Proteasome resides in and dismantles plant heat stress granules constitutively.

Stress granules (SGs) are conserved reversible cytoplasmic condensates enriched with aggregation-prone proteins assembled in response to various stresses. How plants regulate SG dynamics is unclear. Here, we show that 26S proteasome is a stable component of SGs, promoting the overall clearance of SGs without affecting the molecular mobility of SG components. Increase in either temperature or duration of heat stress reduces the molecular mobility of SG marker proteins and suppresses SG clearance. Heat stress induces dramatic ubiquitylation of SG components and enhances the activities of SG-resident proteasomes, allowing the degradation of SG components even during the assembly phase. Their proteolytic activities enable the timely disassembly of SGs and secure the survival of plant cells during the recovery from heat stress. Therefore, our findings identify the cellular process that de-couples macroscopic dynamics of SGs from the molecular dynamics of its constituents and highlights the significance of the proteasomes in SG disassembly.

Three-nucleotide periodicity of nucleotide diversity in a population enables the identification of open reading frames.

Accurate prediction of open reading frames (ORFs) is important for studying and using genome sequences. Ribosomes move along mRNA strands with a step of three nucleotides and datasets carrying this information can be used to predict ORFs. The ribosome-protected footprints (RPFs) feature a significant 3-nt periodicity on mRNAs and are powerful in predicting translating ORFs, including small ORFs (sORFs), but the application of RPFs is limited because they are too short to be accurately mapped in complex genomes. In this study, we found a significant 3-nt periodicity in the datasets of populational genomic variants in coding sequences, in which the nucleotide diversity increases every three nucleotides. We suggest that this feature can be used to predict ORFs and develop the Python package 'OrfPP', which recovers ~83% of the annotated ORFs in the tested genomes on average, independent of the population sizes and the complexity of the genomes. The novel ORFs, including sORFs, identified from single-nucleotide polymorphisms are supported by protein mass spectrometry evidence comparable to that of the annotated ORFs. The application of OrfPP to tetraploid cotton and hexaploid wheat genomes successfully identified 76.17% and 87.43% of the annotated ORFs in the genomes, respectively, as well as 4704 sORFs, including 1182 upstream and 2110 downstream ORFs in cotton and 5025 sORFs, including 232 upstream and 234 downstream ORFs in wheat. Overall, we propose an alternative and supplementary approach for ORF prediction that can extend the studies of sORFs to more complex genomes.

Experimental and Theoretical Studies on Long Alkyl Chain-Bearing Dibenzotriazole Ionic Liquids as Eco-friendly Corrosion Inhibitors in Aqueous Hydrochloride Acid.

Three long alkyl chain-bearing dibenzotriazole ionic liquids (BTA-R-BTA, R = 8, 12, and 16) were synthesized with high yield (>98%) through a simple and eco-friendly process. Their anticorrosion performance for Q235 carbon steel in 6 M hydrochloride acid was comprehensively evaluated by weight loss tests, electrochemical methods (potentiodynamic polarization and electrochemical impedance spectroscopy), and surface analysis techniques. As the length of the alkyl chain increased, the maximum corrosion inhibition efficiency enhanced from 55.02% (for BTA-8-BTA at 1.2 mM) to 97.10% (for BTA-12-BTA at 0.3 mM) and 98.84% (for BTA-16-BTA at 0.3 mM). Density functional theory calculation indicated that the alkyl chain length had little influence on the inhibitors' electronic structures, while molecular dynamics simulations revealed that the thickness, surface coverage, and compactness of adsorption films formed at the metal-electrolyte interface increased with the elongated alkyl chain. Corrosion inhibition efficiency is strongly correlated with the structures of the adsorption film.

Halogen-Free Functional Quaternary Ammonium-Based Ionic Liquid as an Ecofriendly Corrosion Inhibitor for Q235 Steel in Acids.

