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IEEE Keyword search problem has been widely studied to retrieve relevant substructures from graphs. However, existing approaches aim at finding compact trees/subgraphs containing the keywords, and ignore density to evaluate how strongly and stablely the keyword nodes are connected. In this paper, we study the problem of finding cohesive subgraph containing query keywords with high density and compactness, and formulate it as minimal dense truss search problem based on k-truss model. However, unlike ${k}$-truss based community search that can be efficiently done by local search from a given set of nodes, this problem is nontrivial as the keyword nodes to be included in the retrieved substructure is previously unknown. To tackle this problem, we first design a novel hybrid KT-Index that keeps the keyword and truss information compactly to support efficient search of dense truss with the maximum trussness ${G_{den}}$. Then, we develop a novel refinement approach to extract minimal dense truss from ${G_{den}}$, by checking each node at most once based on the anti-monotonicity property of k-truss, together with several optimization strategies including batch based deletion, early-stop based deletion, and local exploration. Extensive experimental studies on real-world networks validated the effectiveness and efficiency of our approaches.

Graph simulation is one of the most fundamental problems in graph processing and analytics. It can help users to generate new graphs on different scales to mimic observed real-life graphs in many applications such as social networks, biology networks, and information technology. In this paper, we focus on one of the most important types of graph generators: general graph generators, which aim to reproduce the properties of the observed graphs regardless of the domains. Though a variety of graph generators have been proposed in the literature, there are still several important research gaps in this area. In this paper, we first give an overview of the existing general graph generators, including recently emerged deep learning-based approaches. We classify them into four categories: simple model-based generators, complex model-based generators, autoencoder-based generators, and GAN-based generators. Then we conduct a comprehensive experimental evaluation of 20 representative graph generators based on 17 evaluation metrics and 12 real-life graphs. We provide a general roadmap of recommendations for how to select general graph generators under different settings. Furthermore, we propose a new method that can achieve a good trade-off between simulation quality and efficiency. To help researchers and practitioners apply general graph generators in their applications or make a comprehensive evaluation of their proposed general graph generators, we also implement an end-to-end platform that is publicly available.

We propose and numerically investigate infrared multi-narrowband tunable plasmonic induced transparency and its application as plasmonic sensor. Quasi-guided modes can be excited in Al2O3/SiO2 slab waveguide by the plasmonic periodic E shaped metallic nanostructures, which leads to multiple Fano-shaped transmission. The designed nanoparticle/slab waveguide/Si substrate structure exhibits multi-narrowband transparency and high reflectivity, which is easy to prepare and integrate. We further demonstrate electric tunability of multi Fano resonances by the introduction of larger-area graphene in the wavelength range 2000–3000 nm. Considering the multiple narrow bands and electric tunning performances of this structure, it is suitable to be utilized as a sensor. It shows that the figure of merit (FOM*) of the sensor can reach 66548 within the refractive index range 1.3-1.39. Moreover, the plasmonic sensor can also be used as a multiband optical switch with modulation depth up to 70%.

To describe the long-term health outcomes of patients with COVID-19 and investigate the potential risk factors. Clinical data during hospitalization and at a mean (SD) day of 249 (15) days after discharge from 40 survivors with confirmed COVID-19 (including 25 severe cases) were collected and analyzed retrospectively. At follow-up, severe cases had higher incidences of persistent symptoms, DLCO impairment, and higher abnormal CT score as compared with mild cases. CT score at follow-up was positively correlated with age, LDH level, cumulative days of oxygen treatment, total dosage of glucocorticoids used, and CT peak score during hospitalization. DLCO% at follow-up was negatively correlated with cumulative days of oxygen treatment during hospitalization. DLCO/VA% at follow-up was positively correlated with BMI, and TNF-α level. Among the three groups categorized as survivors with normal DLCO, abnormal DLCO but normal DLCO/VA, and abnormal DLCO and DLCO/VA, survivors with abnormal DLCO and DLCO/VA had the lowest serum IL-2R, IL-8, and TNF-α level, while the survivors with abnormal DLCO but normal DLCO/VA had the highest levels of inflammatory cytokines during hospitalization. Altogether, COVID-19 had a greater long-term impact on the lung physiology of severe cases. The long-term radiological abnormality maybe relate to old age and the severity of COVID-19. Either absent or excess of inflammation during COVID-19 course would lead to the impairment of pulmonary diffusion function.

Background Postoperative pain management is crucial for patients undergoing total knee arthroplasty (TKA). There have been many recent clinical trials on post-TKA peripheral nerve block; however, they have reported inconsistent findings. In this meta-analysis, we aimed to comprehensively analyze studies on post-TKA analgesia to provide evidence-based clinical suggestions. Methods We performed a computer-based query of PubMed, Embase, the Cochrane Library, and the Web of Science to retrieve related articles using neurothe following search terms: nerve block, nerve blockade, chemodenervation, chemical neurolysis, peridural block, epidural anesthesia, extradural anesthesia, total knee arthroplasty, total knee replacement, partial knee replacement, and others. After quality evaluation and data extraction, we analyzed the complications, visual analogue scale (VAS) score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices. Evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results We included 16 randomized controlled trials involving 981 patients (511 receiving peripheral nerve block and 470 receiving epidural block) in the final analysis. Compared with an epidural block, a peripheral nerve block significantly reduced complications. There were no significant between-group differences in the postoperative VAS score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices. Conclusions Our findings demonstrate that the peripheral nerve block is superior to the epidural block in reducing complications without compromising the analgesic effect and patient satisfaction. Therefore, a peripheral nerve block is a safe and effective postoperative analgesic method with encouraging clinical prospects.

