As a key infrastructure of Industry 4.0, Industrial Internet-of-Things (IIoT) promises the opportunity to build powerful industrial environments by leveraging the growing ubiquity of wired and ...wireless communication technologies. Designing a data delivery scheme in the future IIoT networks is undoubtedly a challenging task, as it should satisfy several conflicting requirements: massive-scale, data-intensive, and mission-critical, the requirements of which have motivated the desired need for feasible IIoT network architecture. In particular, the traffic characteristics of certain IIoT applications feature small-data patterns especially in typical automation control scenarios such as robot control on the downlink. In order to reduce the huge overhead associated with each individual unicast transmission of the small-data message, we propose a novel "multipoint-to-multipoint" and/or "point-to-multipoint with different contents" communication paradigm-Uni-Multi-Unicast (UMUcast), which is based-on traditional 4G technologies such as evolved Multimedia Broadcast Multicast Service (eMBMS) and Group Communication System Enablers (GCSE), and novel 5G technologies such as Multi-Access Edge Computing (MEC). For the downlink, the UMUcast transmitter can jointly encode multiple-sources' small-data messages into a single chunk at MEC equipment in conjoint with a gNB, where chunk can be one-off transmission to multiple receivers simultaneously through an eMBMS frame, whereas the chunk is decoded into multiple small-data by each individual IIoT devices separately and respectively. The simulation results show that UMUcast has remarkable improvements over conventional point-to-point unicasting in handling multi-source, multi-destination, and massive small-data delivery with characteristics of low-overhead, high-throughput, and ultra-low-latency for future 5G-based IIoT networks.
The weighted K-nearest neighbor (WKNN) algorithm is a commonly used fingerprint positioning, the difficulty of which lies in how to optimize the value of K to obtain the minimum positioning error. In ...this paper, we propose an adaptive residual weighted K-nearest neighbor (ARWKNN) fingerprint positioning algorithm based on visible light communication. Firstly, the target matches the fingerprints according to the received signal strength indication (RSSI) vector. Secondly, K is a dynamic value according to the matched RSSI residual. Simulation results show the ARWKNN algorithm presents a reduced average positioning error when compared with random forest (81.82%), extreme learning machine (83.93%), artificial neural network (86.06%), grid-independent least square (60.15%), self-adaptive WKNN (43.84%), WKNN (47.81%), and KNN (73.36%). These results were obtained when the signal-to-noise ratio was set to 20 dB, and Manhattan distance was used in a two-dimensional (2-D) space. The ARWKNN algorithm based on Clark distance and minimum maximum distance metrics produces the minimum average positioning error in 2-D and 3-D, respectively. Compared with self-adaptive WKNN (SAWKNN), WKNN and KNN algorithms, the ARWKNN algorithm achieves a significant reduction in the average positioning error while maintaining similar algorithm complexity.
Abstract
Background
Influenza virus (IV) is a leading cause of respiratory tract infections, eliciting responses from key innate immune cells such as Macrophages (MQs), Neutrophils, and Dendritic ...Cells (DCs). These cells employ diverse mechanisms to combat IV, with Inflammasomes playing a pivotal role in viral infection control. Cellular death mechanisms, including Pyroptosis, Apoptosis, and Necroptosis (collectively called PANoptosis), significantly contribute to the innate immune response.
Methods
In this updated review, we delve into the intricate relationship between PANoptosis and Inflammasomes within innate immune cells (MQs, Neutrophils, and DCs) during IV infections. We explore the strategies employed by IV to evade these immune defenses and the consequences of unchecked PANoptosis and inflammasome activation, including the potential development of severe complications such as cytokine storms and tissue damage.
Results
Our analysis underscores the interplay between PANoptosis and Inflammasomes as a critical aspect of the innate immune response against IV. We provide insights into IV's various mechanisms to subvert these immune pathways and highlight the importance of understanding these interactions to develop effective antiviral medications.
Conclusion
A comprehensive understanding of the dynamic interactions between PANoptosis, Inflammasomes, and IV is essential for advancing our knowledge of innate immune responses to viral infections. This knowledge will be invaluable in developing targeted antiviral therapies to combat IV and mitigate potential complications, including cytokine storms and tissue damage.
Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal ...model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.
For the law enforcement agencies, lawful interception is still one of the main means to intercept a suspect or address most illegal actions. Due to its centralized management, however, it is easy to ...implement in traditional networks, but the cost is high. In view of this restriction, this paper aims to exploit software-defined network (SDN) technology to contribute to the next generation of intelligent lawful interception technology, i.e., to optimize the deployment of intercept access points (IAPs) in hybrid software-defined networks where both SDN nodes and non-SDN nodes exist simultaneously. In order to deploy IAPs, this paper puts forward an improved equal-cost multi-path shortest path algorithm and accordingly proposes three SDN interception models: T interception model, ECMP-T interception model and Fermat-point interception model. Considering the location relevance of all intercepted targets and the operation and maintenance cost of operators from the global perspective, by the way, we further propose a restrictive minimum vertex cover algorithm (RMVCA) in hybrid SDN. Implementing different SDN interception algorithms based RMVCA in real-world topologies, we can reasonably deploy the best intercept access point and intercept the whole hybrid SDN with the least SDN nodes, as well as significantly optimize the deployment efficiency of IAPs and improve the intercept link coverage in hybrid SDN, contributing to the implementation of lawful interception.
Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating ...cerebral ischemia has not yet been fully elucidated.
An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin-eosin (H&E) and Nissl's staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting.
Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis.
SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.
