Tyramine-Invertase Bioconjugate-Amplified Personal Glucose Meter Signaling for Ultrasensitive Immunoassay.

Highly sensitive and facile detection of low levels of protein markers is of great significance for the early diagnosis and efficacy monitoring of diseases. Herein, aided by an efficient tyramine-signal amplification (TSA) mechanism, we wish to report a simple but ultrasensitive immunoassay with signal readout on a portable personal glucose meter (PGM). In this study, the bioconjugates of tyramine and invertase (Tyr-inv), which act as the critical bridge to convert and amplify the protein concentration information into glucose, are prepared following a click chemistry reaction. Then, in the presence of a target protein, the sandwich immunoreaction between the immobilized capture antibody, the target protein, and the horseradish peroxidase (HRP)-conjugated detection antibody is specifically performed in a 96-well microplate. Subsequently, the specifically loaded HRP-conjugated detection antibodies will catalyze the amplified deposition of a large number of Tyr-inv molecules onto adjacent proteins through highly efficient TSA. Then, the deposited invertase, whose dosage can faithfully reflect the original concentration of the target protein, can efficiently convert sucrose to glucose. The amount of finally produced glucose is simply quantified by the PGM, realizing the highly sensitive detection of trace protein markers such as the carcinoembryonic antigen and alpha fetoprotein antigen at the fg/mL level. This method is simple, cost-effective, and ultrasensitive without the requirement of sophisticated instruments or specialized laboratory equipment, which may provide a universal and promising technology for highly sensitive immunoassay for in vitro diagnosis of diseases.

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy.

Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. Exosomes can be derived from cancer cells as well as cellular components in tumor microenvironment. After secretion, the exosomes carrying a wide range of bioactive cargos can be ingested by local or distant recipient cells. The released cargos act through a variety of mechanisms to elicit multiple biological effects and impact most if not all hallmarks of cancer. Moreover, owing to their excellent biocompatibility and capability of being easily engineered or modified, exosomes are currently exploited as a promising platform for cancer targeted therapy. In this review, we first summarize the current knowledge of roles of exosomes in risk and etiology, initiation and progression of cancer, as well as their underlying molecular mechanisms. The aptamer-modified exosome as a promising platform for cancer targeted therapy is then briefly introduced. We also discuss the future directions for emerging roles of exosome in tumor biology and perspective of aptamer-modified exosomes in cancer therapy.

Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA.

Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.

Self-Assembled Pure Covalent Tubes Exhibiting Circularly Polarized Luminescence.

Here, we successfully synthesized four structurally analogous, self-assembled chiral molecular tubes with relatively high yields. This achievement involved the condensation of six equivalents of enantiomerically pure trans-cyclohexane-1,2-diamine (trans-CHDA) and three equivalents of the corresponding tetraformyl precursor. Each precursor was equipped with a luminescent linker terminated by two m-phthalaldehyde units. Even though these tetraformyl precursors are barely soluble in almost all organic solvents, the molecular tubes are highly soluble in nonpolar solvents such as chloroform, allowing us to fully characterize them in solution. The stereo-chirality of the chiral bisamino building blocks endows the frameworks of molecular tubes with planar chirality. As a consequence, all of these molecular tubes exhibit circularly polarized luminescence (CPL) with relatively large dissymmetry values |glum| up to 7×10-3, providing an efficient method for synthesizing CPL-active materials.

Exploring the correlation of metabolites changes and microbial succession in solid-state fermentation of Sichuan Sun-dried vinegar.