Key points During exercise, bradykinin (BK), a muscle metabolite in ischaemic muscles, exaggerates autonomic responses to activation of muscle afferent nerves in peripheral artery disease (PAD). We examined whether BK inhibits activity of KV 4 channels in muscle afferent neurons of PAD rats induced by femoral artery occlusion. We demonstrated that: 1) femoral occlusion attenuates KV 4 currents in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles and decreases the threshold of action potential firing; 2) BK has a greater inhibitory effect on KV 4 currents in muscle DRG neurons of PAD rats; and 3) expression of KV 4.3 is downregulated in DRGs of PAD rats and inhibition of KV 4.3 significantly decreases activity of KV 4 currents in muscle DRG neurons. Femoral artery occlusion-induced limb ischaemia and/or ischaemia-induced metabolites (i.e. BK) inhibit activity of KV 4 channels in muscle afferent neurons and this is likely involved in the exaggerated exercise pressor reflex in PAD. Abstract Muscle afferent nerve-activated reflex sympathetic nervous and blood pressure responses are exaggerated during exercise in patients with peripheral artery diseases (PAD) and in PAD rats induced by femoral artery occlusion. However, the precise signalling pathways and molecular mediators responsible for these abnormal autonomic responses in PAD are poorly understood. A-type voltage-gated K+ (KV ) channels are quintessential regulators of cellular excitability in the various tissues. Among KV channels, KV 4 (i.e. KV 4.1 and KV 4.3) in primary sensory neurons mainly participate in physiological functions in regulation of mechanical and chemical sensation. However, little is known about the role of KV 4 in regulating neuronal activity in muscle afferent neurons of PAD. In addition, bradykinin (BK) is considered as a muscle metabolite contributing to the exaggerated exercise pressor reflex in PAD rats with femoral artery occlusion. Our data demonstrated that: 1) KV 4 currents are attenuated in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles of PAD rats, along with a decreasing threshold of action potential firing; 2) KV 4 currents are inhibited by application of BK onto muscle DRG neurons of PAD rats to a greater degree; and 3) expression of KV 4.3 is downregulated in the DRGs of PAD rats and KV 4.3 channel is a major contributor to the activity of KV 4 currents in muscle DRG neurons. In conclusion, data suggest that femoral artery occlusion-induced limb ischaemia and/or ischaemia-induced metabolites (i.e. BK) inhibit the activity of KV 4 channels in muscle afferent neurons likely leading to the exaggerated exercise pressor reflex observed in PAD.

Objective Numerous neuroimaging studies have demonstrated that functional brain aberrations are associated with cognitive impairments in temporal lobe epilepsy (TLE). Here, we aimed to investigate the neural substrates of attention deficits by combining assessment of regional intrinsic brain activities with large-scale functional connectivity in patients with right TLE (rTLE). Methods Thirty-five patients with rTLE and 33 matched healthy controls were recruited. All participants completed the Attention Network Test (ANT) and resting-sate functional MRI (rs-fMRI) scans. The z-standardized fractional amplitude of the low-frequency fluctuation (zfALFF) approach was applied to evaluate the brain's intrinsic activity. The cerebral regions with significant zfALFF values were selected as seeds for subsequent functional connectivity analyses. A correlation analysis was performed between functional activity and clinical variables. Results Compared with the healthy control group, the patients showed decreased zfALFF in the right inferior temporal gyrus and bilateral superior parietal gyrus, and the right inferior temporal gyrus exhibited increased functional connectivity with the bilateral cerebellum-6/vermis-6 and decreased functional connectivity with right superior frontal gyrus. The ANT indicated that the rTLE group exhibited attention deficits. Furthermore, a positive correlation was found between the zfALFF value of the left superior parietal gyrus and alerting performance, while a negative correlation between the zfALFF value of the right superior parietal gyrus and disease duration. Conclusion This study demonstrated aberrant intrinsic cerebral activity and functional connectivity in the whole brain network, which may act as responsible and compensatory factors in attention deficits, especially further profoundly illuminated the compensatory role of cerebellum in patients with rTLE.

Objective To introduce our experience of laparoscopic uterovaginal anastomosis and operative outcomes following this technique and update the clinical management of congenital cervicovaginal atresia. Study design Between March 2015 and January 2019, twenty-three patients with congenital cervicovaginal atresia underwent laparoscopic uterovaginal anastomosis and Luohu procedure. Their clinical characteristics, surgical outcomes and follow-up data were retrospectively reviewed. Results The mean ± SD age of the cases was 16.4 ± 4.0 (11–26) years. All patients had a history of primary amenorrhea and cyclical abdominal pain, and the average delay in diagnosis from first symptoms was 33.5 ± 38 (1–156) months. Most of the patients had 1−3 cm long vaginal pouch. The operative procedure lasted 125 ± 32 (80–190) min. The average vaginal length at 1 month was 7.9 ± 1.3 (range 6–9) cm. All patients showed resumption of menstruation. The patients were followed for a mean of 27 ± 13 (12–56) months. During the follow-up, cervical stenosis did not occur in any of the cases. Conclusion Laparoscopic uterovaginal anastomosis with Luohu procedure provided a minimally invasive, safe, and effective surgical option for the patients with congenital cervicovaginal atresia. The technique is uncomplicated, easy to learn and perform, and provides a functional and anatomic satisfactory result. No special surgical instruments are required with this technique.

