Search

Abstract High-grade serous ovarian cancer (HGSOC) is an aggressive disease known to develop resistance to chemotherapy. We investigated the prognostic significance of tumor cell states and potential mechanisms underlying chemotherapy resistance in HGSOC. Transcriptome deconvolution was performed to address cellular heterogeneity. Kaplan–Meier survival curves were plotted to illustrate the outcomes of patients with varying cellular abundances. The association between gene expression and chemotherapy response was tested. After adjusting for surgery status and grading, several cell states exhibited a significant correlation with patient survival. Cell states can organize into carcinoma ecotypes (CE). CE9 and CE10 were proinflammatory, characterized by higher immunoreactivity, and were associated with favorable survival outcomes. Ratios of cell states and ecotypes had better prognostic abilities than a single cell state or ecotype. A total of 1265 differentially expressed genes were identified between samples with high and low levels of C9 or CE10. These genes were partitioned into three co-expressed modules, which were associated with tumor cells and immune cells. Pogz was identified to be linked with immune cell genes and the chemotherapy response of paclitaxel. Collectively, the survival of HGSOC patients is correlated with specific cell states and ecotypes.

Sepsis, a systemic inflammatory response caused by infection, can lead to sepsis-associated encephalopathy (SAE), characterized by brain dysfunction without direct central nervous system infection. The pathogenesis of SAE involves blood-brain barrier disruption, neuroinflammation and neuronal death, with neuroinflammation being the core process. Nogo-A, a neurite growth-inhibitory protein in the central nervous system, is not well understood in sepsis. This study explores Nogo-A's mechanisms in sepsis, focusing on SAE. Using in vivo and in vitro methods, healthy SPF C57BL/6J male mice were divided into Sham, Nogo-A-NC-Model, and Nogo-A-KD-Model groups, with sepsis induced by abdominal ligation and puncture. Morris water maze tests assessed learning and memory, and brain tissues underwent hematoxylin-eosin (HE) staining, Nissl staining, and Western blot analysis. In vitro, Nogo-A gene knockdown models were constructed using BV-2 microglia cells to study inflammation and oxidative stress. Results showed Nogo-A expression affected learning and memory in septic mice, with knockdown reducing neuronal damage. Bioinformatics analysis suggested Nogo-A may activate reactive oxygen species (ROS) to inhibit p-SHP2, activating mitochondrial autophagy and promoting neuronal apoptosis. Western blot results confirmed that Nogo-A affects mitochondrial autophagy and neuronal survival by inhibiting SHP2 and activating ROS. Nogo-A's role in neuroinflammation and neuroprotection was emphasized, revealing its impact on endoplasmic reticulum (ER) stress, mitochondrial autophagy, and NLRP3 inflammasome activation. This study provides a theoretical basis for SAE treatment, suggesting further multi-gene and multi-pathway analyses and validation in clinical samples. Developing gene therapy and drug interventions targeting Nogo-A pathways will offer more effective treatment strategies.

Abstract Background Immune dysregulation is a feature of sepsis. However, a comprehensive analysis of the immune landscapes in septic patients has not been conducted. Objectives This study aims to explore the abundance ratios of immune cells in sepsis and investigate their clinical value. Methods Sepsis transcriptome data sets were downloaded from the NCBI GEO database. The immunedeconv R package was employed to analyze the abundance of immune cells in sepsis patients and calculate the ratios of different immune cell types. Differential analysis of immune cell ratios was performed using the t test. The Spearman rank correlation coefficient was utilized to find the relationships between immune cell abundance and pathways. The prognostic significance of immune cell ratios for patient survival probability was assessed using the log-rank test. In addition, differential gene expression was performed using the limma package, and gene co-expression analysis was executed using the WGCNA package. Results We found significant changes in immune cell ratios between sepsis patients and healthy controls. Some of these ratios were associated with 28-day survival. Certain pathways showed significant correlations with immune cell ratios. Notably, six immune cell ratios demonstrated discriminative ability for patients with systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis, with an Area Under the Curve (AUC) larger than 0.84. Patients with a high eosinophil/B.cell.memory ratio exhibited poor survival outcomes. A total of 774 differential genes were identified in sepsis patients with a high eosinophil/B.cell.memory ratio compared to those with a low ratio. These genes were organized into seven co-expression modules associated with relevant pathways, including interferon signaling, T-cell receptor signaling, and specific granule pathways. Conclusions Immune cell ratios eosinophil/B.cell.memory and NK.cell.activated/NK.cell.resting in sepsis patients can be utilized for disease subtyping, prognosis, and diagnosis. The proposed cell ratios may have higher prognostic values than the neutrophil-to-lymphocyte ratio (NLR).