A halogen-free quaternary ammonium-based ionic liquid functionalized with benzotriazole, BTA-16-BTA, was synthesized. Its anticorrosion effects on Q235 steel were evaluated in two different acids (6 M HCl or 1 M H3PO4) by weight loss and electrochemical tests. BTA-16-BTA shows the best performance at 30 °C with the highest inhibition efficiencies of 98.84% in 6 M HCl and 96.40% in 1 M H3PO4. The adsorption behavior of BTA-16-BTA molecules on Q235 steel in HCl solution obeys the Langmuir isotherm with an adsorption energy of about -40 kJ·mol-1, which implies chemisorption. Quantum chemistry calculation indicates that the chemical adsorption originated from the injection of π-electrons from inhibitor molecules into empty 3d orbitals of Fe atoms. The tight adsorption of inhibitor molecules and associated dehydration of the steel surface promoted the corrosion inhibition in HCl solutions. In H3PO4 solutions, passivation by phosphate anions and adsorption of inhibitor molecules contributed synergistically to the excellent anticorrosion performance.

Formation mechanism of off-flavor and the inhibition regulatory strategies in the algal oil-loaded emulsions-a review.

Algal oil rich in docosahexaenoic acid is easily oxidized and degraded to produce volatile short-chain compounds, leading to the deterioration of product flavor. Currently, the emulsion delivery of algal oil provides a promising approach to minimize oxidative deterioration and conceal its off-flavor. However, algal oil emulsions would also experience unanticipated oxidation as a result of the large specific surface area between the aqueous phase and the oil phase. The current paper offers a mechanism overview behind off-flavor formation in algal oil emulsions and explores corresponding strategies for the inhibition regulation. Additionally, the paper delves into the factors influencing lipid oxidation and the perception of off-flavors in such emulsions. To mitigate the development of off-flavors in algal oil emulsions resulting from oxidation, it is crucial to decline the likelihood of lipid oxidation and proactively prevent the creation of off-flavors whenever possible. Minimizing the release of volatile off-flavor compounds that are inevitably generated is also considered effective for weakening off-flavor. Moreover, co-encapsulation with particular desirable aroma substances could improve the overall flavor characteristics of emulsions.

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

Application of Circular RNA Circ_0071662 in the Diagnosis and Prognosis of Hepatocellular Carcinoma and Its Response to Radiotherapy.

BACKGROUND: Although the involvement of circular RNA Circ_0071662 in bladder cancer and esophageal cancer has been reported, its role in hepatocellular carcinoma (HCC) is unclear. The presented research aimed to study its role in HCC. METHODS: This study enrolled 60 HCC patients (advanced stage), 60 hepatic angiomyolipoma patients, 60 liver abscess patients, 60 hypertrophic cardiomyopathy patients, 60 focal nodular hyperplasia patients, and 60 healthy controls (HCs). Plasma samples were obtained from all participants prior to treatment. HCC and paired nontumor samples were collected from HCC patients. HCC patients received radiotherapy and plasma samples were also collected after treatment. Gene expression was analyzed by RT-qPCR. The role of Circ_0071662 in the diagnosis of HCC was evaluated by ROC curve analysis. RESULTS: Compared to HCs, decreased plasma expression levels of Circ_0071662 were only observed in HCC patients, but not in other patient groups. HCC tissues also exhibited decreased expression levels of Circ_0071662 compared to that in nontumor samples. Decreased plasma expression levels of Circ_0071662 separated HCC patients from HCs and other patient groups. After radiotherapy, 28 patients developed radioresistance (RR) and the rest showed no RR. Decreased plasma expression levels of Circ_0071662 were closely associated with patients' poor survival. Compared to pretreatment level, decreased plasma expression levels of Circ_0071662 were only observed in RR group. The expression levels of Circ_0071662 in plasma and tissues were closely associated with patients' tumor metastasis and tumor size. CONCLUSION: Circ_0071662 was downregulated in HCC and may serve as a potential biomarker to improve the diagnosis of HCC. Moreover, downregulation of Circ_0071662 is likely correlated to the development of radioresistance.

Does seasonality affect snoring? A study based on international data from the past decade.