BACKGROUND: The traditional Sichuan Sun-dried vinegar (SSV) with unique flavor and taste is believed to be generated by the solid-state fermentation craft. However, how microorganisms and their metabolites change along with fermentation has not yet been explored. RESULTS: In this study, our results demonstrated that the middle and late stages of SSV fermentation were the periods showing the largest accumulation of organic acids and amino acids. Furthermore, in the bacterial community, the highest average relative abundance was Lactobacillus (ranging from 37.55 to 92.50%) in all fermentation stages, while Acetobacters ranked second position (ranging from 20.15 to 0.55%). The number of culturable lactic acid bacteria is also increased during fermentation process (ranging from 3.93 to 8.31 CFU/g). In fungal community, Alternaria (29.42%), Issatchenkia (37.56%) and Zygosaccharomyces (69.24%) were most abundant in different fermentation stages, respectively. Interestingly, Zygosaccharomyces, Schwanniomyces and Issatchenkia were first noticed as the dominant yeast genera in vinegar fermentation process. Additionally, spearman correlation coefficients exhibited that Lactobacillus, Zygosaccharomyces and Schwanniomyces were significant correlation with most metabolites during the fermentation, implying that these microorganisms might make a significant contribution to the flavor formation of SSV. CONCLUSION: The unique flavor of SSV is mainly produced by the core microorganisms (Lactobacillus, Zygosaccharomyces and Schwanniomyces) during fermentation. This study will provide detailed information related to the structure of microorganism and correlation between changes in metabolites and microbial succession in SSV. And it will be very helpful for proposing a potential approach to monitor the traditional fermentation process.

Anti-Inflammatory and Anti-Osteoclastogenesis Activities of Different Kinds of Zanthoxylum bungeanum Seed Oil in Vitro.

Our previous study has exhibited that one kind of Zanthoxylum bungeanum seed oil (ZSO), extracted from Zanthoxylum bungeanum seed, had inhibitory effects on osteoclastogenesis. However, the anti-osteoclastogenesis activities of different kinds of ZSO are scarcely reported. Since inflammation is related to bone loss and osteoporosis, in this study, three kinds of ZSO, Zanthoxylum schinifolium Siebold et Zucc seed oil (ZSSO), Zanthoxylum armatum DC. seed oil (ZDSO) and Zanthoxylum bungeanum maximum seed oil (ZBSO), were obtained with Soxhlet extraction and their fatty acid constituents were detected by GC-FID. RAW264.7 macrophages induced by lipopolysaccharide (LPS) were used to evaluate the inhibitory effects of three kinds of ZSO on inflammation via detecting the expression levels of inflammatory factors by RT-qPCR. Moreover, RANKL-induced osteoclastogenesis was applied to demonstrate the anti-osteoclastogenesis activities of them through tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR. The GC-FID results exhibited that the highest constituent in ZSSO and ZDSO was oleic acid (OA) and palmitoleic acid (PLA), respectively. While linoleic acid (LA) and α-Linolenic acid (ALA) in ZBSO were dominant. At the concentration of 0.5 µL/mL, all three kinds of ZSO could decrease the expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) in LPS-induced macrophages. At the concentration of 0.25 µL/mL, only ZSSO could decrease the expression levels of iNOS and COX-2, which implied the inhibitory effects of ZSSO were stronger than other ZSOs. The number of RANKL-induced osteoclasts and the expressions of nuclear factor kappa-B (NF-κB), TNF-α and IL-6 in the cells were decreased after being treated with ZSOs at the concentration of 0.5 µL/mL, while the number of RANKL-induced osteoclasts after treated with ZBSO were less than those treated with other ZSOs, this indicated that the anti-osteoclastogenesis effect of ZBSO were stronger than other ZSOs. In conclusion, the fatty acid compositions of three major kinds of ZSO were compared and the content of unsaturated fatty acids especially ω-3 polyunsaturated fatty acids in ZBSO were the highest among them. All ZSOs tested had anti-inflammatory and anti-osteoclastogenesis activities. And their anti-osteoclastogenesis effects might be related to the suppression of the NF-κB pathway.

Identification and whole-genome sequencing analysis of Vibrio vulnificus strains causing pearl gentian grouper disease in China.