The current study empirically tests the relationship between homicide rates and the population of indigenous Mayans at the municipal level in Guatemala. Using data from the most recent Guatemalan Census (2018) and independently aggregated national police data on homicides, we also propose models of possible pathways for the relationship between the ethnoracial composition of municipal population and homicide rates. Due to consistent non-normal distribution of demographic data in Guatemala, we used a maximum likelihood estimation of linear regression models and nonparametric bootstrapping method to test the theoretical relationships. The results showed a strong negative relationship between Mayan majority municipalities and homicide rates, mediated by living in municipality of birth. Findings suggest that attachment to place in Mayan majority municipalities in Guatemala is a strong protective factor for exposure to homicide, even in areas of high out-migration.

In peripheral artery disease patients, the blood supply directed to the lower limbs is reduced. This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs. The painful perception is induced and exaggerate during walking, and is relieved by rest. This symptom is termed by intermittent claudication. The limb ischemia also amplifies autonomic responses during exercise. In the process of pain and autonomic responses originating exercising muscle, a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses. This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle. For the sensory nerve receptors, we emphasize the role played by transient receptor potential vanilloid type 1, purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

Salmonella enterica serovar Pullorum (S. Pullorum) is an important pathogen specific to avian species, which poses a serious threat to the poultry industry. The transmission of S. Pullorum occurs b...

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a widely prevalent problem with many complications, such as hypertension and cerebral vascular diseases. Atherosclerosis, whose most severe outcome is ischemic stroke, is reported being affected by OSAHS. The objective of this article is to investigate the differences of carotid atherosclerosis patients with or without OSAHS by a cross-sectional research. Patients diagnosed with carotid atherosclerosis by ultrasonography were recruited. They were requested to fill the primary screening OSAHS questionnaire. Patients with high tendency of OSAHS underwent polysomnography (PSG) tests into OSAHS group, and patients without OSAHS were into non-OSAHS group. Blood tests and medical history were collected. Carotid atherosclerosis severity was analyzed by carotid artery intima-media thickness (IMT), carotid plaque, blood flow velocity, etc. Differences between the two groups and subgroups were analyzed. A total of 242 carotid atherosclerosis patients were enrolled including 118 non-OSAHS patients (38 males and 80 females) and 124 OSAHS patients (40 mild, 32 moderate, and 52 severe). Significant differences were found in PSV-ICA and EDV-ICA on both sides (p

In patients with peripheral artery disease (PAD), the blood supply directed to the lower limbs is reduced. This results in severe limb ischemia and thereby intermittent claudicating which is characterized by pain in lower limbs that occurs with walking and is relieved by rest. Of note, PAD can extremely affect the quality of living of patients and increase high risk of coronary and cerebral vascular accidents. However, effective treatments of PAD are still challenging in clinics. A number of reports have demonstrated the beneficial effects of supervised exercise on symptoms of PAD patients. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in sympathetic control of blood pressure response during exercise in PAD, and rationality of animal models used for study human PAD. Nonetheless, additional in-depth studies are necessary to better explore the underlying mechanisms of the exaggerated responses of sympathetic nerve and blood pressure in PAD at molecular and cellular levels.

Given a scientific collaboration network, how can we find a group of collaborators with high research indicator (e.g., h-index) and diverse research interests? Given a social network, how can we identify the communities that have high influence (e.g., PageRank) and also have similar interests to a specified user? In such settings, the network can be modeled as a multi-valued network where each node has d ( $$d \ge 1$$ ) numerical attributes (i.e., h-index, diversity, PageRank, similarity score, etc.). In the multi-valued network, we want to find communities that are not dominated by the other communities in terms of d numerical attributes. Most existing community search algorithms either completely ignore the numerical attributes or only consider one numerical attribute of the nodes. To capture d numerical attributes, we propose a novel community model, called skyline community, based on the concepts of k-core and skyline. A skyline community is a maximal connected k-core that cannot be dominated by the other connected k-cores in the d-dimensional attribute space. We develop an elegant space-partition algorithm to efficiently compute the skyline communities. Two striking advantages of our algorithm are that (1) its time complexity relies mainly on the size of the answer s (i.e., the number of skyline communities), and thus, it is very efficient if s is small; and (2) it can progressively output the skyline communities, which is very useful for applications that only require part of the skyline communities. In addition, we also develop three efficient graph reduction techniques to further speed up the proposed algorithms. Extensive experiments on both synthetic and real-world networks demonstrate the efficiency, scalability, and effectiveness of the proposed algorithm.

BackgroundImmune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients’ prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated.MethodsWe performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures.ResultsWe defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, we developed an SVM classifier to identify the patient’s immunological status, which was divided into Type A and Type B, in which Type A had poorer prognosis, higher T cell dysfunction despite higher T cell infiltration, and had better immunotherapeutic response. At the same time, MMP9 may be a potential predictor of the immune characteristics and immunotherapeutic response in HCC.ConclusionsOur work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response.