Abstract
Background
Glioma is a common primary central nervous system tumour, and therapeutic drugs that can effectively improve the survival rate of patients in the clinic are lacking. Bufalin is ...effective in treating various tumours, but the mechanism by which it promotes the apoptosis of glioma cells is unclear. The aim of this study was to investigate the drug targets of bufalin in glioma cells and to clarify the apoptotic mechanism.
Methods
Cell viability and proliferation were evaluated by CCK-8 and colony formation assays. Then, the cell cycle and apoptosis, intracellular ion homeostasis, oxidative stress levels and mitochondrial damage were assessed after bufalin treatment. DARTS-PAGE technology was employed and LC–MS/MS was performed to explore the drug targets of bufalin in U251 cells. Molecular docking and western blotting were performed to identify potential targets. siRNA targeting Annexin A2 and the DRP1 protein inhibitor Mdivi-1 were used to confirm the targets of bufalin.
Results
Bufalin upregulated the expression of cytochrome C, cleaved caspase 3, p-Chk1 and p-p53 proteins to induce U251 cell apoptosis and cycle arrest in the S phase. Bufalin also induced oxidative stress in U251 cells, destroyed intracellular ion homeostasis, and caused mitochondrial damage. The expression of mitochondrial division-/fusion-related proteins in U251 cells was abnormal, the Annexin A2 and DRP1 proteins were translocated from the cytoplasm to mitochondria, and the MFN2 protein was released from mitochondria into the cytoplasm after bufalin treatment, disrupting the mitochondrial division/fusion balance in U251 cells.
Conclusions
Our research indicated that bufalin can cause Annexin A2 and DRP1 oligomerization on the surface of mitochondria and disrupt the mitochondrial division/fusion balance to induce U251 cell apoptosis.
Graphic Abstract
Purpose:
The incidence of uric acid (UA)-induced kidney injury is increasing owing to the high incidence of hyperuricemia in recent years. The flower of
Abelmoschus manihot
(Linneus) Medik is a ...traditional Chinese medicinal herb widely used in the treatment of some kidney diseases. In our previous study, we reported that the total extract of
A. manihot
L. flower (TEA) attenuated adriamycin-induced renal tubular cell injury. In this study, we aimed to evaluate the role of TEA in UA-induced tubular cell injury.
Methods:
Normal rat proximal epithelial NRK-52E cells were incubated with UA to mimic hyperuricemia conditions. The role of TEA in the renal tubular cells was also assessed. The cellular morphology was observed using phase-contrast microscopy, and cell viability was analyzed using the Cell Counting kit-8. Living and dead cells were stained using a Calcein-AM/PI double stain kit. The release of lactate dehydrogenase (LDH) was analyzed by LDH cytotoxicity Assay Kit. The expression of target proteins was analyzed using western blot analysis.
Results:
UA triggered NRK-52E cell injury, as evidenced by morphological changes, detachment of cells from the bottom, cell swelling, large bubbles blowing from cell membrane and loss of cell viability. UA increased release of LDH. UA induced the expression of p-ERK1/2 and the subsequent activation of caspase-8, caspase-3, and NLRP3 inflammasomes. Pyroptosis was elicited by UA after gasdermin E N-terminal (GSDME-NT) was cleaved from gasdermin E (GSDME). Z-DEVD-FMK, a caspase-3 inhibitor, suppressed the expression of both NLRP3 and GSDME-NT, but not that of caspase-8. INF39, an NLRP3 inhibitor, altered the expression of GSDME-NT expression, but not that caspase-3 and caspase-8. TEA alleviated UA-induced cell injury by suppressing ERK1/2/caspase-8/caspase-3/NLRP3/GSDME signaling.
Conclusion:
GSDME-mediated pyroptosis was involved in UA-induced renal tubular cell injury. This is the first study to report that TEA protects renal tubular epithelial cells against UA by inhibiting the ERK/1/2/caspase-8/caspase-3/NLRP3/GSDME pathway.
The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of ...this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.
A search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).
Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.
Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI.
Cyclophosphamide (CTX) is in the nitrogen mustard group of alkylating antineoplastic chemotherapeutic agents. It is one of the most frequently used antitumor agents for the treatment of a broad ...spectrum of human cancers. Thioredoxin reductase (TrxR) catalyze the NADPH-dependent reduction of thioredoxin and play an important role in multiple cellular events related to carcinogenesis including cell proliferation, apoptosis, and cell signaling. This enzyme represents a promising target for the development of cytostatic agents. The purpose of this study is to determine whether CTX could target TrxR
in vivo. Lewis lung carcinoma and solid H22 hepatoma treated with 50–250 mg/kg CTX for 3 h lost TrxR activity in a dose-dependent fashion. Over 75% and 95% of TrxR activity was lost at the dose of 250 mg/kg. There was, however, a recovery of TrxR activity such that it attained normal levels by 120 h after a dose of 250 mg/kg. In addition, we found that CTX caused a preferential TrxR inhibition over other antioxidant enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase. We also used ascites H22 cells to investigate cancer cells response after TrxR was inhibited by CTX
in vivo since CTX is needed to be activated by liver cytochrome P450 enzymes. The time course and dose-dependent changes of cellular TrxR activity were similar with those in tumor tissue. CTX caused a dose-dependent cellular proliferation inhibition which was positively correlated with TrxR inhibition at 3 h. Furthermore, when 3 h CTX-treated cells with various TrxR backgrounds, harvested from ascites-bearing mice, were implanted into mice, the proliferations of these cells were again proportionally dependent on TrxR activity. The TrxR inhibition could thereby be considered as a crucial mechanism contributing to anticancer effect seen upon clinical use of CTX.
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