Background: The deadly cardiovascular condition known as Stanford type A aortic dissection (TAAD) carries a high risk of morbidity and mortality. One important step in the pathophysiology of the condition is the influx of immune cells into the aorta media, which causes medial degeneration. The purpose of this work was to investigate the potential pathogenic significance of immune cell infiltration in TAAD and to test for associated biomarkers. Methods: The National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database provided the RNA sequencing microarray data (GSE153434, GPL20795, GSE52093). Immune cell infiltration abundance was predicted using ImmuCellAI. GEO2R was used to select differentially expressed genes (DEGs), which were then processed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Additionally, hub genes linked to immune infiltration were found using functional and pathway enrichment, least absolute shrinkage and selection operator (LASSO), weighted gene co-expression network analysis (WGCNA), and differential expression analysis. Lastly, hub genes were validated and assessed using receiver operating characteristic (ROC) curves in the microarray dataset GSE52093. The hub gene expression and its connection to immune infiltration in TAAD were confirmed using both animal models and clinic data. Results: We identified the most important connections between macrophages, T helper cell 17 (Th17), iTreg cells, B cells, natural killer cells and TAAD. And screened seven hub genes associated with immune cell infiltration: ABCG2, FAM20C, ELL2, MTHFD2, ANKRD6, GLRX, and CDCP1. The diagnostic model in TAAD diagnosis with the area under ROC (AUC) was 0.996, and the sensitivity was 99.21%, the specificity was 98.67%, which demonstrated a surprisingly strong diagnostic power of TAAD in the validation datasets. The expression pattern of four hub DEGs (ABCG2, FAM20C, MTHFD2, CDCP1) in clinic samples and animal models matched bioinformatics analysis, and ABCG2, FAM20C, MTHFD2 up-regulation, and the of CDCP1 down-regulation were also linked to poor cardiovascular function. Conclusions: This study developed and verified an effective diagnostic model linked to immune infiltration in TAAD, providing new approaches to studying the potential pathogenesis of TAAD and discovering new medication intervention targets.

Abstract Introduction Ventricular septal defect (VSD) is a mechanical complication of acute myocardial infarction (MI) with a very high mortality, despite advances in surgical and circulatory support. The tremendous hemodynamic disturbance and the severely fragile myocardium render surgical repair a great challenge. The optimal time of surgical repair with or without circulatory support is still controversial. Objective The aim of this study is to review our experience with early surgical repair of post-MI VSD in a single major cardiac institution in China. Methods From January 2013 to October 2020, 9consecutive patients presented to our emergency department with a diagnosis of post-MI VSD. Among them, 8 were male, and the mean age was 58 ± 7years. The mean VSD size was 22.5 ± 5.7 mm. In all patients, an intra-aortic balloon pump (IABP)was inserted immediately after admission to cardiac surgery service. All patients were operated at a mean of 3.3 ± 2.9 days, and 4 within 24 h of the rupture (range 1 to 9 days post-VSD). In 5 cases, the VSD was located superiorly, and 4 cases in the posterior septum. Results The overall 30-day mortality was 11% (1/9). Coronary angiography was performed in all nine patients, four with single vessel disease had coronary stents implanted, and the other five received concomitant coronary artery bypass grafting during VSD repair surgery. There was no death in all 5 patients with anterior septal perforation. One patient with posterior septal perforation died in the operating room due to bleeding from the ventriculotomy site. Three survived patients were diagnosed with a small residual defect and mild left to right shunt post-repair. However, no further intervention was required, and patients remained asymptomatic (Killip II in 1 and III in 2). Conclusion In our experience, immediate insertion of IABP and hemodynamic stabilization with early surgical intervention of VSD repair and concomitant coronary revascularization provided an 89% survival rate.

Summary: The phosphoinositide 3-kinase p110α is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate p110α at T1061, which inhibits its activity. This inhibitory state corresponds to a conformational change of a membrane-binding domain on p110α, which impairs its ability to engage membranes. In human primary hepatocytes, cancer cell lines, and rodent tissues, activation of the Hippo kinases MST1/2 using forskolin or epinephrine is associated with phosphorylation of T1061 and inhibition of p110α, impairment of downstream insulin signaling, and suppression of glycolysis and glycogen synthesis. These changes are abrogated when MST1/2 are genetically deleted or inhibited with small molecules or if the T1061 is mutated to alanine. Our study defines an inhibitory pathway of PI3K signaling and a link between epinephrine and insulin signaling.

A mid-infrared (MIR) focusing grating coupler (FGC) with a single circular arc element (CAE) in the front of the gratings based on a germanium-on-silicon (Ge-on-Si) platform is designed and demonstrated. It can be used equivalently to a traditional FGC with all-focusing gratings. By optimizing the structural parameters of the CAE, the combination of a tapered linear grating and the CAE can improve the coupling efficiency to 8.61%, which is twice as large as that of the traditional MIR grating couplers. To the best of our knowledge, it is the highest coupling efficiency in a full-etch grating coupler based on Ge-on-Si. Moreover, the proposed grating coupler can be used for refractive index (RI) sensing, and the maximum sensitivity is 980.7 nm/RIU when the RI changes from 1 to 1.04. By comparing with traditional grating couplers requiring secondary etching, the proposed full-etch grating coupler structure can reduce the complexity of fabrication and can provide a prospective platform for MIR photonic integration and photonic biosensor detection.

To describe the changes of juicy peach microstructure under different drying methods, microstructure images and cell parameter distribution curves of juicy peach under different moisture ratios were obtained by using paraffin section, micro-imaging and image processing technologies, after treated by five drying methods (i.e. hot-air drying (HAD), vacuum drying (VD), freeze drying (FD), hot-air and vacuum combined drying (HA-VD), freeze and hot-air combined drying (F-HAD)). The effect of drying methods on microstructure parameters (i.e., cell area, cell perimeter, cell roundness, cell wall surface roughness and porosity) were analyzed via cell parameters distribution curves. Fitting equations were built by polynomial fitting to describe the correlation between cell parameters and moisture ratios. The results showed that microstructural parameters of juicy peach primarily changed in the first half process (moisture ratio>0.5) of hot air drying and second half process (moisture ratio

2,6-di-tert-butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di-tert-butyl-4-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol), would relieve the neuropathic phenotype that results from peripheral nerve damage, and that the anti-hyperalgesic efficacy in vivo would correlate with HCN1 channel inhibition in vitro. A single oral dose of probucol (800 mg/kg) relieved mechanical allodynia and thermal hyperalgesia in a mouse spared-nerve injury neuropathic pain model. While the low aqueous solubility of probucol precluded assessment of its possible interaction with HCN1 channels, our results, in conjunction with recent data demonstrating that probucol reduces lipopolysaccharide-induced mechanical allodynia and thermal hyperalgesia, support the testing/development of probucol as a non-opioid, oral antihyperalgesic albeit one of unknown mechanistic action.

