Targeting UBE4A Revives Viperin Protein in Epithelium to Enhance Host Antiviral Defense.

Mutation and prevalence of pathogenic viruses prompt the development of broad-spectrum antiviral strategies. Viperin is a potent antiviral protein that inhibits a broad range of viruses. Unexpectedly, we found that Viperin protein production in epithelium is defective in response to both viruses and interferons (IFNs). We further revealed that viruses and IFNs stimulate expression of the acetyltransferase HAT1, which induces Lys197-acetylation on Viperin. Viperin acetylation in turn recruits UBE4A that stimulates K6-linked polyubiquitination at Lys206 of Viperin, leading to Viperin protein degradation. Importantly, UBE4A deficiency restores Viperin protein production in epithelium. We then designed interfering peptides (IPs) to inhibit UBE4A binding with Viperin. We found that VIP-IP3 rescues Viperin protein production in epithelium and therefore enhances cellular antiviral activity. VIP-IP3 renders mice more resistant to viral infection. These findings could provide strategies for both enhancing host broad-spectrum antiviral response and improving the efficacy of IFN-based antiviral therapy.

High salt activates p97 to reduce host antiviral immunity by restricting Viperin induction.

High-salt diets have recently been implicated in hypertension, cardiovascular disease, and autoimmune disease. However, whether and how dietary salt affects host antiviral response remain elusive. Here, we report that high salt induces an instant reduction in host antiviral immunity, although this effect is compromised during a long-term high-salt diet. Further studies reveal that high salt stimulates the acetylation at Lys663 of p97, which promotes the recruitment of ubiquitinated proteins for proteasome-dependent degradation. p97-mediated degradation of the deubiquitinase USP33 results in a deficiency of Viperin protein expression during viral infection, which substantially attenuates host antiviral ability. Importantly, switching to a low-salt diet during viral infection significantly enhances Viperin expression and improves host antiviral ability. These findings uncover dietary salt-induced regulation of ubiquitinated cellular proteins and host antiviral immunity, and could offer insight into the daily consumption of salt-containing diets during virus epidemics.

Impact of ERAS on Hysteromyomectomy: A Study on Anxiety, Depression, and Ovarian Function.

Objective: To analyze the application of the Enhanced Recovery After Surgery (ERAS) nursing mode in patients undergoing radical cystectomy with urinary diversion. Methods: A retrospective analysis was conducted on clinical data of 72 patients with bladder cancer who underwent "robot-assisted laparoscopic radical cystectomy + urinary diversion" in Nanjing University Medical College Affiliated Gulou Hospital between January 2021 and January 2023. All patients met the complete inclusion criteria. They were divided into a control group (n=35) and a observation group (n=37). Patients in the control group received routine rehabilitation nursing intervention, while patients in the study group received ERAS nursing mode intervention. The outcomes include time to first intake, time to first defecation, duration of enteral nutrition, duration of antibiotic use, duration of drainage tube placement, length of hospital stay, psychological status Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), quality of life (SF-36) scores, sexual function assessment Arizona Sexual Experience Scale (ASEX), International Index of Erectile Function-5 (IIEF-5), and occurrence of complications were compared between the two groups. Results: In the observation group, perioperative indicators, psychological status, quality of life, sexual function, and complication rates were notably improved compared to the control group (all P < .05). Conclusion: ERAS nursing mode intervention in bladder cancer patients exhibited significant effectiveness, enhancing postoperative recovery, reducing anxiety and depression, improving quality of life and sexual function, and lowering complication risks. These findings support the clinical merit and applicability of ERAS nursing in urinary diversion for bladder cancer patients.

Channel Features and API Frequency-Based Transformer Model for Malware Identification.

