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Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein.To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs).On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed.Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]).Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.

We propose and experimentally study a novel, to the best of our knowledge, quantum noise stream cipher (QNSC) secure transmission scheme based on the delta-sigma modulation (DSM) technique. The cooperation of the QNSC and DSM mechanisms makes it possible to transmit an ultrahigh-order encrypted signal in the non-return-to-zero (NRZ) on-off keying (OOK) format. The delivery of the NRZ OOK waveform over the fiber link allows us to send and receive signals using digital ports, instead of high-speed and high-resolution digital-to-analog converters (DACs) and analog-to-digital converters (ADCs) in conventional QNSC systems. Meanwhile, clock synchronization can be achieved by using a simple clock data recovery algorithm. The extra clock signal transmission link in conventional QNSC systems is no longer needed. The proposed scheme is also compatible with wavelength division multiplexing (WDM) systems. In this work, 4 × 12.9 Gbit/s plaintext is encrypted to a 65,536-level QNSC signal and then transmitted over a 10-km standard single-mode fiber. The transmitter and receiver are established by commercial 100G QSFP28 optical modules with clock data recovery. This proposed scheme can be easily deployed in commercial systems due to its minimalist implementation architecture and relatively low hardware cost.

Acidic nuclear phosphoprotein 32 family member e (Anp32e) has been reported to contribute to early mammalian development and cancer metastasis. However, the pathophysiological role of Anp32e in renal interstitial fibrosis (RIF) is poorly understood. Here, we demonstrated that Anp32e was highly expressed in the region of RIF in patients with IgA nephropathy, unilateral ureteral obstruction (UUO) mouse kidneys, and Boston University mouse proximal tubular (BUMPT) cells when treated with TGF-β1; this upregulation was positively correlated with the total fibrotic area of the kidneys. The overexpression of Anp32e enhanced the TGF-β1-induced production of fibrosis-related proteins (fibronectin (Fn) and collagen type I (Col-I)) in BUMPT cells whereas the knockdown of Anp32e suppressed the deposition of these fibrosis-related proteins in UUO mice and TGF-β1-stimulated BUMPT cells. In particular, Anp32e overexpression alone induced the deposition of Fn and Col-I in both mouse kidneys and BUMPT cells without TGF-β1 stimulation. Furthermore, we revealed that the overexpression of Anp32e induced the expression of TGF-β1 and p-Smad3 while TGF-β1 inhibitor SB431542 reversed the Anp32e-induced upregulation of Fn and Col-I in BUMPT cells without TGF-β1 stimulation. Collectively, our data demonstrate that Anp32e promotes the deposition of fibrosis-related proteins by regulating the TGF-β1/Smad3 pathway.

Prenatal ethanol exposure (PEE) could increase offspring’s susceptibility to adult liver lipid-metabolism diseases. This study aimed to confirm intrauterine programming mechanism of glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis for liver dysfunction in offspring rats induced by PEE. The results showed that levels of hepatic IGF1, lipid metabolism-related enzymes (e.g. FASN and HMGCR) and serum phenotype (TG, TCH, HDL-C, and LDL-C) were low in fetal rats of PEE but high in adult offspring except for HDL-C, meanwhile, hepatic H3K9ac and expression levels of IGF1 were low in fetal rats but high in adult offspring. Furthermore, levels of serum corticosterone and hepatic glucocorticoid-activation system (mainly including expression of 11β-HSD1, GR, and C/EBPα as well as 11β-HSD1/11β-HSD2 ratio) were high in fetal rats of PEE but low or unchanged in adult offspring. The adult F2 generation of PEE maintained the same GC-IGF1 axis programming alteration as the F1 generation despite gender differences. In vitro, cortisol was proved to activate hepatocyte glucocorticoid-activation system and decrease H3K9ac and expression levels of IGF1 by GR. Therefore, PEE has a long-term effect on the offspring’s liver functional development, which may be mainly related to the epigenetic programming alteration of the GC-IGF1 axis mediated by the glucocorticoid-activation system.

Norcantharidin (NCTD), the demethylated analog of cantharidin isolated from Mylabris, is known to inhibit renal fibrosis. However, the underlying mechanism is largely unknown. The present study investigates whether NCTD exerts this effect through regulation of the protein phosphatase 2A catalytic subunit (PP2Ac)-Smad3 pathway. HK-2 human renal proximal tubule cells exposed to transforming growth factor (TGF)-β1 were used as an in vitro model of renal fibrosis. The levels of total Smad3, C-terminal-phosphorylated Smad3 (p-Smad3), PP2Ac, and fibronectin (Fn) were evaluated by Western blotting. A PP2Ac overexpression plasmid and the PP2Ac inhibitor okadaic acid (OA) were used for functional analyses. The subcellular localization of Smad3 was visualized by immunofluorescence labeling. The results showed that PP2Ac overexpression increased Smad3 phosphorylation and nuclear translocation in HK-2 cells, while pharmacologic inhibition of PP2Ac with OA had the opposite effect. NCTD suppressed Fn and p-Smad3 expression and TGF-β1-induced nuclear entry of Smad3, but these effects were abrogated by inhibition of PP2Ac. Thus, the anti-renal interstitial fibrosis effect of NCTD is exerted through inhibition of PP2Ac-mediated C-terminal phosphorylation of Smad3. These findings highlight the therapeutic potential of NCTD for the treatment of renal interstitial fibrosis.