ABSTRACT Enterococcus faecalis is a normal commensal of the human gastrointestinal tract (GIT). However, upon disruption of gut homeostasis, this nonmotile bacterium can egress from its natural niche and spread to distal organs. While this translocation process can lead to life-threatening systemic infections, the underlying mechanisms remain largely unexplored. Our prior work showed that E. faecalis migration across diverse surfaces requires the formation of matrix-covered multicellular aggregates and the synthesis of exopolysaccharides, but how enterococcal cells are reprogrammed during this process is unknown. Whether surface penetration endows E. faecalis with adaptive advantages is also uncertain. Here, we report that surface penetration promotes the generation of a metabolically and phenotypically distinct E. faecalis population with an enhanced capacity to endure various forms of extracellular stress. Surface-invading enterococci demonstrated major ultrastructural alterations in their cell envelope characterized by increased membrane glycolipid content. These changes were accompanied by marked induction of specific transcriptional programs enhancing cell envelope biogenesis and glycolipid metabolism. Notably, the surface-invading population demonstrated superior tolerance to membrane-damaging antimicrobials, including daptomycin and β-defensins produced by epithelial cells. Genetic mutations impairing glycolipid biosynthesis sensitized E. faecalis to envelope stressors and reduced the ability of this bacterium to penetrate semisolid surfaces and translocate through human intestinal epithelial cell monolayers. Our study reveals that surface penetration induces distinct transcriptional, metabolic, and ultrastructural changes that equip E. faecalis with enhanced capacity to resist external stressors and thrive in its surrounding environment. IMPORTANCE Enterococcus faecalis inhabits the GIT of multiple organisms, where its establishment could be mediated by the formation of biofilm-like aggregates. In susceptible individuals, this bacterium can overgrow and breach intestinal barriers, a process that may lead to lethal systemic infections. While the formation of multicellular aggregates promotes E. faecalis migration across surfaces, little is known about the metabolic and physiological states of the enterococci encased in these surface-penetrating structures. The present study reveals that E. faecalis cells capable of migrating through semisolid surfaces genetically reprogram their metabolism toward increased cell envelope and glycolipid biogenesis, which confers superior tolerance to membrane-damaging agents. E. faecalis’s success as a pathobiont depends on its antimicrobial resistance, as well as on its rapid adaptability to overcome multiple environmental challenges. Thus, targeting adaptive genetic and/or metabolic pathways induced during E. faecalis surface penetration may be useful to better confront infections by this bacterium in the clinic.

Abstract Background Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown. Methods Anticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-Catenin and its target genes were characterized by western blot and Real-time PCR. Results BZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-Catenin signaling pathway compared to monotherapy. Conclusions This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-Catenin signaling pathway in prostate cancer cells.

Glioblastoma patients are treated with Aurora kinase A (AURKA) inhibitors but resistance can occur. Here, the authors show that AURKA inhibition induces metabolic reprogramming, which leads to increased mitochondrial activity and inhibition of oxidative metabolism sensitizes glioblastoma cells to AURKA inhibition.

Summary: The coronavirus disease-19 (COVID-19) pandemic has ravaged global healthcare with previously unseen levels of morbidity and mortality. In this study, we performed large-scale integrative multi-omics analyses of serum obtained from COVID-19 patients with the goal of uncovering novel pathogenic complexities of this disease and identifying molecular signatures that predict clinical outcomes. We assembled a network of protein-metabolite interactions through targeted metabolomic and proteomic profiling in 330 COVID-19 patients compared to 97 non-COVID, hospitalized controls. Our network identified distinct protein-metabolite cross talk related to immune modulation, energy and nucleotide metabolism, vascular homeostasis, and collagen catabolism. Additionally, our data linked multiple proteins and metabolites to clinical indices associated with long-term mortality and morbidity. Finally, we developed a novel composite outcome measure for COVID-19 disease severity based on metabolomics data. The model predicts severe disease with a concordance index of around 0.69, and shows high predictive power of 0.83–0.93 in two independent datasets.

Abstract As a multi hop self-organizing network, wireless sensor network has the ability to cooperatively sense, collect and process the information of the sensed objects. The applications of WCN in 5G-based Internet of Vehicles (5G-IoV), using information fusion and intelligent information processing technologies, can obtain more reliable and accurate detection parameters, which has been widely concerned. However, the massive connectivity and information exchange in 5G-IoV pose great challenges to the bandwidth efficiency. In order to overcome these issues in 5G-IoV networks, a performance enhanced scheme based on non-orthogonal multiple access (NOMA) is proposed. In the proposed scheme, different vehicle locations are respectively discussed, i.e., whether in the overlap region of cluster head vehicles (CHVs). In particular, different to conventional works, each receiving node only decodes the desired signal to avoid performance loss provided from the poor channel quality limitation. On the other hand, all CHVs decode-and-forward new superposition coded signals with new power allocation factors, while that the maximum ratio combining is utilized at receivers to further improve the ergodic sum-rate (SR) and probability of conflict. The closed-form expressions of ergodic SR for our proposed scheme are analyzed under the independent Rayleigh fading channels. Numerical results corroborating our theoretical analysis show that the superposition coded signal transmission scheme applied to the proposed NOMA-IoV improves the ergodic SR performance significantly compared with the existing works, especially for the high signal-to-noise region.

