phenotype by upregulating SIRT6 protein expression, thereby inhibiting oxidative stress and ameliorating myocardial fibrosis.

Advanced thermal management is significant for flat-plate solar collectors, microelectronic cooling devices, thin-film drying units, and advanced heat exchangers. For a solar collector, its physical model can be described as a hybrid nanofluid heat transfer over a planar surface under magnetic field and solar thermal radiation, which has not been studied before. By combining Response Surface Methodology (RSM) and Artificial Neural Network (ANN), we present a model with a comprehensive analysis of a three-dimensional laminar thin-film water-based Cu-Al 2 O 3 hybrid nanofluid over an inclined rotating planar surface under the impacts of gravitational field, magnetic field, and incident solar radiation using thermal convective boundary condition. The sensitivity of the key factors influencing the thermal performance of the nanosystem is recognized and ranked by RSM. Results reveal that the thermal Biot number is the supreme critical factor affecting the heat transfer rate, followed in order by irradiance and absorption factors. In addition, the reliability of the RSM model is validated by the error analysis, which demonstrates an excellent agreement between the results obtained by RSM and numerically computed (obtained via collocation method); moreover, both results well match the experimental runs. Based on the numerical data, an Artificial Neural Network (ANN) model is also developed to predict thermal performance. Results demonstrate an outstanding predictive accuracy of the ANN model with minimal mean squared (relative) error of 1.386 × 10 −8 and near-perfect regression value of 99.99%. Overall, this analysis highlights the successful applications of numerical simulation, RSM-based sensitivity analysis and ANN-based predictive modelling for analysing hybrid nanofluid flow and heat transfer in thin film configurations. Significant technical insights provided by this research will benefit the design of thermal systems requiring advanced thermal management.

Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production. Lipophagy is the degradation of lipid droplets by the autophagy machinery. Here, the authors identify that autophagy protein ATG14 also targets lipid droplets and interacts with ATG8 proteins, functioning as an autophagic receptor for STX18-regulated lipophagy.

Previous studies on topology optimization subject to stress constraints usually considered von Mises or Drucker–Prager criterion. In some engineering applications, e.g., the design of concrete structures, the maximum first principal stress (FPS) must be controlled in order to prevent concrete from cracking under tensile stress. This paper presents an effective approach to dealing with this issue. The approach is integrated with the bi-directional evolutionary structural optimization (BESO) technique. The p -norm function is adopted to relax the local stress constraint into a global one. Numerical examples of compliance minimization problems are used to demonstrate the effectiveness of the proposed algorithm. The results show that the optimized design obtained by the method has slightly higher compliance but significantly lower stress level than the solution without considering the FPS constraint. The present methodology will be useful for designing concrete structures.

The change in phenols, polysaccharides and volatile profiles of noni juice from laboratory- and factory-scale fermentation was analyzed during a 63-day fermentation process. The phenol and polysaccharide contents and aroma characteristics clearly changed according to fermentation scale and time conditions. The flavonoid content in noni juice gradually increased with fermentation. Seventy-three volatile compounds were identified by solid-phase microextraction coupled with gas chromatography–mass spectrometry (SPME-GC-MS). Methyl hexanoate, 3-methyl-3-buten-1-ol, octanoic acid, hexanoic acid and 2-heptanone were found to be the main aroma components of fresh and fermented noni juice. A decrease in octanoic acid and hexanoic acid contents resulted in the less pungent aroma in noni juice from factory-scale fermentation. The results of principal component analysis of the electronic nose suggested that the difference in nitrogen oxide, alkanes, alcohols, and aromatic and sulfur compounds, contributed to the discrimination of noni juice from different fermentation times and scales.