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Abstract Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.

Abstract Background Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. Methods Western blotting, quantitative real‐time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan–Meier curves were employed for survival analysis. CCK‐8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA‐sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP‐GFP‐LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2‐interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. Results The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki‐67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy‐related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. Conclusions These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

Abstract In recent years, countries worldwide have engaged actively in the research and development of green and sustainable materials in the face of the increasing depletion of petroleum resources, the need to reduce material waste, and the environmental pollution caused by the various types of waste. In the tire industry, the key materials for the various components of tires are mostly dependent on petroleum resources. Development of green tires and green processing technologies using sustainable materials is an important development direction for the future of the tire industry, and many tire‐manufacturing companies have proposed their visions for the development of eco‐friendly tires. Rubber, cord fabric, and additives are the main materials used in tire manufacturing. This article summarizes the research status of the green materials that can meet the requirements of environmental friendliness and sustainability, replace traditional materials, and reduce petroleum resource consumption in existing tire production. These materials mainly include natural rubber or bio‐based synthetic rubber, green renewable cord fabrics, and green processing additives. The prospects for the application of these new green materials in tire manufacturing are also discussed.

Abstract Background Mastitis is one of the most severe diseases in humans and animals, especially on dairy farms. Mounting evidence indicates that gastrointestinal dysbiosis caused by induction of subacute ruminal acidosis (SARA) by high-grain diet consumption and low in dietary fiber is associated with mastitis initiation and development, however, the underlying mechanism remains unknown. Results In the present study, we found that cows with SARA-associated mastitis have altered metabolic profiles in the rumen, with increased sialic acids level in particular. Consumption of sialic acid (SA) in antibiotic-treated mice, but not healthy mice, induced marked mastitis. SA treatment of antibiotic-treated mice also induced mucosal and systemic inflammatory responses, as evidenced by increased colon and liver injuries and several inflammatory markers. In addition, gut dysbiosis caused by antibiotic impaired gut barrier integrity, which was aggravated by SA treatment. SA potentiated serum LPS level caused by antibiotic treatment, leading to increased activation of the TLR4-NF-κB/NLRP3 pathways in the mammary gland and colon. Moreover, SA facilitated gut dysbiosis caused by antibiotic, and especially enhanced Enterobacteriaceae and Akkermansiaceae, which correlated with mastitis parameters. Fecal microbiota transplantation from SA-antibiotic-treated mice mimicked mastitis in recipient mice. In vitro experiments showed that SA prompted Escherichia coli growth and virulence gene expression, leading to higher proinflammatory cytokine production in macrophages. Targeting the inhibition of Enterobacteriaceae by sodium tungstate or treating with the commensal Lactobacillus reuteri alleviated SA-facilitated mastitis. In addition, SARA cows had distinct ruminal microbial structure by the enrichment of SA-utilizing opportunistic pathogenic Moraxellaceae and the depletion of SA-utilizing commensal Prevotellaceae. Treating mice with the specific sialidase inhibitor zanamivir reduced SA production and Moraxellaceae abundance, and improved mastitis in mice caused by ruminal microbiota transplantation from cows with SARA-associated mastitis. Conclusions This study, for the first time, indicates that SA aggravates gut dysbiosis-induced mastitis by promoting gut microbiota disturbance and is regulated by commensal bacteria, indicating the important role of the microbiota-gut-mammary axis in mastitis pathogenesis and suggesting a potential strategy for mastitis intervention based on gut metabolism regulation. Video Abstract

Subacute ruminal acidosis (SARA) has been demonstrated to promote the development of mastitis, one of the most serious diseases in dairy farming worldwide, but the underlying mechanism is unclear. Using untargeted metabolomics, we found hexadecanamide (HEX) was significantly reduced in rumen fluid and milk from cows with SARA-associated mastitis. Herein, we aimed to assess the protective role of HEX in Staphylococcus aureus (S. aureus)- and SARA-induced mastitis and the underlying mechanism. We showed that HEX ameliorated S. aureus-induced mastitis in mice, which was related to the suppression of mammary inflammatory responses and repair of the blood-milk barrier. In vitro, HEX depressed S. aureus-induced activation of the NF-κB pathway and improved barrier integrity in mouse mammary epithelial cells (MMECs). In detail, HEX activated PPARα, which upregulated SIRT1 and subsequently inhibited NF-κB activation and inflammatory responses. In addition, ruminal microbiota transplantation from SARA cows (S-RMT) caused mastitis and aggravated S. aureus-induced mastitis, while these changes were reversed by HEX. Our findings indicate that HEX effectively attenuates S. aureus- and SARA-induced mastitis by limiting inflammation and repairing barrier integrity, ultimately highlighting the important role of host or microbiota metabolism in the pathogenesis of mastitis and providing a potential strategy for mastitis prevention.