Vibrio vulnificus is a pathogenic bacterium that causes disease in marine fish, affecting fish farming and human health worldwide. In May 2021, in the Bohai Bay region, a disease broke out in commercially farmed pearl gentian grouper (♀Epinephelus fuscoguttatus × â™‚Epinephelus lanceolatus), causing huge economic losses. The diseased fish had skin lesions, water accumulation in their abdomens, and showed tissue and organ damage. V. vulnificus biotype 2 has been reported in eels and other marine fish, but it is less reported in pearl gentian grouper. In this study, the pathogenic strain isolated from diseased fish was identified as V. vulnificus EPL 0201 biotype 2 on the basis of physiological and biochemical characteristics and the results of 16S rRNA gene and gyrB sequencing, virulence gene detection, and recursive infection experiments. To gain a comprehensive understanding of the pathogenicity and drug resistance of this strain, whole-genome sequencing was performed. Whole-genome analysis showed that the gene map of this strain was complete. The Virulence Factor Database annotation results showed that this strain had the key virulence factor genes vvhA and rtxA, which cause host disease. In addition, this strain had genes conferring resistance against cephalosporins, aminoglycosides, tetracyclines, and sulfonamides. Antimicrobial susceptibility testing confirmed the presence of these resistance genes identified in the genome. The results of this study show that V. vulnificus EPL 0201 biotype 2 is a multi-drug resistant strain with high pathogenicity.

Genome-Wide Identification, Expression, and Interaction Analysis of BEL-Like Homeodomain Gene Family in Peach.

BEL1-like homeodomain (BLH) family genes as homeodomain transcription factors are found ubiquitously in plants to play important regulatory roles in reproductive development, morphological development, and stress response. Although BLH proteins have been reported in some species, there is little information about BLH genes in peach. In this study, we identified 11 peach PpBLH genes based on the conserved domain. Phylogenetic analysis suggested that the PpBLH proteins could be divided into five groups, which might be involved in different aspects of morphogenesis. Genomics structure analysis revealed that there were four exons in the PpBLH gene, and the length of the third exon was 61 bp. Chromosomal location analysis showed that the PpBLH genes were not distributed uniformly on six chromosomes. Promoter analysis showed that the promoter sequences of six PpBLH genes contained multiple cis-acting elements for hormones and stress. Six PpBLH genes were cloned by RT-PCR, and PpBLH1, PpBLH4, and PpBLH7 showed different expression patterns in the tested fruits under common temperature and high temperature. Y2H results indicated that PpBLH7 andPpBLH10 interacted with the PpOFP6 protein, and PpBLH1 interacted with the PpOFP1, PpOFP2, PpOFP4, and PpOFP13 proteins. These results provide new insight for further study of PpBLH genes, and construction of regulatory networks of PpBLH proteins in the growth, development, and stress response of peach.

Path Loss Model for 3.5 GHz and 5.6 GHz Bands in Cascaded Tunnel Environments.

An important and typical scenario of radio propagation in a railway or subway tunnel environment is the cascaded straight and curved tunnel. In this paper, we propose a joint path loss model for cascaded tunnels at 3.5 GHz and 5.6 GHz frequency bands. By combining the waveguide mode theory and the method of shooting and bouncing ray (SBR), it is found that the curvature of tunnels introduces an extra loss in the far-field region, which can be modeled as a linear function of the propagation distance of the signal in the curved tunnel. The channel of the cascaded straight and curved tunnel is thus characterized using the extra loss coefficient (ELC). Based on the ray-tracing (RT) method, an empirical formula between ELC and the radius of the curvature is provided for 3.5 GHz and 5.6 GHz, respectively. Finally, the accuracy of the proposed model is verified by measurement and simulation results. It is shown that the proposed model can predict path loss in cascaded tunnels with desirable accuracy and low complexity.

A Self-Assembled Cage Binding Iodide Anions over Other Halide Ions in Water.