Femoral artery occlusion in rats has been used to study human peripheral artery disease (PAD). Using this animal model, a recent study suggests that increases in levels of tumor necrosis factor-α (TNF-α) and its receptor lead to exaggerated responses of sympathetic nervous activity and arterial blood pressure as metabolically sensitive muscle afferents are activated. Note that voltage-dependent Na+ subtype NaV1.8 channels (NaV1.8) are predominately present in chemically sensitive thin fiber sensory nerves. The purpose of this study was to examine the role played by TNF-α in regulating activity of NaV1.8 currents in muscle dorsal root ganglion (DRG) neurons of rats with PAD induced by femoral artery occlusion. DRG neurons from control and occluded limbs of rats were labeled by injecting the fluorescent tracer DiI into the hindlimb muscles 5 days before the experiments. A voltage patch-clamp mode was used to examine TTX-resistant (TTX-R) NaV currents. Results were as follows: 72 h of femoral artery occlusion increased peak amplitude of TTX-R [1,922 ± 139 pA in occlusion ( n = 11 DRG neurons) vs. 1,178 ± 39 pA in control ( n = 10), means ± SE; P < 0.001 between the 2 groups] and NaV1.8 currents [1,461 ± 116 pA in occlusion ( n = 11) and 766 ± 48 pA in control ( n = 10); P < 0.001 between groups] in muscle DRG neurons. TNF-α exposure amplified TTX-R and NaV1.8 currents in DRG neurons of occluded muscles in a dose-dependent manner. Notably, the amplification of TTX-R and NaV1.8 currents induced by TNF-α was attenuated in DRG neurons with preincubation with respective inhibitors of the intracellular signaling pathways p38-MAPK, JNK, and ERK. In conclusion, our data suggest that NaV1.8 is engaged in the role of TNF-α in amplifying muscle afferent inputs as the hindlimb muscles are ischemic; p38-MAPK, JNK, and ERK pathways are likely necessary to mediate the effects of TNF-α.

Key points During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD). We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats. With HT (increase in basal muscle temperature of ∼1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD. We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X3 and the increase in P2X currents in the muscle afferent neurons of PAD rats. Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement. Abstract The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD). We further determined if the temperature-sensitive P2X receptor is involved in the effects of HT. The pressor response to static muscle contraction and α,β-methylene ATP (αβ-me ATP, a P2X agonist) was examined. Western blot analysis was used to determine the protein levels of P2X3 in the dorsal root ganglion (DRG), and the whole cell patch clamp was used to examine the amplitude of P2X currents in the DRG neurons. The basal muscle temperature (Tm ) was lower in PAD rats than in control rats. Tm was increased by ∼1.5°C and this increase was maintained for 30 min. This HT protocol was performed tweice daily for three continuous days. A greater blood pressure (BP) response to contraction was observed in PAD rats. HT attenuated the amplification of the BP response in PAD rats. HT also attenuated the enhancement of the BP response induced by the arterial injection of αβ-me ATP in PAD rats. In addition, HT attenuated the upregulation of the P2X3 and increased P2X currents in the DRG neurons of PAD rats. In conclusion, previous heat exposure plays an inhibitory role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction of the activity of the P2X receptor pathway is probably a part of mechanisms leading to the beneficial effects of HT.

Background Plastic bronchitis (PB) frequently occurs as a serious postoperative complication of the Fontan procedure. The definitive causes of PB are unknown. Case presentation Herein, we report a pediatric case of PB secondary to adenoviral infection. A 4-year-old girl was admitted to the general pediatric ward for cough since 2 weeks and fever since 11 days. Consolidated lesions were noted in the right upper and both lower lung lobes. Extracorporeal membrane oxygenation was performed because the patient’s respiratory failure remained unalleviated despite the use of a ventilator. Bronchial dendritic casts were extracted using flexible bronchoscopy, and the patient’s breathing improved. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. The exfoliated cells of sputum and cells from bronchoalveolar lavage fluid were positive for adenoviral antigen. Human adenovirus 7 was detected by next-generation sequencing of the bronchoalveolar lavage fluid. The patient recovered and was discharged 39 days after admission without recurrence of cough or wheezing. Conclusions PB due to human adenovirus 7 infection should be considered in children with persistent respiratory failure. Flexible bronchoscopy should be performed early to confirm diagnosis and to remove any airway obstruction.

In social networks, the leave of critical users may significantly break network engagement, i.e., lead a large number of other users to drop out. A popular model to measure social network engagement is $k$ k -core, the maximal subgraph in which every vertex has at least $k$ k neighbors. To identify critical users, we propose the collapsed $k$ k -core problem: given a graph $G$ G , a positive integer $k$ k and a budget $b$ b , we aim to find $b$ b vertices in $G$ G such that the deletion of the $b$ b vertices leads to the smallest $k$ k -core. We prove the problem is NP-hard and inapproximate. An efficient algorithm is proposed, which significantly reduces the number of candidate vertices. We also study the user leave towards the model of $k$ k -truss which further considers tie strength by conducting additional computation w.r.t. $k$ k -core. We prove the corresponding collapsed $k$ k -truss problem is also NP-hard and inapproximate. An efficient algorithm is proposed to solve the problem. The advantages and disadvantages of the two proposed models are experimentally compared. Comprehensive experiments on nine real-life social networks demonstrate the effectiveness and efficiency of our proposed methods.

Objective: We aimed to explore functional connectivity (FC) and effective connectivity (EC) of the executive control networks (ECNs) and the default mode network (DMN) in patients with right-sided TLE (rTLE) by applying independent component analysis (ICA) and Granger causal analysis (GCA).Methods: Twenty-seven patients with rTLE and 20 healthy controls (HCs) matched for age, gender underwent resting-state functional magnetic resonance imaging and Attention Network Test (ANT).Results: The FC analysis showed compared to HCs, patients with rTLE demonstrated reduced FC strength in the right inferior parietal gyrus (IPG) and the right middle temporal gyrus (MTG). The left superior temporal gyrus (STG) displayed reduced FC values whereas the left thalamus revealed increased FC values in rTLE. ROI-wise GCA revealed that patients with rTLE displayed increased EC from the left thalamus to the left STG, and as well as enhanced EC from the right IPG to the right MTG compared to HCs. Voxel-wise GCA showed positive EC from the left thalamus to the left insula while the right middle occipital gyrus (MOG) exhibited increased EC to the right MTG in patients. The ANT results demonstrated executive dysfunction in patients compared to HCs. The increased FC in the left thalamus showed a negative association with ECF in patients.Conclusion: We speculated that recurrent seizures take effect on disruption among the brain networks, and self-modulation occurs simultaneously to compensate for cognitive decline. Our findings revealed new insights on the neuropathophysiological mechanisms of rTLE.