BACKGROUND: Though snoring is often regarded as a harmless condition that coincides with sound sleep, it is a sleep disorder that can be a potential indicator of more severe conditions such as sleep apnea syndrome. In the present study, we investigated the association between seasonal variations and snoring. METHOD: Search index for snoring (SIS) data were obtained from Google Trends and Baidu Index. SIS data were collected for the USA, India, Germany, Russia, Japan, Australia, China, and Brazil from 2011 to 2020, with the periodicity of the relationship between seasonal time series data and snoring evaluated using a time series decomposition model. RESULT: The highest average SIS growth rates from 2011 to 2020 were observed for Brazil, Japan, and Germany, with average SIS values of 94%, 68%, and 49%, respectively. The SIS of the USA, Russia, Japan, Brazil, Australia, Germany, and India increased by 22.3%, 12.4%, 11.9%, 35.4%, 12.3%, 28.0%, and 55.8%, respectively, in comparison with their SIS values in 2019, whereas for China, it decreased by 13.7%. Relative to countries in the southern hemisphere, those in the northern hemisphere showed comparable SIS trends, increasing from September to February and decreasing from March to August. CONCLUSION: The SIS data showed cyclical changes over the study period. The search index for snoring increased during the cold season or the heating season, suggesting that snoring is associated with seasonal changes.

Enhancing Resource Sharing and Access Control for VNF Instantiation with Blockchain.

In the realm of Network Function Virtualization (NFV), Virtual Network Functions (VNFs) are crucial software entities that require execution on virtualized hardware infrastructure. Deploying a Service Function Chain (SFC) requires multiple steps for instantiating VNFs to analyze, request, deploy, and monitor resources. It is well recognized that the sharing of infrastructure resources among different VNFs will enhance resource utilization. However, conventional mechanisms for VNF sharing often neglect the interests of both VNF instances and infrastructure providers. In this context, this paper presents a blockchain-based framework that focuses on resource sharing and access control, with a particular emphasis on ensuring profitability during VNF instantiation. Additionally, a resource sharing game model and a novel greedy matching algorithm are introduced to optimize the benefits for both VNF instances and infrastructure resource providers. Furthermore, a blockchain-based access control mechanism is designed to securely store keys and provide fine-grained access control. The experimental results demonstrate that the proposed resource sharing game model and greedy matching algorithm promote healthy competition among resource owners and facilitate effective bargaining between resource owners and infrastructure providers. In comparison to the standard Stackelberg game solution, our proposed method achieves up to an 8.1 times performance improvement while sacrificing fewer optimal social utility values. Furthermore, compared to other CP-ABE methods, the proposed approach enhances security within a blockchain-based framework while maintaining an excellent encryption efficiency and a moderate decryption efficiency.

Structural Health Monitoring Using a New Type of Distributed Fiber Optic Smart Textiles in Combination with Optical Frequency Domain Reflectometry (OFDR): Taking a Pedestrian Bridge as Case Study.

Distributed fiber optic sensors (DFOS) have become a new method for continuously monitoring infrastructure status. However, the fiber's fragility and the installation's complexity are some of the main drawbacks of this monitoring approach. This paper aims to overcome this limitation by embedding a fiber optic sensor into a textile for a faster and easier installation process. To demonstrate its feasibility, the smart textile was installed on a pedestrian bridge at the University of Massachusetts Lowell. In addition, dynamic strain data were collected for two different years (2021 and 2022) using Optical Frequency Domain Reflectometry (OFDR) and compared, to determine the variability of the data after one year of installation. We determined that no significant change was observed in the response pattern, and the difference between the amplitude of both datasets was 14% (one person jumping on the bridge) and 43% (two people jumping) at the first frequency band. This result shows the proposed system's functionality after one year of installation, as well as its potential use for traffic monitoring.

Composite Bridge Girders Structure Health Monitoring Based on the Distributed Fiber Sensing Textile.