A triangular-prism shaped cage was self-assembled by the formation of a dynamic covalent bond, namely a hydrazone, in acidic aqueous solution. The hexacationic host bears a number of relatively acidic protons pointing inside the cage cavity, which is able to accommodate an iodide anion selectively in water over other halide anions such as F- , Cl- , and Br- , which are more hydrated. As a comparison, a macrocycle analogue bearing fewer positive charges and fewer hydrogen bond donors shows no anion binding ability. As inferred from the single-crystal structure and theoretical calculations, the ability of the cage to selectively recognize iodide anions results from the combination of electrostatic forces, C-H⋅⋅⋅I- hydrogen bonds, and the hydrophobic effect.

[Neuropsychological development of human immunodeficiency virus-exposed uninfected infants/young children]. / äººç±»å ç–«ç¼ºé™·ç— æ¯’æš´éœ²æœªæ„ŸæŸ“å©´å¹¼å„¿çš„ç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µ.

OBJECTIVES: To investigate the level of neuropsychological development in human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants/young children and the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children. METHODS: A total of 141 HEU infants/young children, aged 0-18 months and born to HIV-infected mothers, who were managed in four maternal and child health care hospitals in Yunnan Province of China from June 2019 to December 2020 and met the inclusion criteria were enrolled as the HEU group. A total of 141 HIV-unexposed uninfected (HUU) infants/young children who were born to healthy mothers and managed in the same hospitals, matched at a ratio of 1:1 based on sex, age, method of birth, birth weight, and gestational age, were enrolled as controls. Griffiths Development Scales-Chinese Edition was used to assess the development in the five domains of locomotion, personal-social, hearing and language, eye-hand co-ordination, and performance (visual perception and space integration ability). A questionnaire survey was performed to collect relevant information. The multivariate logistic regression analysis was used to assess the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children. RESULTS: Compared with the HUU group, the HEU group had significantly higher detection rates of retardation in the domains of hearing and language and performance (P<0.05). The multivariate logistic regression analysis showed that maternal HIV infection increased the risk of retardation in the domains of hearing and language (OR=2.661, 95%CI: 1.171-6.047, P<0.05) and performance (OR=2.321, 95%CI: 1.156-4.658, P<0.05). CONCLUSIONS: Maternal HIV infection can negatively affect the development of hearing and language and performance in HEU infants/young children, and further studies are needed to clarify related mechanisms.

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious.

BACKGROUND: Previous studies showed that recovered coronavirus disease 2019 (COVID-19) patients can have a subsequent positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after they are discharged from the hospital. Understanding the epidemiological characteristics of recovered COVID-19 patients who have a re-positive test is vital for preventing a second wave of COVID-19. METHODS: This retrospective study analyzed the epidemiological and clinical features of 20,280 COVID-19 patients from multiple centers in Wuhan who had a positive PCR test between December 31, 2019, and August 4, 2020. The RT-PCR test results for 4079 individuals who had close contact with the re-positive cases were also obtained. RESULTS: In total, 2466 (12.16%) of the 20,280 patients had a re-positive SARS-CoV-2 PCR test after they were discharged from the hospital, and 4079 individuals had close contact with members of this patient group. All of these 4079 individuals had a negative SARS-CoV-2 PCR test. CONCLUSIONS: This retrospective study in Wuhan analyzed the basic characteristics of recovered COVID-19 patients with re-positive PCR test and found that these cases may not be infectious.

Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.

Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.

[Multiple-scale intermuscular coupling network analysis].

In order to more accurately and effectively understand the intermuscular coupling of different temporal and spatial levels from the perspective of complex networks, a new multi-scale intermuscular coupling network analysis method was proposed in this paper. The multivariate variational modal decomposition (MVMD) and Copula mutual information (Copula MI) were combined to construct an intermuscular coupling network model based on MVMD-Copula MI, and the characteristics of intermuscular coupling of multiple muscles of upper limbs in different time-frequency scales during reaching exercise in healthy subjects were analyzed by using the network parameters such as node strength and clustering coefficient. The experimental results showed that there are obvious differences in the characteristics of intermuscular coupling in the six time-frequency scales. Specifically, the triceps brachii (TB) had relatively high coupling strength with the middle deltoid (MD) and posterior deltoid (PD), and the intermuscular function was closely connected. However, the biceps brachii (BB) was independent of other muscles. The intermuscular coupling network had scale differences. MVMD-Copula MI can quantitatively describe the relationship of multi-scale intermuscular coupling strength, which has good application prospects.