A microfiber Mach-Zehnder interferometer (MMZI) with two spindle-shaped structures was reported for measuring temperature and curvature. Due to the core-separated structure, the MMZI could excite more high-order modes, which improves the sensitivity more efficiently. When the central waist region is 4 μm, the sensitivities for temperature and curvature were 1290.4pm /°C and 56.1947 nm/m−1, respectively. Furthermore, the sensitivity could be improved effectively by increasing the length of the central waist region. Increasing the length of central waist region to 6 μm, the temperature sensitivity of the sensor could up to 1756.3 pm/°C, which was the highest temperature sensitivity we have known in MMZI.

Summary: Autophagy is a conserved biological process that maintains cell homeostasis by targeting macromolecules for lysosome-mediated degradation. The levels of autophagy are relatively lower under normal conditions than under stress conditions (e.g., starvation), as autophagy is usually stimulated after multiple stresses. However, many autophagy-related regulators are still expressed under normal conditions. Although these regulators have been studied deeply in autophagy regulation, the nonautophagic roles of these regulators under normal conditions remain incompletely understood. Here, we found that autophagy-related 5 (ATG5), which is a key regulator of autophagy, regulates c-Myc protein degradation under normal conditions through the ubiquitin-proteasome pathway. We also found that ATG5 binds c-Myc and recruits the E3 ubiquitin-protein ligase FBW7 to promote c-Myc degradation. Moreover, ATG5-mediated degradation of c-Myc limits cell growth under normal conditions and is essential for embryonic stem cell differentiation. Therefore, this study reveals a nonautophagic role of ATG5 in regulating of c-Myc protein degradation.

Summary: Histones are the main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. Here, we describe detailed protocols for histone H2B purification from bacteria and for the separation of nucleolar fractions and cytoplasmic and nucleoplasmic fractions. Finally, the in vitro ubiquitination and degradation of H2B by distinct cellular fractions are described.For complete details on the use and execution of this protocol, please refer to Liu et al. (2021).

Elevated protein synthesis, and dysregulated mGluR signalling, are documented in fragile X syndrome (FXS) Here the authors use proteomic analysis in a mouse model of FXS, and following mGluR5 stimulation, to identify potential biomarkers for the disease.

Abstract In this paper, a receiver scheme for a cooperative multi-relay system with non-orthogonal multiple access (CMRS-NOMA) in cellular networks is proposed. In our proposed system, the base station (BS) would like to communicate with multiple users via multiple relays, and direct links between the BS and users are not considered. Specifically, we assume that the relays in the approaching range are allowed to assist the transmission since other relays are out of the cooperation range. In this way, each user and the corresponding relays can be implemented as one group. In addition, the source simultaneously transmits the superposition coded signals to all relay nodes. After receiving the signals, all the relay nodes decode the symbols by applying successive interference cancellation (SIC) and then reconstruct them into new NOMA signals, which will be forwarded to the users and decoded in a linear combination way. Note that the proposed reconstructions at the relay nodes are practical and simple, which leads to an advantageous decoding for the receivers. Moreover, the closed-form expressions in terms of the sum rate (SR) and the outage performance of the system are derived. Qualitative numerical results corroborating our theoretical analysis show that the proposed scheme significantly improves the performance in terms of the SR and outage probability compared with the existing works.

Taking into account the wireless physical layer security in energy-constrained relaying systems,a secure resource allocation scheme was proposed under simultaneous wireless information and power transfer (SWIPT) protocol.The utility optimization problem was considered aiming to maximize the secrecy rate by jointly optimizing the power splitting (PS) ratio and the transmit powers under the constraint of the transmit powers of the nodes and the harvested energy of the relay.The objective problem,which is non-convex,was decoupled into two subproblems.One was to optimize the PS ratio,another was to optimize the transmit powers.The optimal solution of the subproblems can be obtained in the closed-form.Then,the suboptimal solution is obtained with the proposed convergent iterative algorithm.Simulation results show the effects of artificial noise signal,residual self-interference signal,transmit power of nodes,amplification factor of relay and other factors on the security performance.Compared with the traditional gradient descent algorithm,the proposed algorithm can reduce more than 80% of the computational load,while the algorithm has the slightly better performance.

This paper investigates an effective resource utilization scheme for the decode-and-forward (DF) cooperative relaying networks (CRNs) with non-orthogonal multiple access (NOMA). Considering a T time slots transmission, the proposed effective resource utilization scheme adopts max-min relay selections to satisfy the quality-of-service (QoS) and provide a higher priority. Unlike the conventional CRNs, to improve the system performance and resource utilization, the unselected relays will continue receiving the signals transmitted by the base station (BS), as well as the selected relays forward the decoded signals to the user equipment (UE). Moreover, the maximum ratio combining (MRC) is utilized at the UE to jointly detect the receptions for each time slot. The achievable average sum-rate (SR) of the proposed system is analyzed for independent Rayleigh fading channels, and the asymptotic expressions are also provided. The qualitative numerical results corroborating our theoretical analysis show that the proposed effective resource utilization scheme significantly improves the transmission rate and SR performance in comparison to the conventional CRN-NOMA schemes.