Malicious software (malware), in various forms and variants, continues to pose significant threats to user information security. Researchers have identified the effectiveness of utilizing API call sequences to identify malware. However, the evasion techniques employed by malware, such as obfuscation and complex API call sequences, challenge existing detection methods. This research addresses this issue by introducing CAFTrans, a novel transformer-based model for malware detection. We enhance the traditional transformer encoder with a one-dimensional channel attention module (1D-CAM) to improve the correlation between API call vector features, thereby enhancing feature embedding. A word frequency reinforcement module is also implemented to refine API features by preserving low-frequency API features. To capture subtle relationships between APIs and achieve more accurate identification of features for different types of malware, we leverage convolutional neural networks (CNNs) and long short-term memory (LSTM) networks. Experimental results demonstrate the effectiveness of CAFTrans, achieving state-of-the-art performance on the mal-api-2019 dataset with an F1 score of 0.65252 and an AUC of 0.8913. The findings suggest that CAFTrans improves accuracy in distinguishing between various types of malware and exhibits enhanced recognition capabilities for unknown samples and adversarial attacks.

Elevated post-ischemic ubiquitination results from suppression of deubiquitinase activity and not proteasome inhibition.

Cerebral ischemia-reperfusion increases intraneuronal levels of ubiquitinated proteins, but the factors driving ubiquitination and whether it results from altered proteostasis remain unclear. To address these questions, we used in vivo and in vitro models of cerebral ischemia-reperfusion, in which hippocampal slices were transiently deprived of oxygen and glucose to simulate ischemia followed by reperfusion, or the middle cerebral artery was temporarily occluded in mice. We found that post-ischemic ubiquitination results from two key steps: restoration of ATP at reperfusion, which allows initiation of protein ubiquitination, and free radical production, which, in the presence of sufficient ATP, increases ubiquitination above pre-ischemic levels. Surprisingly, free radicals did not augment ubiquitination through inhibition of the proteasome as previously believed. Although reduced proteasomal activity was detected after ischemia, this was neither caused by free radicals nor sufficient in magnitude to induce appreciable accumulation of proteasomal target proteins or ubiquitin-proteasome reporters. Instead, we found that ischemia-derived free radicals inhibit deubiquitinases, a class of proteases that cleaves ubiquitin chains from proteins, which was sufficient to elevate ubiquitination after ischemia. Our data provide evidence that free radical-dependent deubiquitinase inactivation rather than proteasomal inhibition drives ubiquitination following ischemia-reperfusion, and as such call for a reevaluation of the mechanisms of post-ischemic ubiquitination, previously attributed to altered proteostasis. Since deubiquitinase inhibition is considered an endogenous neuroprotective mechanism to shield proteins from oxidative damage, modulation of deubiquitinase activity may be of therapeutic value to maintain protein integrity after an ischemic insult.

Prohibitin S-Nitrosylation Is Required for the Neuroprotective Effect of Nitric Oxide in Neuronal Cultures.

Prohibitin (PHB) is a critical protein involved in many cellular activities. In brain, PHB resides in mitochondria, where it forms a large protein complex with PHB2 in the inner TFmembrane, which serves as a scaffolding platform for proteins involved in mitochondrial structural and functional integrity. PHB overexpression at moderate levels provides neuroprotection in experimental brain injury models. In addition, PHB expression is involved in ischemic preconditioning, as its expression is enhanced in preconditioning paradigms. However, the mechanisms of PHB functional regulation are still unknown. Observations that nitric oxide (NO) plays a key role in ischemia preconditioning compelled us to postulate that the neuroprotective effect of PHB could be regulated by NO. Here, we test this hypothesis in a neuronal model of ischemia-reperfusion injury and show that NO and PHB are mutually required for neuronal resilience against oxygen and glucose deprivation stress. Further, we demonstrate that NO post-translationally modifies PHB through protein S-nitrosylation and regulates PHB neuroprotective function, in a nitric oxide synthase-dependent manner. These results uncover the mechanisms of a previously unrecognized form of molecular regulation of PHB that underlies its neuroprotective function.SIGNIFICANCE STATEMENT Prohibitin (PHB) is a critical mitochondrial protein that exerts a potent neuroprotective effect when mildly upregulated in mice. However, how the neuroprotective function of PHB is regulated is still unknown. Here, we demonstrate a novel regulatory mechanism for PHB that involves nitric oxide (NO) and shows that PHB and NO interact directly, resulting in protein S-nitrosylation on residue Cys69 of PHB. We further show that nitrosylation of PHB may be essential for its ability to preserve neuronal viability under hypoxic stress. Thus, our study reveals a previously unknown mechanism of functional regulation of PHB that has potential therapeutic implications for neurologic disorders.