Distributed structure health monitoring has been a hot research topic in recent years, and optic fiber sensors are largely developed for the advantages of high sensitivity, better spatial resolution, and small sensor size. However, the limitation of fibers in installation and reliability has become one of the major drawbacks of this technology. This paper presents a fiber optic sensing textile and a new installation method inside bridge girders to address those shortcomings in fiber sensing systems. The sensing textile was utilized to monitor strain distribution in the Grist Mill Bridge located in Maine based on Brillouin Optical Time Domain Analysis (BOTDA). A modified slider was developed to increase the efficiency of installation in the confined bridge girders. The bridge girder's strain response was successfully recorded by the sensing textile during the loading tests that involved four trucks on the bridge. The sensing textile demonstrated the capability to differentiate separated loading locations. These results demonstrate a new way of installing fiber optic sensors and the potential applications of fiber optic sensing textiles in structural health monitoring.

Machine learning-based radiomics for histological classification of parotid tumors using morphological MRI: a comparative study.

OBJECTIVES: To evaluate the effectiveness of machine learning models based on morphological magnetic resonance imaging (MRI) radiomics in the classification of parotid tumors. METHODS: In total, 298 patients with parotid tumors were randomly assigned to a training and test set at a ratio of 7:3. Radiomics features were extracted from the morphological MRI images and screened using the Select K Best and LASSO algorithm. Three-step machine learning models with XGBoost, SVM, and DT algorithms were developed to classify the parotid neoplasms into four subtypes. The ROC curve was used to measure the performance in each step. Diagnostic confusion matrices of these models were calculated for the test cohort and compared with those of the radiologists. RESULTS: Six, twelve, and eight optimal features were selected in each step of the three-step process, respectively. XGBoost produced the highest area under the curve (AUC) for all three steps in the training cohort (0.857, 0.882, and 0.908, respectively), and for the first step in the test cohort (0.826), but produced slightly lower AUCs than SVM in the latter two steps in the test cohort (0.817 vs. 0.833, and 0.789 vs. 0.821, respectively). The total accuracies of XGBoost and SVM in the confusion matrices (70.8% and 59.6%) outperformed those of DT and the radiologist (46.1% and 49.2%). CONCLUSION: This study demonstrated that machine learning models based on morphological MRI radiomics might be an assistive tool for parotid tumor classification, especially for preliminary screening in absence of more advanced scanning sequences, such as DWI. KEY POINTS: • Machine learning algorithms combined with morphological MRI radiomics could be useful in the preliminary classification of parotid tumors. • XGBoost algorithm performed better than SVM and DT in subtype differentiation of parotid tumors, while DT seemed to have a poor validation performance. • Using morphological MRI only, the XGBoost and SVM algorithms outperformed radiologists in the four-type classification task for parotid tumors, thus making these models a useful assistant diagnostic tool in clinical practice.

A salivary effector enables whitefly to feed on host plants by eliciting salicylic acid-signaling pathway.

Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant's defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.

Fiber Lateral Pressure Sensor Based on Vernier- Effect Improved Fabry-Perot Interferometer.

A fiber optic pressure sensor that can survive 2200 psi and 140 °C was developed. The sensor's pressure sensitivity was measured to be 14 times higher than bare FBG when tested inside stacks of ultra-high-molecular-weight polyethylene (UHMWPE) composite fabric. The sensitivity can be further improved 6-fold through the Vernier effect. Its tiny sensing length (hundreds of microns) and uniform outer diameter (125 µm) make it a suitable candidate for real-time point pressure monitoring under harsh environments with limited space, such as in composite-forming procedures.

An Algorithm with Iteration Uncertainty Eliminate Based on Geomagnetic Fingerprint under Mobile Edge Computing for Indoor Localization.