Constraining Homo- and Heteroanion Dimers in Ultraclose Proximity within a Self-Assembled Hexacationic Cage.

A hexacationic cage 36+ was synthesized via hydrazone condensation in aqueous acid. Cage 36+ bears three biscationic arms, each of which contains four relatively acidic protons, including one NH and three CH protons. These hydrogen bond donors, as well as its intrinsic cationic nature, enable cage 36+ to encapsulate two anions concurrently within its cavity. The axial asymmetrical nature of the biscationic arms allow the cage to recognize two different anions in a selective manner, to encompass bound heteroanion dimers, such as Cl-·NO3- and Cl-·Br-. Single crystal X-ray diffraction analyses reveal that in the solid state the two anions are constrained in ultraclose proximity within the cage; e.g., the Cl-···Cl- and Cl-···Br- distances are 3.2 and 2.9 Å, respectively, which are shorter than the sum of their van der Waals radii. Evidence consistent with the sequential binding of two identical or disparate anions in CD3CN is also presented.

A single-component yet multifunctional tongue-mimicking sensor array for upconversion fluorescence biosensing.

In this work, we prepared a type of multiplexing upconversion nanoparticle (UCNP). There are three fluorescence emission peaks when our UCNPs are excited with 980 and 808 nm lasers. These fluorescence peaks of UCNPs can be quenched ("turn off") to varying degrees via fluorescence resonance energy transfer (FRET) when the UCNPs are coated with a polydopamine (PDA) layer, which is a universal quencher self-polymerized from dopamine (DA). Here, we create a novel single-component nanoprobe that can be used for the pattern recognition of antioxidants in a "turn on" manner by integrating with the prevention of PDA formation with an antioxidant. Our sensing strategy is based on the recovery of the fluorescence intensity of three emission peaks to different degrees due to different antioxidants with differential inhibition of PDA formation. Then, these three fluorescence emission peaks of UCNPs are innovatively selected as the sensor array, which enables us to discriminate multiple antioxidants and their mixtures. Simultaneously, the sensor array shows excellent performance in the chiral discrimination of cysteine enantiomers. This is a novel, innovative sensor array that requires only a single component to achieve the upconversion fluorescence pattern and recognize chiral molecules, and it elucidates a more innovative concept towards widespread applications.

Clinical Features of CVT in Women and Effect on Subsequent Pregnancy: A Follow-Up Study in a Chinese National Comprehensive Hospital.

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is not rare in women of childbearing age. Chinese couples have been encouraged to have two children by the new family-planning policy. Concerns have been raised about the effect of CVT on subsequent pregnancies, but few studies have focused on the Chinese population. We aimed to analyze the clinical features of Chinese female CVT patients of childbearing age and study the outcome of their subsequent pregnancies after CVT. METHODS: We retrospectively analyzed the clinical data of female patients at fertile age (15-45 years) diagnosed with CVT in our hospital between January 2009 and January 2019. Information on recurrence of venous thrombotic events as well as obstetrical outcomes of subsequent pregnancies was obtained and evaluated during follow-up. RESULTS: A total of 72 patients were enrolled, mean age at CVT onset was 29.4 ± 7.9 years. The main risk factors included autoimmune system disease (27.8%), pregnancy or puerperium (12.5%), and inherited thrombophilia (11.1%). Furthermore, 58 patients were followed up for a mean time of 63.1 ± 31.4 months and 17 new pregnancies occurred in 13 women. Among the 17 pregnancies, one CVT (5.9%) recurred in a patient with antiphospholipid syndrome. Overall, 10 (58.8%) pregnancies resulted in the birth of healthy children, including 8 full-term and 2 preterm births; 7 were terminated, including 3 (17.6%) spontaneous abortions. All patients with spontaneous abortions had antiphospholipid syndrome or Behcet's disease. CONCLUSIONS: Autoimmune system disease was the most common risk factor in Chinese female CVT patients. Recurrent pregnancy-associated CVT was infrequent in women with prior CVT, but attention should be paid during subsequent pregnancies.