Small-molecule inhibitors of ubiquitin-specific protease 7 enhance type-I interferon antiviral efficacy by destabilizing SOCS1.

Type-I interferons (IFN-I) are used as common antiviral drugs for a range of viral diseases in clinic. However, the antiviral efficacy of IFN-I is largely restricted by negative regulators of IFN-I signaling in cells. Therefore, identification of intracellular inhibitors of IFN-I signaling is important for developing novel targets to improve IFN-I antiviral therapy. In this study, we report that the deubiquitinase ubiquitin-specific protease 7 (USP7) negatively regulates IFN-I-mediated antiviral activity. USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of Janus kinase-signal transducer and activator of transcription 1 signaling. Interestingly, viral infection up-regulates USP7 and therefore facilitates viral immune evasion. Importantly, the USP7 small-molecule inhibitors P5091 and P22077 inhibit SOCS1 expression and enhance IFN-I antiviral efficacy. Our findings identify a novel regulator of IFN-I antiviral activity and reveal that USP7 inhibitors could be potential enhancement agents for improving IFN-I antiviral therapy.

Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome.

During RNA virus infection, the adaptor protein MAVS recruits TRAF3 and TRAF6 to form a signalosome, which is critical to induce the production of type I interferons (IFNs) and proinflammatory cytokines. While activation of the MAVS/TRAF3/TRAF6 signalosome is well studied, the negative regulation of the signalosome remains largely unknown. Here we report that RNA viruses specifically promote the deubiquitinase OTUD1 expression by NF-κB-dependent mechanisms at the early stage of viral infection. Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination. Importantly, RNA virus infection promotes the binding of Smurf1 to MAVS, TRAF3 and TRAF6, which leads to ubiquitination-dependent degradation of every component of the MAVS/TRAF3/TRAF6 signalosome and subsequent potent inhibition of IFNs production. Consistently, OTUD1-deficient mice produce more antiviral cytokines and are more resistant to RNA virus infection. Our findings reveal a novel immune evasion mechanism exploited by RNA viruses, and elucidate a negative feedback loop of MAVS/TRAF3/TRAF6 signaling mediated by the OTUD1-Smurf1 axis during RNA virus infection.

ATXN3 Positively Regulates Type I IFN Antiviral Response by Deubiquitinating and Stabilizing HDAC3.

Ataxin-3 (ATXN3) belongs to the Josephin family of deubiquitinases. So far, ATXN3 is majorly linked to the neurodegenerative disease, Machado-Joseph disease. The role of ATXN3 in the antiviral function has not been explored, and the in vivo deubiquitinating activity of ATXN3 remains largely unknown. In this study, we report that ATXN3 is an important positive regulator of type I IFN (IFN-I)-mediated antiviral activity in murine primary lung cells and human epithelial and fibroblast cell lines. We clarify that ATXN3 does not promote IFN-I production, but enhances the IFN-I-mediated signaling pathway. Furthermore, ATXN3 physically interacts with histone deacetylase 3 (HDAC3) and upregulates the level of HDAC3 protein. Moreover, ATXN3 deubiquitinates HDAC3, thereby enhancing HDAC3 protein stability. Interestingly, the interaction between ATXN3 and HDAC3 increases during viral infection, which promotes IFN-I-induced signaling in murine primary lung cells. Finally, we reveal the ATXN3/HDAC3 axis-mediated regulation of IFN-I antiviral response. These findings reveal a novel biological function of ATXN3 and an important antiviral mechanism by which the deubiquitinase ATXN3 positively regulates IFN-I antiviral response, and they may provide a novel strategy for enhancing IFN-based antiviral therapy.

Lack of patient education is risk factor of disease flare in patients with systemic lupus erythematosus in China.