Understanding the two-phase displacement behaviors of oil and water in porous media under different reservoir development modes for enhanced oil recovery is essential. In this paper, the influence of development measures, such as increasing the injection rate, changing the inlet/outlet position, increasing the water viscosity, and reducing the surface tension coefficient, on oil–water dynamic behaviors was studied using a numerical simulation based on the study of the formation of a high-water-cut channel by water flooding at different injection rates. The results show that blockage and restart occur during displacement in the pore–throat channel and during staggered displacement in different pore channels. With an increase in the injection rate, the recovery increases first and then decreases. All the different development measures can increase the swept area and recovery factor. The recovery factor increases significantly by reducing the surface tension coefficient at medium/high injection rates (≥0.01 m/s) and by increasing the viscosity of the water at low injection rates (

ABSTRACT Intestinal microbiota-mediated aryl hydrocarbon receptor (AhR) activation plays an important role in host–microbiota interactions and disease development. However, whether AhR activation mediates infection-induced inflammation in remote organs is not clear. The purpose of this study is to assess the effects and underlying mechanism of AhR activation and gut microbiota-mediated dietary tryptophan (Trp) metabolism on infection-induced inflammation using an Escherichia coli (E. coli)-induced endometritis model in mice. We found that AhR activation by 6-formylindolo (3,2-b) carbazole (Ficz), which is an AhR agonist derived from the photooxidation of Trp, alleviated E. coli-induced endometritis by repairing barrier function and inhibiting inflammatory responses, while inhibition of AhR by CH223191, which is a synthetic AhR antagonist, aggravated E. coli-induced endometritis. Gut dysbiosis damaged AhR activation and exacerbated E. coli-induced endometritis in mice, which responded to the reduced abundance of AhR ligand producers, such as Lactobacillus spp. Supplementation with dietary Trp ameliorated E. coli-induced endometritis in a microbiota-dependent manner, which was associated with the production of AhR ligands. Administration of AhR ligands, including indole and indole aldehyde, but not indole-3-propionic acid, rescued the protective effect of Trp on E. coli-induced endometritis in dysbiotic mice. Moreover, consumption of Lactobacillus reuteri (L. reuteri) containing AhR ligand-producing capability also alleviated E. coli-induced endometritis in mice in an AhR-dependent manner. Our results demonstrate that microbiota-mediated AhR activation is a key factor in fighting pathogen-caused inflammation, which leads to a potential strategy to regulate the gut microbiota and metabolism by dietary Trp or probiotics for the intervention of infectious diseases and reproductive health. IMPORTANCE Infection-induced endometritis is a common and frequently occurring disease in humans and animals. Accumulating evidence suggests an important role of the gut microbiota in the development of infection-induced inflammation. Whether and how gut microbiota-mediated AhR activation regulates the pathogenesis of pathogen-induced endometritis remains unknown. The current study found that AhR activation ameliorated E. coli-induced endometritis, and inhibition of AhR produced negative results. Gut dysbiosis reduced the abundance of AhR ligand producers including Lactobacillus spp., damaged AhR activation, and exacerbated E. coli-induced endometritis. Supplementation with dietary Trp, AhR ligands, and L. reuteri containing AhR ligand-producing capability alleviated E. coli-induced endometritis in mice. Our results suggest an important role of microbiota-mediated AhR activation in the pathogenesis of endometritis and provide potential strategies for the intervention of infectious diseases and reproductive health by regulating the gut microbiota and metabolism.

Abstract Background Inosine 5′-monophosphate dehydrogenase type II (IMPDH2) was originally identified as an oncogene in several human cancers. However, the clinical significance and biological role of IMPDH2 remain poorly understood in colorectal cancer (CRC). Methods Quantitative real-time polymerase chain reaction (qPCR), western blotting analysis, the Cancer Genome Atlas (TCGA) data mining and immunohistochemistry were employed to examine IMPDH2 expression in CRC cell lines and tissues. A series of in-vivo and in-vitro assays were performed to demonstrate the function of IMPDH2 and its possible mechanisms in CRC. Results IMPDH2 was upregulated in CRC cells and tissues at both mRNA and protein level. High IMPDH2 expression was closely associated with T stage, lymph node state, distant metastasis, lymphovascular invasion and clinical stage, and significantly correlated with poor survival of CRC patients. Further study revealed that overexpression of IMPDH2 significantly promoted the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells in vitro and accelerated xenograft tumour growth in nude mice. On the contrary, knockdown of IMPDH2 achieved the opposite effect. Gene set enrichment analysis (GSEA) showed that the gene set related to cell cycle was linked to upregulation of IMPDH2 expression. Our study verified that overexpressing IMPDH2 could promote G1/S phase cell cycle transition through activation of PI3K/AKT/mTOR and PI3K/AKT/FOXO1 pathways and facilitate cell invasion, migration and EMT by regulating PI3K/AKT/mTOR pathway. Conclusions These results suggest that IMPDH2 plays an important role in the development and progression of human CRC and may serve as a novel prognostic biomarker and therapeutic target for CRC.