A variable magnification ratio transmission structure powered by the electric actuators is proposed to improve the flexibility and portability of the exoskeleton under heavy load carrying condition. The parameters of connecting rod size and hanging position are optimized to ensure that the output torque of active joints can fully envelope the demand load area. The control strategy based on intrinsic sensing is designed to realize the automatic human motion intention prediction and flexible trajectory tracking. The newly developed split embedded connecting rod can accurately measure the human-robot interaction (HRI) force applied to the exoskeleton and extract the human motion intention without being affected by the differences in wearing status. The force tracking control based on the zero-force following is modified by feedforward compensation with extreme learning machine (ELM), which enhances the response speed to human motion intention and reduces the HRI force by 70.6%. Based on multi-sensor information, stacked autoencoder deep neural networks (DNNs) are utilized to realize the automatic locomotion transition and the corresponding control parameters' switching. After optimization by a hybrid algorithm of genetic algorithm and particle swarm optimization (GA_PSO), the identification accuracy is enhanced from 96.2% to 99.7%. The adaptive neural-fuzzy inference system (ANFIS) is used to analyze the plantar pressure to achieve flexible switching between the swing phase and the stance phase. The experiments under various gait motion trajectories assisted by novel weight-bearing exoskeleton are carried out for evaluation, and the performance of the proposed control strategy based on motion intention prediction, locomotion mode identification, and gait phase switching is effectively verified.

This paper focuses on an effective resource utilization scheme for the cooperative relay selection (RS) system with non-orthogonal multiple access (NOMA). In this work, an opportunistic suboptimal RS strategy is proposed that considers both of the users; as well as compared with the balanced and random RS schemes. For the proposed effective resource utilization scheme, the relay nodes are selected by incorporating a max-min selection manner to satisfy the quality of service (QoS) of the users; as well as the unselected relays continue receiving the signals transmitted from the base station (BS) for opportunities. In the meanwhile, the selected relay decodes the received superposed signals by employing the successive interference cancellation (SIC), and then reconstructs them into new NOMA signals, which will be forwarded to the users. Moreover, the closed-form expressions in terms of the sum rate (SR) and outage probability of the proposed transmission scheme are derived for independent Rayleigh fading channels. The provided simulation results show that the cooperative NOMA with the proposed effective RS scheme outperforms the existing works, and can also yield a significant performance gain over the orthogonal multiple access (OMA) scheme.

A tunable dual-wavelength with two separated twin-pulse dissipative solitons (DSs) of Yb-doped mode-locked fiber laser in the all-normal-dispersion (ANDi) regime is firstly reported and demonstrated in this paper. A Sagnac loop is used as an all-fiber format spectral filter in the laser cavity, and stable twin-pulse DSs with different wavelength mode-locked lasers are achieved by the nonlinear polarization evolution (NPE) effect. By adjusting the polarization state of the Sagnac loop, the spectral ranges of the dual-wavelength can be tuned from 1031.3 nm to 1041.5 nm and from 1067.1 nm to 1080.9 nm, respectively. However, the pulse space between the two separated twin-pulse DSs is maintained, i.e., 41.63 ns. Furthermore, the twin-pulse can regress to the single-pulse when the pump power keeps dropping. It has been observed that the highest energy of the two twin-pulse DSs output is 23.36 nJ at a repetition rate of 2.282 MHz with a maximum pump power of 560 mW.

Summary: Fascin protein is the main actin-bundling protein in filopodia and invadopodia, which are critical for tumor cell migration, invasion, and metastasis. Small-molecule fascin inhibitors block tumor invasion and metastasis and increase the overall survival of tumor-bearing mice. Here, we report a finding that fascin blockade additionally reinvigorates anti-tumor immune response in syngeneic mouse models of various cancers. Fascin protein levels are increased in conventional dendritic cells (cDCs) in the tumor microenvironment. Mechanistically, fascin inhibitor NP-G2-044 increases the number of intratumoral-activated cDCs and enhances the antigen uptake by cDCs. Furthermore, together with PD-1 blocking antibody, NP-G2-044 markedly increases the number of activated CD8+ T cells in the otherwise anti-PD-1 refractory tumors. Reduction of fascin levels in cDCs, but not fascin gene knockout in tumor cells, mimics the anti-tumor immune effect of NP-G2-044. These data demonstrate that fascin inhibitor NP-G2-044 simultaneously limits tumor metastasis and reinvigorates anti-tumor immune responses.

Alternol is a naturally occurring compound that exerts antitumor activity in several cancers. However, whether Alternol induces antitumor immune response remains unknown. In this study, we investigated whether Alternol induced immunogenic cell death (ICD) in prostate cancer cells. Alternol triggered ICD in prostate cancer cells, as evidenced by the release of damage-associated molecular patterns (DAMPs) (i.e., calreticulin, CALR; high mobility group protein B1, HMGB1; and adenosine triphosphate, ATP) and pro-inflammatory cytokine (i.e., interleukin [IL]-1α, IL-1β, IL-6, and IL-8) expression. Alternol facilitated tumor-associated antigen uptake and cross-presentation, CD8 + T-cell priming, and T-cell infiltration in tumor-draining lymph nodes (LNs) and tumors. The presence of Alternol fostered antitumor immune response in vivo, resulting in delayed tumor growth and prolonged survival. Moreover, inhibition of reactive oxygen species (ROS) generation blocked Alternol-induced upregulation of pre-inflammation cytokines, endoplasmic reticulum (ER) stress, and consequent antitumor immune response. Overall, our data indicate that Alternol triggers ICD in prostate cancer cells, which is mediated by ROS generation.