Objective: To observe the therapeutic effect of acupuncture-moxibustion at different intervals on persistent allergic rhinitis. Methods: A total of 90 patients conforming to the inclusion criteria were randomized into three groups named A, B and C by randomized block method. Patients in all three groups received the same treatment of acupuncture and herbal cake-partitioned moxibustion at the same acupoints, while the treatment frequency was different. Patients in group A received the treatment once a week, group B twice a week and group C three times a week, and all the treatment lasted for 4 weeks. The total nasal symptom score (TNSS), total ocular symptom score (TOSS) and Sino-nasal outcome test-20 (SNOT-20) were evaluated before and after treatment. The self-rating score of symptoms was evaluated during treatment and 2 weeks after treatment. Results: The total effective rate was 80.0% in group A, 93.3% in group B, and 100.0% in group C. The total effective rate in group A was statistically different from that in group B and group C (both P 0.05). After treatment, scores of TNSS, TOSS and SNOT-20 in all three groups dropped significantly, and statistically different from those before treatment (all P 0.05); after 4-week treatment, the score in group A was higher than that in group B and group C, and showed statistical significant (both P 0.05). Conclusion: All three protocols are effective for allergic rhinitis. With the increase of treatment frequency, the therapeutic efficacy with a treatment frequency of twice a week and three times a week is superior to that of once a week. Frequency of three times a week has a better long-term effect than once and twice a week, together with the least fluctuation of symptoms.

Background To robustly identify synergistic combinations of drugs, high-throughput screenings are desirable. It will be of great help to automatically identify the relations in the published papers with machine learning based tools. To support the chemical disease semantic relation extraction especially for chronic diseases, a chronic disease specific corpus for combination therapy discovery in Chinese (RCorp) is manually annotated. Methods In this study, we extracted abstracts from a Chinese medical literature server and followed the annotation framework of the BioCreative CDR corpus, with the guidelines modified to make the combination therapy related relations available. An annotation tool was incorporated to the standard annotation process. Results The resulting RCorp consists of 339 Chinese biomedical articles with 2367 annotated chemicals, 2113 diseases, 237 symptoms, 164 chemical-induce-disease relations, 163 chemical-induce-symptom relations, and 805 chemical-treat-disease relations. Each annotation includes both the mention text spans and normalized concept identifiers. The corpus gets an inter-annotator agreement score of 0.883 for chemical entities, 0.791 for disease entities which are measured by F score. And the F score for chemical-treat-disease relations gets 0.788 after unifying the entity mentions. Conclusions We extracted and manually annotated a chronic disease specific corpus for combination therapy discovery in Chinese. The result analysis of the corpus proves its quality for the combination therapy related knowledge discovery task. Our annotated corpus would be a useful resource for the modelling of entity recognition and relation extraction tools. In the future, an evaluation based on the corpus will be held.

AIM: To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane (rhNGF-AM) on corneal epithelial and nerve regeneration in rabbit model. METHODS: Freshly prepared human amniotic membrane (AM) were immersed into PBS buffer containing 100 or 500 μg/mL rhNGF for 15, 30, and 60min at 4℃. The in vitro release kinetics of rhNGF was measured with ELISA. For in vivo evaluation, the AM were immersed with 500 μg/mL rhNGF for 30min. Fifty-seven rabbits were selected to establish corneal epithelial defect model. In addition to the 19 rabbits in control group, 38 rabbits received AM transplantation with or without rhNGF after the removal of central epithelium. Corneal epithelial defect area, sub-epithelial nerve fiber density, corneal sensitivity, rhNGF contents in resident AM and corneas were measured after the surgery. RESULTS: rhNGF was sustained release from the AM within 14d in vitro, with the positive correlation with initial immersion concentration. The immersion of AM in 500 μg/mL rhNGF for 30min achieved the most stable release within 14d. After transplantation in rabbit cornea, a high concentration of rhNGF in resident rhNGF-AM and cornea was maintained within 8d. Corneal epithelial healing, nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rhNGF-AM transplantation when compared to simple AM transplantation (all P

Bipartite graphs arise naturally when modeling two different types of entities such as user-item, author-paper, and director-board. In recent years, driven by numerous real-world applications in these networks, mining cohesive structures in bipartite graphs becomes a popular research topic. In this paper, we propose the first cohesive-structure-based bipartite graph analytics system, CohBGA. The key innovative features of our system are as follows. Firstly, we involve several cohesive-structure-based models and statistics in our system to analyze bipartite graphs at different levels of granularity. Secondly, CohBGA has a user-friendly and interactive visual interface with various functional tools to meet users' diverse query requirements. Thirdly, we implement state-of-the-art algorithms in CohBGA to support efficient query processing. Furthermore, as a generic framework is designed in CohBGA, CohBGA is going to be an open-source bipartite graph analytics platform that allows researchers to evaluate the effectiveness of more cohesive-structure-based models and algorithms for bipartite graphs.