We propose and experimentally study a coherent optical chaotic secure transmission system through a multi-core fiber (MCF). The messages are encrypted by the chaotic carrier and transmitted through the outer cores of the MCF, whereas the chaotic carrier signal is concealed by transmitting through the center core. The MCF provides large transmission capacity expansion and security enhancement against eavesdroppers due to its physical structure. In addition, the designed optical chaos self-homodyne coherent detection strategy has high detection sensitivity and simple physical structure. Due to the prevalence of devices and digital signal processing (DSP) algorithms used in this system, it can be well compatible with a commercial coherent optical communication system. Error free 40 Gb/s/core encrypted 16 quadrature amplitude modulation (QAM) signal transmission over 10 km 7-core fiber is achieved, and 20 Gb/s quadrature phase shift keying (QPSK) signal transmission over a 100 km standard single-mode fiber (SSMF) is demonstrated to verify the long-distance transmission capability. The sensitivity to the secret key is also studied.

We propose and experimentally study a coherent optical secure transmission system based on one dual-polarization in-phase and quadrature modulator (IQM). One beam of the polarized light is used to generate broadband chaos by configuring a nonlinear opto-electronic oscillator while the other beam carries the encrypted signal. The encrypted signal is obtained through sequential encryption of the analog and digital chaos. The mutual mask of the hybrid chaotic signals can effectively enhance the security performance. Moreover, by varying the encryption depth of analog and digital vectors, the transmission performance can be flexibly adjusted. A commercial dual-polarization IQM could simultaneously generate a chaotic signal and a load message, which provides a high-integration solution. A fast independent component analysis (ICA) algorithm is adopted to compensate for the rotation of state of polarization (RSOP). 60 Gb/s encrypted quadrature phase shift keying (QPSK) signal transmission over 100 km single-mode fiber is realized, and the decrypted bit error rate (BER) performance is below the 7% forward error correction (FEC) threshold (BER = 3.8 × 10−3).

Background As a common phenotype in chronic kidney disease, renal interstitial fibrosis has been largely studied. Norcantharidin (NCTD), a derivative of naturally occurring cantharidin, has an anti-renal fibrotic effect. However, its underlying mechanisms of the protective role remain largely unknown. Long noncoding RNAs (lncRNAs) play vital parts in tissue homeostasis modulation under pathophysiological conditions. In this study, we discovered the underlying lncRNAs and genes, which may contribute to the anti-renal fibrotic effects of NCTD. Methods RNA-seq analysis was performed to evaluate profiling of lncRNAs and messenger RNAs (mRNAs) in kidney tissues of sham-control, and unilateral ureteral obstruction (UUO) mouse models with or without NCTD treatment. Systematic bioinformatic analysis of expression levels was used in lncRNAs and mRNAs of NCTD-treated UUO kidneys. Altered expression of lncRNAs and mRNAs levels was confirmed by quantitative real-time polymerase chain reaction analysis. Results 467 lncRNAs and 1502 mRNAs were differentially expressed between UUO- and sham-operated kidneys, and notably, these alterations in UUO-operated kidney were partially reversed following NCTD treatment. Interestingly, the up-regulation of lncRNA Gm16076, Gm26669, and down-regulation of Fam120aos were highly correlated with the up-regulation of mRNA levels of fibrosis-related gene ITGB1, STAT3 and reduction of Pink1 in UUO kidney, respectively. Conclusions The result suggested lncRNAs-regulated genes may contribute to the anti-renal fibrotic effect under NCTD treatment, and thus targeting lncRNAs-controlled genes and their related molecular signaling pathways may serve as a promising therapeutic target in renal fibrosis treatment.