Indoor localization problems are difficult due to that the information, such as WLAN and GPS, cannot achieve enough precision for indoor issues. This paper presents a novel indoor localization algorithm, GeoLoc, with uncertainty eliminate based on fusion of acceleration, angular rate, and magnetic field sensor data. The algorithm can be deployed in edge devices to overcome the problems of insufficient computing resources and long delay caused by high complexity of location calculation. Firstly, the magnetic map is built and magnetic values are matched. Secondly, orientation updating and position selection are iteratively executed using the fusion data, which gradually reduce uncertainty of orientation. Then, we filter the trajectory from a path set. By gradually reducing uncertainty, GeoLoc can bring a high positioning precision and a smooth trajectory. In addition, this method has an advantage in that it does not rely on any infrastructure such as base stations and beacons. It solves the common problems regarding the non-uniqueness of the geomagnetic fingerprint and the deviation of the sensor measurement. The experimental results show that our algorithm achieves an accuracy of less than 2.5 m in indoor environment, and the positioning results are relatively stable. It meets the basic requirements of indoor location-based services (LBSs).

Fiber Optic Sensing Textile for Strain Monitoring in Composite Substrates.

Composite polymers have become widely used in industries such as the aerospace, automobile, and civil construction industries. Continuous monitoring is essential to optimize the composite components' performance and durability. This paper describes the concept of a distributed fiber optic smart textile (DFOST) embedded into a composite panel that can be implemented during the fabrication process of bridges, planes, or vehicles without damaging the integrity of the composite. The smart textile used an embroidery method to create DFOST for easy installation between composite laminates. It also allows different layout patterns to provide two- or three-dimensional measurements. The DFOST system can then measure strain, temperature, and displacement changes, providing critical information for structural assessment. The DFOST was interrogated by using an optical frequency domain reflectometry (OFDR). It could measure strain variation during the dynamic and static test with a spatial resolution of 2 mm and a minimum strain resolution of 10 µÏµ. This paper focuses on the study of strain measurement.

Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common types of cancer that cause a substantial number of cancer-related deaths. Our previous study has revealed that makorin ring finger protein 3 (MKRN3) may act as a key regulator of the SCCHN tumorigenesis; however, its specific role in SCCHN progression has not been reported. METHODS: The Cancer Genome Atlas (TCGA) data analysis and quantitative polymerase chain reaction (qPCR) were used to quantify the MKRN3 mRNA expression levels in SCCHN; immunohistochemical staining or immunoblotting analyses were performed to detect MKRN3 protein expression. Kaplan-Meier plotter was used to assess the prognostic values of MKRN3 in terms of overall survival and disease-free survival. The expression differences based on various clinicopathological features were evaluated using subgroup analysis and forest map analysis. The regulatory mechanism of MKRN3 was further investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, STRING was used to perform a co-expression and enrichment analysis for MKRN3. Homologous modeling, molecular docking, and western blot analyses were performed to investigate the relationship between MKRN3 and its potential target gene P53. RESULTS: MKRN3 was ectopically expressed between cancerous and noncancerous SCCHN tissues, and its expression level was tightly associated with high T classifications as well as advanced clinical stages. qPCR analysis revealed that MKRN3 was upregulated in the SCCHN cell line. Moreover, Kaplan-Meier and Cox regression analyses indicated that SCCHN patients with high MKRN3 expression had poorer prognosis and that MKRN3 was a potential prognostic marker for SCCHN. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we determined that MKRN3 may be involved in the regulation of synthesis and metabolism and cell growth, death and motility, as well as cancer pathways associated with SCCHN progression. Mechanism investigation further revealed that P53, a potential target of MKRN3, may be involved in the SCCHN tumorigenesis mediated by MKRN3. CONCLUSIONS: We performed a comprehensive evaluation of the clinical significance of MKRN3 and explored its underlying mechanisms. We concluded that MKRN3 represents a valuable predictive biomarker and potential therapeutic target in SCCHN.

SHARPIN stabilizes ß-catenin through a linear ubiquitination-independent manner to support gastric tumorigenesis.

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/ß-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. METHODS: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/ß-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of ß-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. RESULTS: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with ß-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase ß-Trcp1 for ß-catenin binding, thereby decreasing ß-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner ß-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with ß-catenin expression levels. CONCLUSIONS: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/ß-catenin signaling via SHARPIN-mediated stabilization of ß-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive ß-catenin signaling in a subset of human gastric cancers.