Background Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. Methods Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. Results NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1β mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors. Conclusions IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways. Trial registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).

Interleukin‐6 (IL‐6) via trans‐signaling pathway plays a role in modifying muscle sensory nerve‐exaggerated exercise pressor reflex in rats with ligated femoral arteries, but the underlying mechanisms are poorly understood. It is known that voltage‐gated potassium channel subfamily member Kv4 channels contribute to the excitabilities of sensory neurons and neuronal signaling transduction. Thus, in this study, we determined that 1) IL‐6 regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation and 2) Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway. We found that the protein levels of IL‐6 and its receptor IL‐6R expression were increased in the DRGs of PAD rats with 3‐day of femoral artery occlusion. Inhibition of muscle afferents’ IL‐6 trans‐signaling pathway (gp130) by intra‐arterial administration of SC144, a gp130 inhibitor, into the hindlimb muscles of PAD rats alleviated blood pressure response to static muscle contraction. On the other hand, we found that 3‐day femoral occlusion decreased amplitude of Kv4 currents in rat muscle DRG neurons. The homo IL‐6/IL‐6Rα fusion protein (H. IL‐6/6Rα), but not IL‐6 alone significantly inhibited Kv4 currents in muscle DRG neurons; and the effect of H. IL‐6/6Rα was largely reverted by SC144. In conclusion, our data suggest that via trans‐signaling pathway upregulated IL‐6 in muscle afferent nerves by ischemic hindlimb muscles inhibits the activity of Kv4 channels and thus likely leads to adjustments of the exercise pressor reflex in PAD., Interleukin‐6 (IL‐6) regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation. Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway.

Background Idiopathic pulmonary hemosiderosis (IPH) encompasses a rare and agnogenic group of diffuse alveolar capillary hemorrhagic diseases. Corticosteroid treatment is the globally preferred therapeutic strategy for IPH; however, it can cause immunodeficiency. Nocardia infection often occurs in immunocompromised patients and primarily involves the pleura and lungs. Herein, we describe a case of pediatric pulmonary Nocardia infection after the corticosteroid treatment of IPH. Case presentation A 7-year-old girl presented with chief complaints of pale complexion persisting for 1 year and a cough for 20 days. Abundant hemosiderin-laden macrophages were detected in the gastric juice, which supported the diagnosis of IPH. Uninterrupted doses of corticosteroids were administered during the last hospitalization. After nearly 2 months of corticosteroids therapy, the patient began to cough and produce a purulent sputum. Next-generation sequencing of the bronchoalveolar lavage fluid revealed Nocardia abscessus (N. abscessus) DNA. Linezolid was administered with good response, and the patient was discharged after 18 days of hospitalization. Her symptoms and pulmonary lesions had recovered, and the IPH appeared to be well-controlled with low dose of corticosteroids in follow-up. Conclusions Nocardia infection should be considered in the differential diagnoses for IPH patients receiving corticosteroid therapy, especially in patients with poor response to conventional empirical antibiotic therapy. Next-generation sequencing of bronchoalveolar lavage fluid may be used to quickly identify the Nocardia. Sulfonamides or linezolid are effective for pediatric pulmonary Nocardia infection.

Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women’s cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78–3.71, PCandida albicans (VVC) (OR 0.63, 95% CI 0.49–0.82, P P P P

Acute respiratory distress syndrome (ARDS) is a uniform progression of overwhelming inflammation in lung tissue with extensive infiltration of inflammatory cells. Neutrophil apoptosis is thought to be a significant process in the control of the resolution phase of inflammation. It has been proved that 5-Aza-2′-deoxycytidine (Aza) can inhibit cancer by activating death-associated protein kinase 1 (DAPK1) to promote apoptosis. However, the effect of DAPK1 on neutrophil apoptosis is unclear, and research on the role of Aza in inflammation is lacking. Here, we investigated whether Aza can regulate DAPK1 expression to influence the fate of neutrophils in ARDS. In vitro, we stimulated neutrophil-like HL-60 (dHL-60) cells with different concentrations of Aza for different durations and used RNA interference to up- or downregulate DAPK1 expression. We observed that culturing dHL-60 cells with Aza increased apoptosis by inhibiting NF-κB activation to modulate the expression of Bcl-2 family proteins, which was closely related to the levels of DAPK1. In vivo, ARDS was evoked by intratracheal instillation of lipopolysaccharide (LPS; 3 mg/kg). One hour after LPS administration, mice were treated with Aza (1 mg/kg, i.p.). To inhibit DAPK1 expression, mice were intraperitoneally injected with a DAPK1 inhibitor. Aza treatment accelerated inflammatory resolution in LPS-induced ARDS by suppressing pulmonary edema, alleviating lung injury and decreasing the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, Aza reduced the production of proinflammatory cytokines. However, administration of the DAPK1 inhibitor attenuated the protective effects of Aza. Similarly, the proapoptotic function of Aza was prevented when DAPK1 was inhibited either in vivo or in vitro. In summary, Aza promotes neutrophil apoptosis by activating DAPK1 to accelerate inflammatory resolution in LPS-induced ARDS. This study provides the first evidence that Aza prevents LPS-induced neutrophil survival by modulating DAPK1 expression. This study demonstrates a novel mechanism in neutrophil apoptosis. In vitro, 5-Aza-2′-deoxycytidine (Aza) promotes apoptosis by enhancing death-associated protein kinase 1 (DAPK1) expression and activity. In vivo, Aza treatment accelerates inflammatory resolution in lipopolysaccharide-induced acute respiratory distress syndrome by upregulating DAPK1 expression, resulting in apoptosis of neutrophils.

Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proved to be an important pathological feature of lung fibrosis. This study aimed to investigate whether RvD1 can attenuate mechanical ventilation-induced lung fibrosis. Human lung epithelial (BEAS-2B) cells were pretreated with RvD1 for 30 min and exposed to acid for 10 min before being subjected to mechanical stretch for 48 h. C57BL/6 mice were subjected to intratracheal acid aspiration followed by mechanical ventilation 24 h later (peak inspiratory pressure 22 cmH2O, positive end-expiratory pressure 2 cmH2O, and respiratory rate 120 breaths/min for 2 h). RvD1 was injected into mice for 5 consecutive days after mechanical ventilation. Treatment with RvD1 significantly inhibited mechanical stretch-induced mesenchymal markers (vimentin and α-smooth muscle actin) and stimulated epithelial markers (E-cadherin). Tert-butyloxycarbonyl 2 (BOC-2), a lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) antagonist, is known to inhibit ALX/FPR2 function. BOC-2 could reverse the beneficial effects of RvD1. The antifibrotic effect of RvD1 was associated with the suppression of Smad2/3 phosphorylation. This study demonstrated that mechanical stretch could induce EMT and pulmonary fibrosis and that treatment with RvD1 could attenuate mechanical ventilation-induced lung fibrosis, thus highlighting RvD1 as an effective therapeutic agent against pulmonary fibrosis associated with mechanical ventilation.

Background Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective. Aims The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA. Methods The regulatory miRNAs of WDHD1 in CCA expression chip were predicted, followed by determination of the miR-494 and WDHD1 expression in normal cholangiocyte tissues and CCA tissues. The related protein levels were determined. CCA cell migration, invasion, viability, and cell cycle distribution and the dosage-dependent effect of miR-494 on CCA cell growth were subsequently detected. Finally, tumorigenicity and lymph node metastasis (LNM) were measured. Results Initially, miR-194 affected the CCA development via negatively regulating WDHD1 and miR-494 which were downregulated while WDHD1 was upregulated in CCA. In addition, miR-494 overexpression elevated E-cadherin expression while decreased expressions of WDHD1, N-cadherin, Vimentin, Snail, Twist and MMP-9. Finally, overexpressed miR-494 was observed to suppress EMT, cell viability, migration, invasion, arrest cell cycle progression, tumor formation, and LNM while accelerating cell apoptosis in vivo. Conclusion This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.

In this paper, we demonstrate the light interaction mechanism of black phosphorus (BP) in two different structures: the photonic crystal waveguide (PCW) and photonic crystal mirror (PCM). The optical characteristics are simulated by the numerical method finite difference time domain. Specifically, the coupled mode theory is used to investigate the light propagation in PCW structure integrated with BP. By optimizing the geometric parameters, an enhanced light absorption in BP with the maximum of 36.8% at 1550 nm could be obtained. Additionally, with the assistance of BP film, the ultracompact PCM used for a 90° bend connection can achieve a high-reflective efficiency at ∼94% for transverse electric (TE) mode incidence. It is demonstrated that these interesting structures can offer a new way to develop ultracompact photonic integrations based on two-dimensional materials at near infrared field.

Advances of the sensor and GPS techniques have motivated the proliferation of trajectory data in a wide spectrum of applications. Trajectory similarity computation is one of the most fundamental problems in trajectory analytics. Considering that the high complexity of similarity computation is usually a bottleneck for large-scale trajectory data analysis, there are many research efforts for reducing the complexity such as the approximate algorithms. However, most of them are proposed for only one or two specific similarity measures, and thus cannot support different similarity measures well. In this paper, we propose a deep learning based model, namely T3S, which embeds each trajectory (i.e., a sequence of points) into a vector (point) in a d-dimensional space, and hence can significantly accelerate the similarity computation between the trajectories. By applying recurrent and attention neural networks, T3S can capture various unique characteristics of the trajectories such as the ordering of the points, spatial and structural information. Furthermore, our learning based T3S can easily handle any trajectory similarity measures by adjusting its parameters through the training. Extensive experiments on two real-life datasets demonstrate the effectiveness and efficiency of T3S. T3S outperforms state-of-the-art deep learning based methods under four popular trajectories similarity measures.

Background Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-β) signaling pathway is becoming a reality. However, the molecular characterization of TGF-β associated signatures in GIAD requires further exploration. Methods Multi-omics data were collected from TCGA and GEO database. A pivotal unsupervised clustering for TGF-β level was performed by distinguish status of TGF-β associated genes. We analyzed differential mRNAs, miRNAs, proteins gene mutations and copy number variations in both clusters for comparison. Enrichment of pathways and gene sets were identified in each type of GIAD. Then we performed differential mRNA related drug response by collecting data from GDSC. At last, a summarized deep neural network for TGF-β status and GIADs was constracted. Results The TGF-βhigh group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-βhigh group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-β. Further genomic analysis showed that TGF-βlow group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed tumor-sensitive or tumor-resistant drugs corresponding to TGF-β associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-β status in different GIAD datasets. Conclusions We provide molecular signatures associated with different levels of TGF-β to deepen the understanding of the role of TGF-β in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-β in GIAD.