Clinical and animal studies have indicated that hypercholesterolemia has intrauterine developmental origin. Our previous studies showed that prenatal caffeine exposure (PCE) increased the serum total cholesterol (TCH) levels in adult offspring rats. This study investigates the intrauterine programming mechanism of PCE male offspring rats susceptible to adult hypercholesterolemia. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg∙d) from gestational days (GD) 9 to 20. Male offspring were sacrificed under anesthesia at GD20 and postnatal week (PW) 12, and the serum and liver were collected. The effects of caffeine (0–100 μM, 24 h) on the expression of cholesterol synthesis related genes and their epigenetic mechanisms were confirmed in L02 cells. The results showed that PCE induced higher levels of serum TCH, LDL-C and higher ratios of TCH/HDL-C and LDL-C/HDL-C. Furthermore, the high levels of histone acetylation (via H3K14ac and H3K27ac) and the expression of genes (Srebf2, Hmgcr, Hmgcs1) were responsible for cholesterol synthesis. The results of PCE offspring in utero and the data in vitro exhibited similar changes, and accompanied by the reduced expression of adenosine A2A receptor (A2AR), cyclic adenosine monophosphate (cAMP), sirtuin1 and protein kinase A (PKA). These changes could be reversed by A2AR agonist (CGS-21680), cAMP agonist (forskolin) and sirtuin1 agonist (resveratrol). Therefore, our results confirmed that caffeine could enhance histone acetylation and expression levels of genes responsible for cholesterol synthesis via inhibiting the A2AR/cAMP/PKA pathway and down-regulating sirtuin1, which continued throughout adulthood and elevated hepatic cholesterol synthesis and hypercholesterolemia in the male offspring rats.

We report a secure key distribution (SKD) scheme based on broadband opto-electronic Boolean chaos and polarization modulation for higher secure key generation rate (KGR). An error-free SKD with KGR of 3.6 Gb/s is experimentally demonstrated.

Caffeine has developmental toxicity. Prenatal caffeine exposure (PCE) caused intrauterine growth retardation (IUGR) and multiple organ dysplasia. This study intended to explore the effect and mechanism of PCE on long bone development in female fetal rats. In vivo, the PCE group pregnant rats were given different concentrations of caffeine during the gestational Day 9-20. The mRNA expression of osteogenesis-related genes were significantly reduced in PCE group. In the PCE group (120 mg/kg·d), the length and primary center of fetal femur were shorter, and accompanied by H-type blood vessel abundance reducing. Meanwhile, connective tissue growth factor (CTGF) expression decreased in the growth plate of the PCE group (120 mg/kg·d). In contrast, the miR375 expression increased. In vitro, caffeine decreased CTGF and increased miR375 expression in fetal growth plate chondrocytes. After co-culture with caffeine-treated chondrocytes, the tube formation ability for the H-type endothelial cells was decreased. Furthermore, CTGF overexpression or miR375 inhibitor reversed caffeine-induced reduction of tube formation ability, and miR375 inhibitor reversed caffeine-induced CTGF expression inhibition. In summary, PCE decreased the expression of CTGF by miR375, ultimately resulting in H-type blood vessel-related long bone dysplasia.

Background: The purpose of this meta-analysis is to compare the efficacy and safety of aspirin and rivaroxaban in the prevention of venous thromboembolism (VTE) following either total knee arthroplasty or total hip arthroplasty. Methods: A comprehensive literature search of several electronic databases (PubMed, Embase, and Web of Science) was conducted to identify relevant studies. Outcomes of interest included VTE rate, deep vein thrombosis (DVT) rate, pulmonary embolism rate, major bleeding events, mortality rate, blood transfusion, and wound complication. Risk ratio (RR) with 95% confidence intervals (95%CIs) were calculated using a fixed-effects model or random-effects model. Results: A total of 8 studies with 97,677 patients met the inclusion criteria and were included in this meta-analysis. Compared with rivaroxaban, aspirin had a significantly higher incidence of DVT (RR = 1.48, 95%CI: 1.27, 1.72; P

We propose a greedy minimum mean squared error (MMSE)-based antenna selection algorithm for amplify-and-forward (AF) multiple-input multiple-output (MIMO) relay systems. Assuming equal-power allocation across the multi-stream data, we derive a closed form expression for the mean squared error (MSE) resulted from adding each additional antenna pair. Based on this result, we iteratively select the antenna-pairs at the relay nodes to minimize the MSE. Simulation results show that our algorithm greatly outperforms the existing schemes., Comment: SPL

In this letter, we study relay-aided networks with presence of single eavesdropper. We provide joint beamforming design of the source and relay that can minimize the overall power consumption while satisfying our predefined quality-of-service (QoS) requirements. Additionally, we investigate the case that the channel between relay and eavesdropper suffers from channel uncertainty. Finally, simulation results are provided to verify the effectiveness of our algorithm., Comment: CL

In this paper, we propose a sequential and incremental precoder design for downlink joint transmission (JT) network MIMO systems with imperfect backhaul links. The objective of our design is to minimize the maximum of the sub-stream mean square errors (MSE), which dominates the average bit error rate (BER) performance of the system. In the proposed scheme,we first optimize the precoder at the serving base station (BS), and then sequentially optimize the precoders of non-serving BSs in the JT set according to the descending order of their probabilities of participating in JT. The BS-wise sequential optimization process can improve the system performance when some BSs have to temporarily quit the JT operations because of poor instant backhaul conditions. Besides, the precoder of an additional BS is derived in an incremental way, i.e., the sequentially optimized precoders of previous BSs are fixed, thus the additional precoder plays an incremental part in the multi-BS JT operations. An iterative algorithm is designed to jointly optimize the sub-stream precoder and sub-stream power allocation for each additional BS in the proposed sequential and incremental optimization scheme. Simulations show that, under the practical backhaul link conditions, our scheme significantly outperforms the autonomous global precoding (AGP) scheme in terms of BER performance., Comment: TVT