Abstract Background Genetic polymorphisms at 23 short tandem repeat (STR) loci were investigated in 1,215 Jining Han individuals from Jining city, Shandong province, eastern China. Methods We used population genetic data of 23 autosomal STR loci included in the Huaxia Platinum system to evaluate 1,215 unrelated Chinese Han individuals in the Jining Han population. Allele frequencies and forensic parameters of the STR loci were determined and genetic relationships among the Jining Han and other Chinese populations were evaluated. Results In total, we observed 321 alleles, with frequencies ranging from 0.00041 to 0.52222. The combined discrimination power and probability of excluding paternity were 0.99999999999999999999999999919 and 0.99999999962, respectively. No deviations from HWE were observed at any loci. Population comparisons showed that the Xinjiang groups (Uyghur and Kazakh) and the Mongolian and Tibetan groups were isolated, while the Jining Han population clustered together with other populations, except the Guizhou Han population. Conclusion This study demonstrated that 23 autosomal STR loci included in the Huaxia Platinum system are highly polymorphic and suitable for personal forensic identification and paternity testing in this population.

Abstract Background Malignant tissue samples may be the only source of biological material for forensic investigations, including individual identification or paternity testing; however, such samples may lead to uncertainties due to frequent genomic aberrations associated with tumors, including alterations of the short tandem repeat (STR) loci used for forensic casework. Methods Short tandem repeat loci routinely used in forensic analysis (n = 23) were analyzed in 68 surgically removed papillary thyroid cancer specimens. Tumor cells and normal stromal cells were separated by laser capture microdissection. Results Four kinds of changes were detected between normal and tumor tissues: partial loss of heterozygosity (pLOH), complete loss of heterozygosity, an additional allele, and a new allele not found in normal tissue. These changes were distributed across 20 of the tested STRs, with no mutations in VWA, D16S539, or Penta D. The most frequently affected locus was D2S1338, and the most frequent type of alteration was pLOH. Samples from patients aged 40–59 years exhibited the highest frequencies of STR variation. Conclusion Our results suggest that great care should be taken in the evaluation of DNA typing results obtained from malignant tissues, particularly when no normal tissue reference samples are available.

Abstract In this paper, an enhanced transmission scheme for cooperative relaying networks with non-orthogonal multiple access (ECRN-NOMA) is proposed. In the proposed scheme, two different kinds of transmission schemes are investigated which are the single signal transmission and the enhanced superposition transmission schemes. Particularly, for the single transmission scheme, a successive interference cancellation (SIC) is utilized to decode the received signal, sent by the relay, at the destination. On the other hand, for the enhanced superposition coded signal transmission scheme, a maximum ratio combining (MRC) is utilized at the destination to improve the ergodic sum-rate (SR) of the proposed system. Specifically, two power allocation (PA) strategies are comprehensively discussed to characterize the performance of our proposed scheme. The achievable average SR of the proposed systems are analyzed for independent Rayleigh fading channels, and also their asymptotic expressions are also provided. Qualitative numerical results corroborating our theoretical analysis show that the enhanced superposition coded signal transmission scheme applied to the proposed ECRN-NOMA improves the SR performance significantly in comparison to the others.

Abstract This paper investigates decoupled beamforming techniques for the distributed multi-input multi-output (MIMO) two-way relay networks (TWRN) with imperfect channel state informations (CSIs). The objective of this paper is to maximize the weighted sum rate (SR) with semi-infinite relay power constraints. Since the objective problem is difficult to be solved directly, considering the high signal-to-residual-interference-plus-noise ratio (SRINR) and employing the Cauchy-Schwarz inequality and S-lemma, the problem can be approximately converted into a source beamforming decoupled one. In addition, with the optimal relay beamforming design and maximum ratio combining (MRC) at the receiver, the MIMO channels are decoupled into parallel single-input single-output (SISO) channels. By this way, the suboptimal relay beamforming matrix can be efficiently obtained with minimal relay power constraint. Specifically, the semi-infinite constraints can be reformulated into a linear matrix inequality (LMI), which can be efficiently solved by using an alternating optimization algorithm. Numerical results demonstrate that our proposed decoupled beamforming scheme outperforms the existing works in terms of the SR and the computational complexity with satisfactory convergence.

A beamforming design was proposed under simultaneous wireless information and power transfer (SWIPT) protocol.A utility optimization problem was considered aiming to maximize the harvested energy by jointly optimizing the beamforming matrix,the power splitting ratio at the relay and the transmit powers at the sources.Since the formulated joint optimization problem was nonconvex,it was difficult or even intractable to obtain the global optimal solution.To overcome this issue,the objective problem into three subproblems was decoupled which could be solved by the proposed semidefinite relaxation technique and the derived constraints activation solution,respectively.The solution was finally obtained with the proposed convergent iterative algorithm.Simulation results show that the proposed joint optimization scheme achieves the optimal performance.Compared with the traditional half-duplex (HD) algorithm,the proposed algorithm can obtain 2~3 times energy harvesting (EH) efficiency improvement,while the computational complexity increases slightly.

In this paper, a two-stage superposed transmission scheme for cooperative nonorthogonal multiple access (NOMA) systems is proposed. During the first N time slots, the source simultaneously transmits the superposition coded symbols to the relay and destination, both of which, instead of decoding, keep the receptions in reserve. At the last time slot, the relay decodes and forwards a new superposition coded symbol with corresponding power allocation factors to the destination. The destination jointly decodes the received signals during the total N + 1 time slots by employing maximum ratio combining. Assuming Rayleigh fading channels, the ergodic sum rate (SR), outage probability, and outage capacity of the system are investigated considering the high transmit signal-to-noise ratio cases. An approximate expression for the ergodic SR is also derived at the expense of a negligible performance loss. By means of numerical results, it is shown that the transmission rate and ergodic SR of the proposed scheme overwhelm that of the time-division multiple access and conventional NOMA schemes.