BACKGROUND: To explore the inadequacies of health service and its impact on clinical outcomes of patients with systemic lupus erythematosus (SLE) in China. METHODS: A total of 210 SLE patients were randomly recruited between January 2017 and January 2018. Each patient received self-report questionnaires to assess medication adherence [Compliance Questionnaire for Rheumatology (CQR)], beliefs about medicines [Beliefs about Medicines Questionnaire (BMQ)] and satisfaction about medicine information [the Satisfaction with Information about Medicines Scale (SIMS)]. Associations between SLE disease activity index (SLEDAI-2 K) and observed factors were analyzed by multiple logistic regression. RESULTS: Based on CQR, only 28.10% patients were adherent. The score of BMQ was 2.85 ± 5.42, and merely 32.38% patients were satisfied with the information about their prescribed medicines. Disease activity was associated with SIMS, EuroQol five-dimensions [EQ5D], Systemic Lupus International Collaborating Clinics (SLICC), depression, use of NSAID (P ≤ 0.05). Remission of disease was positively correlated with SIMS (OR = 0.16, 95% CI: [0.06, 0.40]), and BMQ (OR = 0.64, 95%CI: [0.43, 0.94]). CONCLUSION: In this study, the scores of BMQ and SIMS were low, implying defects in the patient education of health service system, which led to disease flare in Chinese SLE patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03024307 . Registered January 18, 2017.

Multi-Server Multi-User Multi-Task Computation Offloading for Mobile Edge Computing Networks.

This paper studies mobile edge computing (MEC) networks where multiple wireless devices (WDs) offload their computation tasks to multiple edge servers and one cloud server. Considering different real-time computation tasks at different WDs, every task is decided to be processed locally at its WD or to be offloaded to and processed at one of the edge servers or the cloud server. In this paper, we investigate low-complexity computation offloading policies to guarantee quality of service of the MEC network and to minimize WDs' energy consumption. Specifically, both a linear programing relaxation-based (LR-based) algorithm and a distributed deep learning-based offloading (DDLO) algorithm are independently studied for MEC networks. We further propose a heterogeneous DDLO to achieve better convergence performance than DDLO. Extensive numerical results show that the DDLO algorithms guarantee better performance than the LR-based algorithm. Furthermore, the DDLO algorithm generates an offloading decision in less than 1 millisecond, which is several orders faster than the LR-based algorithm.

Estrogen receptor beta modulates permeability transition in brain mitochondria.

Recent evidence highlights a role for sex and hormonal status in regulating cellular responses to ischemic brain injury and neurodegeneration. A key pathological event in ischemic brain injury is the opening of a mitochondrial permeability transition pore (MPT) induced by excitotoxic calcium levels, which can trigger irreversible damage to mitochondria accompanied by the release of pro-apoptotic factors. However, sex differences in brain MPT modulation have not yet been explored. Here, we show that mitochondria isolated from female mouse forebrain have a lower calcium threshold for MPT than male mitochondria, and that this sex difference depends on the MPT regulator cyclophilin D (CypD). We also demonstrate that an estrogen receptor beta (ERß) antagonist inhibits MPT and knockout of ERß decreases the sensitivity of mitochondria to the CypD inhibitor, cyclosporine A. These results suggest a functional relationship between ERß and CypD in modulating brain MPT. Moreover, co-immunoprecipitation studies identify several ERß binding partners in mitochondria. Among these, we investigate the mitochondrial ATPase as a putative site of MPT regulation by ERß. We find that previously described interaction between the oligomycin sensitivity-conferring subunit of ATPase (OSCP) and CypD is decreased by ERß knockout, suggesting that ERß modulates MPT by regulating CypD interaction with OSCP. Functionally, in primary neurons and hippocampal slice cultures, modulation of ERß has protective effects against glutamate toxicity and oxygen glucose deprivation, respectively. Taken together, these results reveal a novel pathway of brain MPT regulation by ERß that could contribute to sex differences in ischemic brain injury and neurodegeneration.

Prohibitin is a positive modulator of mitochondrial function in PC12 cells under oxidative stress.