We experimentally investigated a novel broadband optoelectronic chaos generation scheme. The proposed system is achieved by adopting the highly nonlinear operation of an electro-optical exclusive-NOR (XNOR) logic gate and two delayed feedback loops that refer to the Boolean chaos model. The XNOR gate is established by a commercial use inphase and quadrature-phase (IQ) modulator that works at a specific bias point. The resulting power spectrum of the broadband chaos signal extends from DC to 29.1 GHz (10 dB bandwidth), and the probability density distribution is Gaussian distribution like. Owing to the strong nonlinearity of XNOR operation, the conditions to enter the chaos region are more relaxed compared to traditional optoelectronic oscillator (OEO) chaos systems, and the time delay signature (TDS) of the feedback loop is also suppressed. Moreover, to further enhance the performance of the generated chaos signal, we injected the optoelectronic chaotic signal into a semiconductor laser. Experimental results indicate that after the cascade optical injection, the bandwidth of the output chaos signal is extended to 38.4 GHz and the TDS is completely concealed; meanwhile, a perfect Gaussian distribution can be obtained.

We propose and numerically investigate a chaotic optical coherent secure communication scheme, which supports long-haul secure transmission for signals in advanced modulation formats. A hybrid optical chaos system is designed with coordination of digital and analog signals. The hybrid entropy source provides a broadband analog optical chaos signal, which could serve as the carrier to load quadrature amplitude modulation (QAM) data. Simultaneously, a digital binary signal generated from the entropy source is transmitted to establish long-haul chaotic synchronization. Coherent detection is utilized at the receiver, and a digital signal processing (DSP) algorithm is adopted to reduce transmission distortion. A 5 Gbaud 16QAM signal is encrypted by a phase chaos carrier with the effective bandwidth of 5.8 GHz. A bit error rate (BER) below forward error correction (FEC) can be achieved after transmitting over 1600 km based on digital-signal-induced chaos synchronization technology. Optimal launch power is investigated to minimize nonlinear effects of transmission links. System security is guaranteed by the high dynamical complexity of the chaotic source and the sensitive time delay as the secret key.

Aims This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo. Main methods In vitro, chondrocytes were treated with interleukin-1β (IL-1β, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo, the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain. Key findings In vitro, in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1β. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo, the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats. Significance In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage.

The performance of throughput, delay, and their tradeoff in mobile ad hoc networks (MANETs) has been investigated on different assumptions. Nevertheless, few papers consider the supportive infrastructure in MANETs. With the help of supportive infrastructure, i.e., cellular networks, the performance of throughput and delay in MANETs can be improved. The impact of supportive infrastructure on the throughput–delay tradeoff in MANETs is an open research point. In this paper, we are interested in the optimal throughput–delay tradeoff in MANETs with supportive infrastructure. We investigate the supportive infrastructure that only provides transmission pipes between distant nodes. We study the optimal throughput–delay tradeoff in MANETs on different assumptions such as different densities of nodes and base stations (BSs), discrete/continuous mobility models with various velocities, and the fast/slow mobility assumption. We obtain the asymptotically optimal throughput–delay tradeoff and propose transmission policies based on random linear coding (RLC) to achieve the optimal throughput–delay tradeoff asymptotically. From the obtained optimal throughput–delay tradeoff, we find that supportive infrastructure reduces the delay bound from velocity, which is a lower bound of delay caused by nodes' velocity. In particular, if supportive infrastructure can cover the entire network, then the delay bound from velocity vanishes when per-node throughput does not exceed a threshold. Moreover, we find that there also exists a delay bound from the transmission range of the instant transmission. In addition, we observe that, for the optimal throughput–delay tradeoff in the large throughput region, the case in the continuous mobility model outperforms the case in the discrete mobility model, and the case on the slow mobility assumption outperforms the case on the fast mobility assumption.

In this letter, we propose a novel component carrier on/off scheduling scheme using the learning-based prediction for LTE in the unlicensed spectrum. Particularly, we use Lyapunov optimization to improve the performance of packet throughput and energy consumption, and use Vapnik-Chervonenkis theory to analyze the gap between the predicted optimal value and the practical one. The simulation results show that the proposed scheme can deliver good trade-off between packet throughput and energy consumption by turning off some carrier components, especially when the traffic load is not high.