Summary: Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis. : In a human neural stem cell model of low-grade astrocytoma, Modrek et al. show that mutant IDH1 and loss of P53 and ATRX together block differentiation via disassociation of SOX2 from putative enhancers. This occurs because of disruption of chromatin looping secondary to hypermethylation at CTCF motifs. Keywords: low-grade glioma, astrocytoma, IDH, P53, ATRX, neural stem cells, SOX2, chromatin looping, CTCF, DNA methylation

In order to solve the problem of the communication performance of degradation,which caused by multi-intersections in city environment and no sensitivity to individual node movements,an intersection-based geographical perception routing protocol in vehicular Ad Hoc network was proposed.The network gateways select road intersections to form the backbone of the route,ensuring a high probability of communication and meeting delay and bit error rate requirements.Mathematical formula of the average delay and the average number of hops were obtained on the basis of a two-way road model.Simulation results show that the transmission delay of IGPR is smaller,the number of hops of IGPR is less,and the communication performance of IGPR is better compared with the FRGR protocols and VRR protocols.

This paper studies simultaneous wireless information and power transfer in full-duplex (FD) two-way relay networks, where two energy-constrained sources are served by a FD multi-antenna powersupply relay. Using FD technique at the relay can cause self-interference (SI) for the signal forwarding, but this SI can be useful for energy harvesting at two sources. To reasonably compress and utilize the SI, we consider a utility optimization problem aiming to maximize the total harvested energy by jointly optimizing the transmit power, the power splitting ratio at the sources and the beamforming matrix at the relay. In specific, we consider two relaying protocols, amplify-and-forward and decode-and-forward. To solve the complex non-convex problem, we decouple the objective problem into two subproblems which can be solved by the proposed semidefinite relaxation technique and the derived constraints activation solution. We show that the optimal solution of certain subproblems can be obtained in the closed-form. By this way, the objective problem can be finally tackled by utilizing a convergence guaranteed alternating optimization algorithm. Numerical results show that the proposed FD scheme achieves significant improvement of the energy harvesting efficiency compared with the existing works with different transmission protocols, i.e., half-duplex, perfect FD, and non-joint FD.

This paper studies the beamforming designs for simultaneous wireless information and power transfer systems in two-way relaying (TWR) channels. The system consists of two energy-constrained source nodes which employ the power splitting (PS) to receive the information and the energy simultaneously from the power-supply relay. To maximize the weighted sum energy subject to the constraints of the quality of service and the transmit powers, three well-known relaying protocols, i.e., amplify-and-forward, bit level XOR-based decode-and-forward (DF), and symbol level superposition coding-based DF, are considered. For each relaying protocol, we formulate the joint relay beamforming, the source transmit power, and the PS ratios optimization as a nonconvex quadratically constrained problem. To solve the complex nonconvex problem, we decouple the objective problem into two subproblems in which one is to optimize the beamforming vectors while another is to optimize the remaining parameters. We show that the optimal solution of each subproblem can be obtained in the closed-form expressions. The solution is finally obtained with the proposed convergent iterative algorithm. Extensive numerical results demonstrate the advantage of adapting the different relaying strategies and weighted factors to harvest energy in TWR channels.

A reliability routing protocol based on vehicle density in vehicular Ad Hoc network was proposed to reduce the complexity of finding an optimal or sub-optimal node of the forwarding node in forwarding range,reducing the average number of hops and enhancing the reliability of the link.Firstly,the size of the unite block was set by the forwarding node according to the vehicle density in the road.And the forwarding range was cut into several equal blocks.Then the farthest block away from the forwarding node was selected.In the selected block,the neighbor node which had the longest link time was chosen as a relay node to forward according to the principle of reliability finally.Compared with EG-RAODV,the simulated results of the proposed routing protocol show that the average number of hops is less and the average distance of one-hop progress is lager,which means the proposed routing protocol can transmit the data packet to destination node more quickly.

Considering the cognitive channel access problem of vehicle nodes in cognitive vehicular networks with heavy traffic environment,a channel access algorithm called clusters-UCB which based on clusters and MAB model was proposed.The cooperation of cluster members could improve perception accuracy and enhance the learning speed.And using improved multi-user UCB algorithm,cluster heads could quickly search out the optimal channel in a distributed way,which could make the network asymptotically achieve the optimal slot throughput.Simulation results show that with respect to UCB algorithm and ε-greedy algorithm,the regret of the proposed algorithm is lower and the speed of approaching logarithmic form is faster.What's more,clusters-UCB can effectively reduce the number of collisions when clusters access the cognitive channels,ensuring the fairness of the channel access and achieving better slot throughput.

In vehicle-to-infrastructure (V2I) communications, various failures in the dynamic movement pose serious link interruptions. To study the continuous service quality for the V2I network when this issue happens, this paper proposes a survivability analysis and establishes the communication architecture for software-defined network (SDN)-based V2I communications. With the controllable advantages of SDN centralized management, the multi-path transmission control protocol is used to seamlessly switch the transmission information between the V2I links of each vehicle node. Specifically, according to the analysis of specific fault types for V2I links, the definitions of SDN-based V2I survivability is provided to establish the corresponding survivability mode. To further verify the survivability model, a full-state search is adopted by means of probability model checker PRISM. In addition, multi-directional probability and expected reward evaluation analyses are carried out from the point of view of time. The simulation results show that, with the failure of multiple V2I links, the network quality of service (QoS) correspondingly declines, but the network still survives, due to the multi-path transmission control protocol (MPTCP) action. Moreover, with a high fault repair rate, the service performance and survivability of the network is improved rapidly.