Wi-Alarm: Low-Cost Passive Intrusion Detection Using WiFi.

In this paper, we present a WiFi-based intrusion detection system called Wi-Alarm. Motivated by our observations and analysis that raw channel state information (CSI) of WiFi is sensitive enough to monitor human motion, Wi-Alarm omits data preprocessing. The mean and variance of the amplitudes of raw CSI data are used for feature extraction. Then, a support vector machine (SVM) algorithm is applied to determine detection results. We prototype Wi-Alarm on commercial WiFi devices and evaluate it in a typical indoor scenario. Results show that Wi-Alarm reduces much computational expense without losing accuracy and robustness. Moreover, different influence factors are also discussed in this paper.

Joint Optimization of Interference Coordination Parameters and Base-Station Density for Energy-Efficient Heterogeneous Networks.

Heterogeneous networks (HetNets), consisting of macro-cells and overlaying pico-cells, have been recognized as a promising paradigm to support the exponential growth of data traffic demands and high network energy efficiency (EE). However, for two-tier heterogeneous architecture deployment of HetNets, the inter-tier interference will be challenging. Time domain further-enhanced inter-cell interference coordination (FeICIC) proposed in 3GPP Release-11 becomes necessary to mitigate the inter-tier interference by applying low power almost blank subframe (ABS) scheme. Therefore, for HetNets deployment in reality, the pico-cell range expansion (CRE) bias, the power of ABS and the density of pico base stations (PBSs) are three important factors for the network EE improvement. Aiming to improve the network EE, the above three factors are jointly considered in this paper. In particular, we first derive the closed-form expression of the network EE as a function of pico CRE bias, power reduction factor of low power ABS and PBS density based on stochastic geometry model. Then, the approximate relationship between pico CRE bias and power reduction factor is deduced, followed by a linear search algorithm to get the near-optimal pico CRE bias and power reduction factor together at a given PBS density. Next, a linear search algorithm is further proposed to optimize PBS density based on fixed pico CRE bias and power reduction factor. Due to the fact that the above pico CRE bias and power reduction factor optimization and PBS density optimization are optimized separately, a heuristic algorithm is further proposed to optimize pico CRE bias, power reduction factor and PBS density jointly to achieve global network EE maximization. Numerical simulation results show that our proposed heuristic algorithm can significantly enhance the network EE while incurring low computational complexity.

The roles of interleukin-1 and RhoA signaling pathway in rat epilepsy model treated with low-frequency electrical stimulation.

This study aims to explore the correlation between interleukin-1 (IL-1) and epilepsy in rats when treated with low-frequency electrical stimulation via the RhoA/ROCK signaling pathway. Twenty-four SD rats were elected for this study, among which six rats were assigned as the normal group. And 16 rat models with epilepsy were successfully established and assigned into the model group, the ES group and the ES + IL-8 group, with each group comprising of six rats. The seizure frequency and duration was recorded. Electroencephalogram (EEG) power was detected at α1, α2, ß, θ, and δ. The mRNA expressions of IL-1ß and IL-1R1 were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the protein expressions of RhoA, ROCK I and ROCK II were detected by western blotting. In comparison with the model group, the seizure frequency duration, the power of δ, θ, α1, α2, and ß, the mRNA and protein expressions of IL-1ß and IL-1R1, the expressions of RhoA and ROCK I proteins, and the ratio of RhoA protein between membrane and cytosol decreased in the ES group, while the expression of ROCK II increased (all P < 0.05). There was no significant difference in these indexes between the ES + IL-8 group and the model group (all P > 0.05). These findings signified that IL-1 might inhibit the efficacy of low-frequency ES for epilepsy via the RhoA/ROCK signaling pathway, which may provide a theoretical basis for clinical treatment of epilepsy.