Aims This study investigated the role and mechanism of action of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the pathogenesis of renal interstitial fibrosis (RIF), and its involvement in the anti-RIF effect of norcantharidin (NCTD). Main methods Mice with unilateral ureteral obstruction and BUMPT mouse proximal tubular cells exposed to transforming growth factor (TGF)-β1 were used as in vivo and in vitro models of RIF, respectively. NCTD was administered to mice by intraperitoneal injection (0.075 mg kg−1·day−1). Hematoxylin–eosin and Masson's trichrome staining were performed to assess pathologic changes in the kidney. Immunohistochemistry, western blotting, and real-time PCR were performed to evaluate the expression of TWEAK and the fibrotic factors fibronectin (FN) and collagen type I (Col-I). The role of TWEAK in RIF and in the anti-RIF effect of NCTD was evaluated by TWEAK overexpression and neutralization with a specific antibody, and specific inhibitor of Mothers against decapentaplegic homolog (Smad)3 (SIS3) was used to examine the involvement of TGF-β1/Smad3 signaling. Key findings TWEAK was mainly expressed in renal tubules in mice; the level was markedly elevated in both in vivo and in vitro RIF models. TWEAK overexpression in BUMPT cells increased the levels of phosphorylated Smad3, FN, and Col-I, which were reduced by treatment with SIS3. NCTD suppressed FN and Col-I expression by blocking TWEAK-mediated Smad3 phosphorylation. Significance Upregulation of TWEAK contributes to RIF by promoting Smad3 phosphorylation, while NCTD inhibits this process.

Model lightweight aims to solve the problems of various large models for slow training and high resource requirement. Knowledge distillation can be a good solution to these problems. We built a lightweight model that meet the competition requirements and have prominent NLP capabilities. RoBERTa-tiny-clue was used as our backbone model. We tested the effect of soft labels and hard labels on knowledge distillation, made knowledge distillation, fine-tuned this model to get a lighter model with better performance, and then applied it downstream NLP tasks. We also adopted a series of data augmentation methods to improve the performance of the model on downstream tasks, customized different optimization solutions for four tasks. Based on open-source pre-trained model RoBERTa-tiny-clue and public available datasets, we achieved 15 times smaller and 10 times faster than BERT-base, and 95% of BERT-base performance on downstram NLP tasks. Using suitable data augmentation methods for the trained lightweight model, the performance of the model on various downstream tasks reaches or exceeds BERT-base.

Prenatal caffeine exposure (PCE) induces developmental toxicity of multi-organ and susceptibility to multi-disease in offspring. However, the effects of PCE on osteoarthritis susceptibility in adult offspring and its intrauterine programming mechanism remain to be further investigated. Here, we found that PCE induced susceptibility to osteoarthritis in male adult offspring rats, which was related to the inhibited function of cartilage matrix synthesis from fetuses to adults. Meanwhile, PCE consistently downregulated the H3K9ac and expression levels of transforming growth factor β receptor 1 (TGFβR1), and then blocked TGFβ signaling pathway, which contributed to the suppressed cartilage matrix synthesis. Moreover, the high level of corticosterone caused by PCE reduced the H3K9ac level on TGFβR1 promoter region through acting on glucocorticoids receptor (GR) and recruiting histone deacetylase 2 (HDAC2) into the nucleus of fetal chondrocytes. Taken together, PCE induced osteoarthritis susceptibility in male adult offspring rats, which was attributed to the low-functional programming of TGFβR1 induced by corticosterone via GR/HDAC2 signaling.

Prenatal nicotine exposure (PNE) could induce an increased susceptibility to multiple chronic diseases in adult offspring, that mainly caused by intrauterine maternal glucocorticoid (GC) over-exposure. We investigated the changes and inheritability of hepatic glucose and lipid metabolism caused by PNE, to decipher the possible intrauterine programming mechanism. Pregnant Wistar rats were administered subcutaneously with 2 mg/kg·d nicotine from gestational day (GD) 9∼20, and second-generation (F2) were set according to the mating between control females and PNE males. The results showed that serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in F1 fetal rats of PNE but higher in the F1 adult rats. Meanwhile, the activated states of hepatic glucocorticoid-activation system, including type 1 and type 2 11β-hydroxysteroid dehydrogenases (Hsd11b1/2), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and CCAAT enhancer binding protein α (Cebpa), were positively correlated with serum corticosterone levels but negatively correlated with the histone acetylation (H3K27ac) and expression levels of insulin-like growth factor 1 (Igf1) before and after birth. Furthermore, serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in both F2 fetal and adult rats of PNE, which were consistent with the hepatic changes of GC-IGF1 axis and the glucocorticoid-activation system. In conclusion, PNE could lead to inheritable changes of hepatic glucose and lipid metabolism, which are related to the intrauterine programming of GC-IGF1 axis induced by the glucocorticoid-activation system.