Mobile-edge computation offloading (MECO) is a promising emerging technology for battery savings in mobile devices (MD) and/or in latency reduction in the execution of applications by (either total or partial) offloading highly demanding applications from MDs to nearby servers such as base stations. In this paper, we provide an offloading strategy for the joint optimization of the communication and computational resources by considering the blue trade-off between energy consumption and latency. The strategy is formulated as the solution to an optimization problem that minimizes the total energy consumption while satisfying the execution delay limit (or deadline). In the solution, the optimal transmission power and rate and the optimal fraction of the task to be offloaded are analytically derived to meet the optimization objective. We further establish the conditions under which the binary decisions (full-offloading and no offloading) are optimal. We also explore how such system parameters as the latency constraint, task complexity, and local computing power affect the offloading strategy. Finally, the simulation results demonstrate the behavior of the proposed strategy and verify its energy efficiency.

A modified binary partition assisted broadcast（MBPAB）protocol was proposed, which was designed for emergency messages dissemination in vehicular Ad Hoc network（VANET）. The protocol divided the communication range into small sectors, and sought the farthest possible nodes in the farthest sector from the sender node to be the forwarding node to increase the dissemination speed by reducing the forwarding hops. A mini distributed inter-frame space（mini-DIFS）in a medium access control（MAC）sublayer was introduced to give the emergency messages a higher access priority to the communication channel compared with other messages. The results demonstrate that MBPAB protocol outperforms benchmarks of the existing broadcast protocols in VANET in terms of communication delay and the average message dissemination speed.

OBJECTIVES: To provide a quantitative assessment of the association between excess body weight, interpreted as increased body mass index (BMI), and the risk of gallbladder cancer (GBC). METHODS: We identified eligible studies in Medline and EMBASE up to 1 February 2015, and reference lists of retrieved articles. Summary relative risks with their 95% confidence intervals were calculated in a random-effects model. Subgroup analyses were performed according to study design, gender, geographic location, ascertainment of exposure and adjustment for confounders. RESUITS: A total of 12 cohort studies and 8 case-control studies were included in the meta-analysis. Overall, compared with “normal” weight, the summary relative risks of GBC were 1.14 (95% CI, 1.04–1.25) for overweight individuals (BMI 25–30 kg/m2) and 1.56 (95% CI, 1.41–1.73) for obese individuals (BMI > 30 kg/m2). Obese women had a higher risk of GBC than men did (women: SRRs 1.67, 95% CI 1.38–2.02; men: SRRs 1.42, 95% CI 1.21–1.66), and there was significant association between overweight and GBC risk in women (SRRs 1.26, 95% CI 1.13–1.40), but not in men (SRRs 1.06, 95% CI 0.94–1.20). CONCLUSIONS: Findings from this meta-analysis indicate that obesity is associated with an increased risk of GBC, especially in women. Overweight is associated with GBC risk only in women.

In order to solve the problem of unstable connectivity and high bit error rate,which are caused by rapid changes in the density of vehicles on the road,while the transmission radius remained unchanged,a variable transmission range routing protocols based on vehicle density in vehicular Ad-Hoc network was proposed.According to different vehicle density,node could adjust the farthest transmission distance and reduce the transmission latency of the message,which could ensure high connection probability of the network.Based on homogeneous poisson point process model,the change conditions of transmission range with different vehicle density were deduced,and its feasible was proved.Furthermore,mathematical calculate formula of average latency was obtained according to the theoretical analysis.At last,variable transmission range routing protocol based on vehicle density and fixed transmission range routing protocol were compared by simulation.The simulated results show that the proposed protocol can be applied in actual environments,and the message can be transmitted fast from source node to destination node under the condition of high connection probability.

The passive exoskeleton with an automatic load-adapting mechanism is proposed in the article, which can assist people to do rehabilitation exercise and be used for the load carrying. The structure of the overall design is expounded in detail. In order to achieve a more efficient arrangement of space structure and to reduce the weight of the structure, a gas spring was selected as the passive energy actor. Furthermore, through effective design, the capability of automatic load-adapting was achieved in the structure. As the characteristics of the gas spring force will change with increasing elongation, curve fitting of the function to the gas spring force was achieved by the structural design. As a result, the performance of the exoskeleton was improved significantly after balancing.

Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2. Ligand-dependent Y504 phosphorylation modulates the EphB-NMDAR interaction in cortical and spinal cord neurons. Furthermore, Y504 phosphorylation enhances NMDAR localization and injury-induced pain behavior. By mediating inducible extracellular interactions that are capable of modulating animal behavior, extracellular tyrosine phosphorylation of EphBs may represent a previously unknown class of mechanism mediating protein interaction and function.

For the dynamic features of cognitive vehicular Ad Hoc network（CVANET）channel state, a study on spectrum sensing and access of cognitive vehicle users was presented, which was based on framework of partially observable Markov decision process（POMDP）. Then, a decentralized opportunity spectrum access based on POMDP model was proposed. Because there is a huge computational complexity, the greedy algorithm was sought. Finally, the influence factors of cognitive vehicle user throughput through the simulation were studied, and the feasibility of the algorithm was verified. The simulation results show that cognitive vehicle user's access throughput is effectively improved by this algorithm which avoid the happening of broadcast storm and also simplify the calculation.

An alarm message detection algorithm for the traffic accident based on linear cooperative strategy in vehicular Ad Hoc network was proposed, and it was composed of two parts: local detection and global detection. Cluster heads received the statistics of detection signal strength from local mobile vehicle node, and conducted global linear combination to make a final decision. The numerical simulation results show that the proposed strategy can improve the detection probability within the scope of the false alarm probability, and avoid the broadcast storm.