Prohibitin (PHB) is a ubiquitously expressed and evolutionarily conserved mitochondrial protein with multiple functions. We have recently shown that PHB up-regulation offers robust protection against neuronal injury in models of cerebral ischemia in vitro and in vivo, but the mechanism by which PHB affords neuroprotection remains to be elucidated. Here, we manipulated PHB expression in PC12 neural cells to investigate its impact on mitochondrial function and the mechanisms whereby it protects cells exposed to oxidative stress. PHB over-expression promoted cell survival, whereas PHB down-regulation diminished cell viability. Functionally, manipulation of PHB levels did not affect basal mitochondrial respiration, but it increased spare respiratory capacity. Moreover, PHB over-expression preserved mitochondrial respiratory function of cells exposed to oxidative stress. Preserved respiratory capacity in differentiated PHB over-expressing cells exposed to oxidative stress was associated with an elongated mitochondrial morphology, whereas PHB down-regulation enhanced fragmentation. Mitochondrial complex I oxidative degradation was attenuated by PHB over-expression and increased in PHB knockdown cells. Changes in complex I degradation were associated with alterations of respiratory chain supercomplexes. Furthermore, we showed that PHB directly interacts with cardiolipin and that down-regulation of PHB results in loss of cardiolipin in mitochondria, which may contribute to destabilizing respiratory chain supercomplexes. Taken together, these data demonstrate that PHB modulates mitochondrial integrity and bioenergetics under oxidative stress, and suggest that the protective effect of PHB is mediated by stabilization of the mitochondrial respiratory machinery and its functional capacity, by the regulation of cardiolipin content. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

MCPIP1 is a positive regulator of type I interferons antiviral activity.

Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity. We found that MCPIP1 can promote innate antiviral immunity independently of both its RNase and deubiquitinase activity. Furthermore, we reveal that MCPIP1 is an IFN-induced positive feedback signal molecule which promotes IFN-I-mediated antiviral efficacy. Mechanistically, MCPIP1 does not affect the activation of JAK/STAT upstream of IFN-I signaling, but significantly promotes IFN-I signaling by enhancing ISRE promoter activity and expression of interferon-stimulated genes (ISGs). And MCPIP1-mediated activation of IFN-I signaling is independently of its RNase and deubiquitinase activity. These findings uncover a novel innate antiviral mechanism mediated by the IFN-MCPIP1 axis, and may provide potential targets for enhancing IFNs antiviral therapy.

Deubiquitinase USP2a Sustains Interferons Antiviral Activity by Restricting Ubiquitination of Activated STAT1 in the Nucleus.

STAT1 is a critical transcription factor for regulating host antiviral defenses. STAT1 activation is largely dependent on phosphorylation at tyrosine 701 site of STAT1 (pY701-STAT1). Understanding how pY701-STAT1 is regulated by intracellular signaling remains a major challenge. Here we find that pY701-STAT1 is the major form of ubiquitinated-STAT1 induced by interferons (IFNs). While total STAT1 remains relatively stable during the early stages of IFNs signaling, pY701-STAT1 can be rapidly downregulated by the ubiquitin-proteasome system. Moreover, ubiquitinated pY701-STAT1 is located predominantly in the nucleus, and inhibiting nuclear import of pY701-STAT1 significantly blocks ubiquitination and downregulation of pY701-STAT1. Furthermore, we reveal that the deubiquitinase USP2a translocates into the nucleus and binds to pY701-STAT1, and inhibits K48-linked ubiquitination and degradation of pY701-STAT1. Importantly, USP2a sustains IFNs-induced pY701-STAT1 levels, and enhances all three classes of IFNs- mediated signaling and antiviral activity. To our knowledge, this is the first identified deubiquitinase that targets activated pY701-STAT1. These findings uncover a positive mechanism by which IFNs execute efficient antiviral signaling and function, and may provide potential targets for improving IFNs-based antiviral therapy.

Deubiquitinase USP33 is negatively regulated by ß-TrCP through ubiquitin-dependent proteolysis.

Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and therefore plays important roles in controlling cell signaling and disease progression. The Skp1-Cul1-F-box ubiquitin ligase ß-TrCP is recognized as an important negative regulator for numerous key signaling proteins. Recently, the deubiquitinases (DUBs) have turned out to be essential to regulate signaling pathways related to human diseases. However, whether ß-TrCP is able to regulate the deubiquitinase family members remains largely unexplored. Here, we found that ß-TrCP downregulated cellular levels of endogenous USP33. We also revealed that ß-TrCP interacted with USP33 independently of the classic binding motif for ß-TrCP, and mediated USP33 degradation via the ubiquitin proteasome pathway. Furthermore, we found that the WD40 motif of ß-TrCP and 201-400 amino acid motif of USP33 are required for the interaction between ß-TrCP and USP33. Consequently, ß-TrCP attenuated USP33-mediated inhibition of cell proliferation and cell invasion. Taken together, our study clarified that the E3 ligase ß-TrCP regulates cellular USP33 levels by the ubiquitin-proteasomal proteolysis.