This study aimed to evaluate female adult offspring induced by prenatal caffeine exposure (PCE) are susceptible to non-alcoholic fatty liver disease (NAFLD) and to explore the underlying programming mechanisms. Pregnant rats were intragastrically administered caffeine (30, 60, and 120 mg/kg.d) on gestational day (GD) 9-20. The female adult offspring were randomly divided into three groups: offspring without or with chronic stress during postnatal week (PW) 10–12 and PW28 offspring. Results showed that PW28 PCE female offspring had a higher hepatic triglyceride content and Kleiner scores, accompanied by elevated serum corticosterone levels. Moreover, the expression levels of hepatic glucocorticoid receptor (GR), CCAAT enhancer binding protein α (C/EBPα), fatty acid synthetase (FASN) and the transcription factor-sterol regulatory element binding protein 1c (SREBP1c) were increased, but SIRT1 expression was decreased. The fetal rats and PW12 offspring with chronic stress exhibited similar changes as PW28 offspring, accompanied by increased levels of H3K14ac and H3K27ac in the SREBP1c and FASN gene promoters. These effects were also observed by treating L02 cells with cortisol and were partially reversed by GR or C/EBPα siRNA or treatment with the SIRT1 agonist resveratrol. Taken together, PCE-induced high glucocorticoids levels enhanced histone modifications and expression of SREBP1c and FASN via activation of the GR-C/EBPα-SIRT1 pathway in utero. This enhanced female fetal hepatic triglyceride synthesis and continued throughout postnatal and adult life, increasing the susceptibility to adult NAFLD.

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30-120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8-20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta.

In this paper, we study the impact of human mobility on throughput and delay for people-centric applications in mobile ad hoc networks (MANETs). We consider a general human mobility model for MANETs, which can capture important features of human mobility, such as time correlation, node correlation, location heterogeneity, and node heterogeneity. Multiple unicasts with general arrival processes are delivered, and nodes are equipped with infinite buffers. Under our system model, we first characterize the network stability region in terms of the probability of each node set visiting each location and the amount of transmission resources at each location. We show that the node correlation and heterogeneity of locations' popularity usually decrease the size of the network stability region, whereas the diversity of locations visited by a node usually increases the size of the network stability region. Then, by solving a stability-related optimization problem, we develop a throughput-optimal policy based on the obtained optimal solution. We obtain the upper and lower bounds of the delay performance under the proposed policy. Finally, using simulations based on a theoretical model and some real traces, we verify the analytical results and compare the performance of the proposed policy with some existing policies.

In this paper, we analyze the impact of network coding (NC) configuration on the performance of ad hoc networks with the consideration of two significant factors, namely, the throughput loss and the decoding loss, which are jointly treated as the overhead of NC. In particular, physical-layer NC and random linear NC are adopted in static and mobile ad hoc networks (MANETs), respectively. Furthermore, we characterize the goodput and delay/goodput tradeoff in static networks, which are also analyzed in MANETs for different mobility models (i.e., the random independent and identically distributed (i.i.d.) mobility model and the random walk model) and transmission schemes (i.e., the two-hop relay scheme and the flooding scheme). Moreover, the optimal configuration of NC, which consists of the data size, generation size, and NC Galois field, is derived to optimize the delay/goodput tradeoff and goodput. The theoretical results demonstrate that NC does not bring about order gain on delay/goodput tradeoff for each network model and scheme, except for the flooding scheme in a random i.i.d. mobility model. However, the goodput improvement is exhibited for all the proposed schemes in mobile networks. To our best knowledge, this is the first work to investigate the scaling laws of NC performance and configuration with the consideration of coding overhead in ad hoc networks.

Epidemiological surveys suggest that adult hypercholesterolemia has an intrauterine origin and exhibits gender differences. Our previous study demonstrated that adult rats with intrauterine growth retardation (IUGR) offspring rats induced by prenatal caffeine exposure (PCE) had a higher serum total cholesterol (TCH) level. In this study, we aimed to analyze the influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy. Pregnant rats were administered caffeine (120 mg/kg d) from gestational day 11 until delivery. Offspring rats fed a normal diet or a high-fat diet (HFD) were euthanized at postnatal week 24, and blood and liver samples were collected. The results showed that PCE could increase the serum levels of TCH and low-density lipoprotein-cholesterol (LDL-C), and the hepatic expression of HMG CoA reductase (HMGCR) and apolipoprotein B (ApoB), but decreased the high-density lipoprotein-cholesterol (HDL-C) level and the hepatic expression of scavenger receptor B1 (SR-B1) and LDL receptor (LDLR). Furthermore, PCE, HFD and gender interact with each other to influence the serum cholesterol phenotype and expression of hepatic cholesterol metabolic genes. These results suggest that the hypercholesterolemia in adult offspring rats induced by PCE mainly resulted from enhanced synthesis and the weakened reverse transport of cholesterol in the liver, furthermore HFD could aggravate this effect, which is caused by hepatic cholesterol metabolic disorders. Moreover, cholesterol metabolism in female rats was more sensitive to neuroendocrine changes and HFD than that in males. This study confirmed the influencing factors (such as a HFD and female gender) of hypercholesterolemia in IUGR offspring providing theoretical and experimental bases for the effective prevention of fetal-originated hypercholesterolemia.

Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect.

Prenatal adverse environmental factors, including some xenobiotics, can induce intrauterine growth retardation (IUGR) and increase the susceptibility to adult metabolic diseases in the offspring. Food and beverages containing caffeine are increasingly consumed by pregnant women. According to epidemiological studies, prenatal caffeine ingestion can cause embryo or foetal developmental toxicities and is considered the primary cause of IUGR. Increasing evidence indicates that overexposure of the foetus to maternal glucocorticoids, resulting from prenatal caffeine ingestion, can exert powerful effects on the epigenome, influencing the expression of important developmental genes. Such influences alter the intrauterine programming of the hypothalamic–pituitary–adrenal (HPA) axis, which may increase the susceptibility to metabolic diseases (such as hypertension, diabetes, and non-alcoholic fatty liver disease) in adult offspring. The mechanism of intrauterine neuroendocrine metabolic programming responsible for the increased susceptibility to adult diseases in IUGR offspring caused by prenatal caffeine exposure is summarised in this review.

In this letter, we study robust beamforming design in the scenario that user equipments (UEs) relay the messages from a base station (BS) to a destination UE out of the cellular networks, which is considered as a high-priority device-to-device (D2D) scenario in the 3rd Generation Partnership Project (3GPP) Long-Term-Evolution (LTE) standardization. We assume that another D2D UE, which receives data from another D2D transmission group, coexists in the network, and it is interfered by D2D relay UEs. Moreover, the channel links between D2D relay UEs and the interfered UE are supposed to suffer from Gaussian errors due to low accuracy of channel estimation. Our optimization objective is to minimize the total transmission power at the BS and D2D relay UEs, while satisfying the signal-to-interference-plus-noise ratio (SINR) requirement of the destination D2D receiver and keeping the probability of low SINR event of the interfered D2D receiver smaller than a predefined threshold. Finally, we present the joint BS and D2D relay UE beamforming design, the effectiveness of which is verified by computer simulations.

In this paper, we use the Lyapunov optimization technique to develop scheduling policies for multiradio multichannel cognitive networks to optimize jointly the throughput and the average delay of a secondary network, with limited interference to primary users (PUs)' transmission. In particular, we consider three scenarios, including a static single-hop secondary network, a static multihop secondary network, and a mobile secondary network. For these cases, with the consideration of general mobility and interference models, we design efficient scheduling and channel allocation algorithms based on the concept of Lyapunov drift and give the corresponding performance bound. Furthermore, our theoretical analysis demonstrates that the proposed algorithms can achieve a flexible tradeoff between network throughput and average backlogs by using the Lyapunov optimization technique. Finally, the efficiency of the proposed algorithms is verified by the numerical simulations.

In this letter, we propose a novel dynamic cell on/off scheduling algorithm in small cell networks based on the Stackelberg game. The objective of the proposed algorithm is to optimize the packet throughput performance with a tradeoff of energy consumption. In our system-level simulations, the proposed algorithm exhibits considerable performance gains, in terms of packet throughput per unit of energy consumption, compared with two existing algorithms respectively based on random on/off and packet arrival-triggered cell activation.

In this paper, we investigate the robust beamforming for multi-user multiple-input single-output systems under quan- tized channel direction information (CDI) with per-antenna power constraints. The robustness of the considered beamforming design is achieved in the sense that the stochastic interference leakage is below a certain level by a given probability. Our design objective is to maximize the expectation of the weighted sum-rate per- formance. From the discussion of the non-robust optimal beam- forming based on the polyblock algorithm, we propose a robust beamforming scheme for the quantized CDI case with per-antenna power constraints. In the proposed beamforming scheme, we use Jensen's inequality to generate a tractable feasibility problem for the polyblock algorithm and apply the semi-definite programming relaxation, as well as the randomization technique to find its ap- proximate rank-one matrix solution and user equipments' beam- forming vectors. Simulation results show that substantial gains can be achieved by the proposed scheme compared with the existing schemes in terms of the average weighted sum-rate performance. Although very high complexity is required for the implementation of the proposed scheme, it stands as a good benchmark for robust beamforming designs.

In this paper, we analyze the physical layer abstraction for bit interleaved coded orthogonal frequency division multiplexing (BIC-OFDM) system from a parallel bit channel perspective. By combining the exponential effective SNR (signal-to-noise ratio) mapping (EESM) with the maximum a posteriori (MAP) algorithm, a bit LLR (log-likelihood ratio) wise EESM (BL-EESM) method is proposed. This method can abstract the link performance with high accuracy, especially for the case when channel estimation is imperfect. Afterward, the BL-EESM method is simplified by utilizing the non-linear quantization idea, which can reduce the times of exponential operation by two orders of magnitude at wide system bandwidth, yet shows little loss in accuracy. Our proposal can be applied to both system level simulations to save the time consumption and to practical terminals to facilitate the adaptive modulation and coding (AMC) procedure, bringing about throughput improvement at low hardware cost.