In recent years, the development of deep learning-based remaining useful life (RUL) prediction methods of bearings has flourished because of their high accuracy, easy implementation, and lack of reliance on a priori knowledge. However, there are two challenging issues concerning the prediction accuracy of existing methods. The run-to-failure sequential data and its RUL labels are almost inaccessible in real-world scenarios. Meanwhile, the existing models usually capture the general degradation trend of bearings while ignoring the local information, which restricts the model performance. To tackle the aforementioned problems, we propose a novel health indicator derived from the original vibration signals by combining principal components analysis with Euclidean distance metric, which was motivated by the desire to resolve the dependency on RUL labels. Then, we design a novel self-attention augmented convolution GRU network (SACGNet) to predict the RUL. Combining a self-attention mechanism with a convolution framework can both adaptively assign greater weights to more important information and focus on local information. Furthermore, Gated Recurrent Units are used to parse the long-term dependencies in weighted features such that SACGNet can utilize the important weighted features and focus on local features to improve the prognostic accuracy. The experimental results on the PHM 2012 Challenge dataset and the XJTU-SY bearing dataset have demonstrated that our proposed method is superior to the state of the art.

Abstract Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P

In supervised learning, obtaining a large set of fully-labeled training data is expensive. We show that we do not always need full label information on every single training example to train a competent classifier. Specifically, inspired by the principle of sufficiency in statistics, we present a statistic (a summary) of the fully-labeled training set that captures almost all the relevant information for classification but at the same time is easier to obtain directly. We call this statistic "sufficiently-labeled data" and prove its sufficiency and efficiency for finding the optimal hidden representations, on which competent classifier heads can be trained using as few as a single randomly-chosen fully-labeled example per class. Sufficiently-labeled data can be obtained from annotators directly without collecting the fully-labeled data first. And we prove that it is easier to directly obtain sufficiently-labeled data than obtaining fully-labeled data. Furthermore, sufficiently-labeled data is naturally more secure since it stores relative, instead of absolute, information. Extensive experimental results are provided to support our theory. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) have been demonstrated to serve important roles in the development and progression of cancer. Recently HNF1A antisense RNA 1 (HNF1A‑AS1), a lncRNA, has been reported as exhibiting a potential oncogenic role in the development of many types of cancer. However, the expression and the role of HNF1A‑AS1 in colorectal carcinoma (CRC) remains unclear. In the present study, the role of HNF1A‑AS1 in CRC was examined for the first time and its correlation with CRC cell biological behaviors was analyzed. The results demonstrated that HNF1A‑AS1 was distinctly upregulated in CRC tissues and associated with CRC metastasis to the lymph nodes. Reverse transcription‑quantitative polymerase chain reaction revealed that HNF1A‑AS1 was also upregulated in CRC cell lines and localized in the nucleus. In addition, knockdown of HNF1A‑AS1 expression notably inhibited CRC cell proliferation, migration, invasion and colony formation, and suppressed S‑phase entry in vitro. Taken together, these results suggested that HNF1A‑AS1 might serve as a promising prognostic marker for CRC tumorigenesis and progression. [ABSTRACT FROM AUTHOR]

Glycosidase is an indispensable enzyme in the sugar industry. It is difficult to maintain the stability of natural glycosidase during long-term high-temperature sugar conversion, limiting its application in industrial production. Numerous studies have shown that protein engineering is an important means for enhancing the thermal stability of glycosidase. This article systematically reviews the latest advances in using protein engineering to improve the thermal stability of glycosidase, and dissects the directed evolution, rational design, and semi-rational design strategies used in protein engineering. It also evaluates the effectiveness of these strategies in enhancing the thermal stability of glycosidase and their potential industrial application value, and presents the advantages, limitations and challenges of each strategy. Finally, it suggests that different strategies should be jointly used to improve the thermal stability of glycosidase and gives an outlook on future research directions with a view to promoting the synergistic improvement of the thermal stability and activity of glycosidase.