RFID Data-Driven Vehicle Speed Prediction via Adaptive Extended Kalman Filter.

The traditional speed prediction generally utilizes the Global Position System (GPS) and video images, and thus, the prediction precision mainly depends on environmental factors (i.e., weather, ionosphere, troposphere, air, and electromagnetic waves). We study the Radio Frequency Identification (RFID) data-driven vehicle speed prediction and proposed an improved extended kalman filter (i.e., the adaptive extended kalman filter, AEKF) algorithm. Firstly, the on-board RFID reader equipped in the vehicle reads the information (i.e., current speed and time) from the tag deployed on the road. Secondly, the received information is transmitted to the on-board information processing unit, and it is demodulated and decoded into available information. Finally, based on the vehicle state space model, the AEKF algorithm is proposed to predict vehicle speed and improve the prediction results, so that the vehicle speed gradually approaches the actual vehicle speed. The simulation results show that compared with the conventional extended kalman filter (EKF) algorithm, our proposed AEKF algorithm improves the dynamic performance of the filtering and better suppresses the filtering divergence process. Moreover, the AEKF algorithm also improves the precision of the Mean Square Error (MSE) and Mean Absolute Error (MAE) by 57.4% and 32.4%, respectively.

Optimal Computational Power Allocation in Multi-Access Mobile Edge Computing for Blockchain.

Blockchain has emerged as a decentralized and trustable ledger for recording and storing digital transactions. The mining process of Blockchain, however, incurs a heavy computational workload for miners to solve the proof-of-work puzzle (i.e., a series of the hashing computation), which is prohibitive from the perspective of the mobile terminals (MTs). The advanced multi-access mobile edge computing (MEC), which enables the MTs to offload part of the computational workloads (for solving the proof-of-work) to the nearby edge-servers (ESs), provides a promising approach to address this issue. By offloading the computational workloads via multi-access MEC, the MTs can effectively increase their successful probabilities when participating in the mining game and gain the consequent reward (i.e., winning the bitcoin). However, as a compensation to the ESs which provide the computational resources to the MTs, the MTs need to pay the ESs for the corresponding resource-acquisition costs. Thus, to investigate the trade-off between obtaining the computational resources from the ESs (for solving the proof-of-work) and paying for the consequent cost, we formulate an optimization problem in which the MTs determine their acquired computational resources from different ESs, with the objective of maximizing the MTs' social net-reward in the mining process while keeping the fairness among the MTs. In spite of the non-convexity of the formulated problem, we exploit its layered structure and propose efficient distributed algorithms for the MTs to individually determine their optimal computational resources acquired from different ESs. Numerical results are provided to validate the effectiveness of our proposed algorithms and the performance of our proposed multi-access MEC for Blockchain.

Optimal Resource Allocation for Uplink Data Collection in Nonorthogonal Multiple Access Networks.

Accommodating massive connectivity for Internet of Things (IoT) applications is considered an important goal of future 5G cellular systems. Nonorthogonal multiple access (NOMA), which enables a group of mobile users to simultaneously share the same spectrum channel for transmission, provides an efficient approach to achieve the goals of spectrum-efficient data delivery. In this paper, we consider an uplink transmission in a sensor network in which a group of smart terminals (e.g., sensors) use NOMA to send their collected data to an access point. We aim to minimize the total radio resource consumption cost, including the cost for the channel usage and the cost for all senors' energy consumption to allow the sensors to complete their data delivery requirements. Specifically, we formulate a joint optimization of the decoding-order, transmit-power and time allocations to study this problem and propose an efficient algorithm to find the optimal solution. Numerical results are provided to validate our proposed algorithm and the performance advantage of our proposed joint optimization for the uplink data collection via NOMA transmission.

Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53-dependent manner.

Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer-related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT-PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK-8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA-mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual-luciferase reporter assay and ChIP-qPCR analysis. PRC1 was up-regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease-specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell-cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.