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2.

This paper studies the precoder design of bidirectional networks in which each node is equipped with multiple antennas. In contrast to the conventional model of bidirectional relay networks, this paper considers a more general scenario, i.e., a multi-user multi-relay network. First, by assuming that perfect channel state information (CSI) is available, we investigate the precoding design for the relays and users to minimize the sum mean squared error (MSE) and the maximum of single user's MSE, respectively. Then, we consider a more practical scenario where CSI estimation error is taken into account. By means of alternating optimization approach, we decompose the main problem into several decoupled subproblems with tractable solutions. It is shown that, in both the perfect and imperfect CSI cases, the proposed precoding algorithms outperform the existing solutions in terms of MSE and bit-error-rate (BER) performance.

Green communication receives a growing number of concerns due to the consideration for energy and environment issues. On the other hand, the evolution of mobile and wireless communication also results in heterogeneous Radio Access Technologies (RATs), such as Wi-Fi, UMTS, LTE, CDMA2000 and so on. As a result, energy saving by inter-RAT cooperation has raised significant discussions in both industrial and academical worlds. In this paper, we concentrate on inter-RAT energy saving for multicast services. Moreover, we use Integer Linear Programming to model the problem and propose a distributed algorithm which can efficiently save the energy consumption.

Existing minimum-mean-squared-error (MMSE) transceiver designs in amplified-and-forward (AF) multiple-input multiple-output (MIMO) two-way relay systems all assume a linear precoder at the sources. Nonlinear source precoders in such a system have not been considered yet. In this paper, we study the joint design of source Tomlinson-Harashima precoders (THPs), relay linear precoder and MMSE receivers in two-way relay systems. This joint design problem is a highly nonconvex optimization problem. By dividing the original problem into three sub-problems, we propose an iterative algorithm to optimize precoders and receivers. The convergence of the algorithm is ensured since the updated solution is optimal to each sub-problem. Numerical simulation results show that the proposed iterative algorithm outperforms other algorithms in the high signal-to-noise ratio (SNR) region.

In this paper, we consider a non-regenerative MIMO two-way relay system with imperfect channel state information (CSI). We employ a stochastic approach to model the channel uncertainties and address the robust joint source and relay optimization problem based on the minimum mean squared error (MMSE) criterion. With imperfect CSI, the self-interference (SI) cannot be completely canceled at destination nodes. Hence, both channel uncertainties and residual self-interference should be considered. We develop an optimization framework that unifies both frequency-division duplex (FDD) and time-division duplex (TDD) systems despite their different channel statistical properties. Two robust algorithms are proposed to minimize the sum mean squared error (MSE) averaged over channel uncertainties. The first algorithm adopts alternating optimization to update the source precoders, relay precoder and destination receivers iteratively with guaranteed convergence. In the second algorithm, only the relay precoder with certain structure is considered. Then the relay precoder design is reduced to the simple power allocation problem. Simulation results show that the proposed algorithms provide robustness against channel uncertainties, especially when the signal-to-noise ratio is high.

In this letter, we propose an antenna selection single frequency network precoding (AS-SFNP) scheme for downlink cooperative multiple-input multiple-output (MIMO) systems, which efficiently improves system capacity with low feedback overhead and low complexity.

Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20 and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE.

This letter proposes a robust joint linear precoding scheme based on the minimum mean squared error (MMSE) criterion for amplify-and-forward (AF) multiple-input multiple-output (MIMO) relay broadcast systems with limited feedback, where only the quantized channel direction information (CDI) of the forward channel is available for the base station (BS) and the relay station (RS). The proposed scheme employs an iterative algorithm which alternately optimizes the BS and RS precoders to jointly minimize the expected MSE conditioned on the quantized CDI.

This paper investigates the Resource allocation problem in OFDMA-based decode-and-forward cooperative communication systems. The objective is to maximize the sum throughput under the constraints of joint total transmission power and subchannels occupation, while maintaining the maximum fairness among multiple relay nodes. Since the optimal solution to this combinatorial problem is extremely computationally complex to obtain, we propose a low-complexity suboptimal algorithm that allocates subchannel and power separately. In the proposed algorithm, subchannel allocation over the relay nodes is first performed under the assumption of equal power distribution. Then, an optimal power allocation algorithm named multi-level water-filling is used to maximize the sum rate. The simulation results show that the performance of the proposed algorithm can approach asymptotically to that of the optimal algorithm while enhancing the fairness among all relay nodes and reducing computational complexity from exponential to linear with the number of subchannels. It is also shown that the proposed equal power distribution algorithm with subchannel permutation (SP) outperforms the one without SP.