With the increasing use of packaging, how to carry out green packaging has become an urgent problem. An important reason why packaging is difficult to reuse is that it is violently opened, making it difficult to recycle again. Many packaging structures on the market are cleverly designed and various packaging forms are available, but imperfect structures, materials, and information lead to violent use by users, so that the package is damaged, which is too hard to recycle. The development of augmented reality has brought a boom in information technology. We can pass the designed packaging which is combined with augmented reality technology to the user. In that way, the user can intuitively experience the use skills when using the package. We can utilize software such as Unity and Vuforia to model the packaging, import those usage methods such as opening, closing, and storage into the system, finally export the APP. Before using the package, the user can use application to identify the packaging structure on the package, obtaining the information of the 3D effect display about the packaging instructions before performing operations, which can not only protect the package from damage, but also increase the packaging utilization rate.

Background: Experienced surgeons most commonly utilize Magnetic Resonance Imaging (MRI) to diagnose rotator cuff tear (RCT) and predict the possibility of post-operative re-tear. Radiomics adjuvant therapy is widely used to improve the response prediction of clinical tasks. We validated a classifier to distinguish the status of rotator cuff tear and predict post-operative re-tear by utilizing MRI markers. Methods: We selected 101 patients with no abnormality in rotator cuff and 101 patients undergoing arthroscopic rotator cuff repair diagnosed as RCT by MRI. Radiomics features of RCT were identified from the pre-operative shoulder MRI. A radiomics model for diagnosis of RCT was constructed, based on the 3D volume of interest (VOI) of supraspinatus from 202 patients. Additionally, a model for prediction prognosis was made, based on VOI of humerus, supraspinatus, infraspinatus and other clinical parameters. Findings: The model for diagnosing the status of RCT produced an AUC of 0.989 (95%CI: 0.954-0.999) in the training cohort and 0.979 (95% CI: 0.906-0.999) for the validation cohort. Four highest mRMR-ranked features were selected to construct the RCT model. The MRI signature markers, based on features extracted from the humerus, supraspinatus, and infraspinatus yielded average AUC of 0.662±0.054,0.673±0.089,0.879±0.041 for training sets and 0.600±0.064, 0.673±0.089, 0.739±0.069 for validation sets. The model based on multiple regions of interests produced an AUC of 0.923±0.017 for the training dataset and 0.790±0.082 for the validation dataset. The nomogram combining integrated features and clinical factors yielded an AUC of 0.961±0.020 for the training dataset and 0.808±0.081 for the validation dataset, which displayed the best performance among all models. Interpretation: Our study validated two models for the diagnosis of rotator cuff tear and prediction of post-operative re-tear respectively. The RCT model had a favorable performance in diagnosis, while the combined nomogram based on radiomics score and clinical factors yielded a decent prediction accuracy of re-tear. Both models are anticipated to provide valuable information for clinical decision-making in the future. Funding Statement: This work was supported by the National Natural Science Foundation (81874019). Declaration of Interests: All authors declare that they have no conflicts of interest. Ethics Approval Statement: This retrospective study was approved by the Institutional Review Board of the Second Affiliated Hospital, Zhejiang University School of Medicine (Zhejiang, China). The signed informed consent forms were waived. This study was conducted according to the Declaration of Helsinki.

Hypoxia‐inducible factor 1α (HIF‐1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF‐1α is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF‐1α in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF‐1α in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF‐1α, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF‐1α was increased in the DRG of occluded limbs (optical density: 0.89 ± 0.13 in control versus 1.5 ± 0.05 in occlusion; p 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF‐1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion.

High-fidelity and controllable optical cloning of high-dimensional (high-D) optical beams is very important for the development of novel techniques for optical imaging, lithography, and communications, etc. Here we propose a scheme to realize the cloning of high-D optical beams with a Rydberg atomic gas via electromagnetically induced transparency. We show that strong atom-atom interaction can map to two probe laser fields, which may acquire giant nonlocal Kerr nonlinearities supporting the formation of stable high-D optical solitons and vortices at very low light power. We also show that such optical solitons and vortices prepared in one probe field can be cloned onto another one with high fidelity, and the cloning may be actively manipulated through the tuning of the nonlocality degree of the Kerr nonlinearities. Moreover, we demonstrate that based on such a cloning scheme multitimes and multicomponents cloning of high-D optical beams are also possible, which allows us to acquire multiple copies of high-D optical beams. The results on the optical cloning reported here are not only of fundamental interest for nonlocal nonlinear optics but also promising for practical applications in optical information processing and transmission.

Processing satellite signals can deceive receiver time. For GPS time receivers, this paper proposes two time spoofing methods, one is based on delay control, and the other is based on clock frequency control. By analyzing the principle of satellite timing, the receiver's time-related parameters and time spoofing principle are deduced and the delay control model and the clock control model are constructed respectively. Finally, the effectiveness of the two control methods is verified through design simulation experiments, of which results present that the time-delay control method can linearly skew the receiver time and the clock control method makes the receiver time shift at a certain speed.

The purpose of this study was to determine the effects of one-time acute heat treatment (HT) on the exaggerated exercise pressor reflex in a model of peripheral arterial insufficiency induced by ligation of the femoral artery and was to further examine the underlying mechanism of ATP-P2X3 signal activity during this process. The blood pressure (BP) response to static muscle contraction and muscle tendon stretch was recorded to determine the exercise pressor reflex. Also, αβ-methylene ATP (αβ-me ATP) was injected into the arterial blood supply of the hindlimb muscles to stimulate P2X3 receptors in the muscle afferent nerves. To process one-time acute HT, a heating pad was placed locally on the hindlimb and the muscle temperature (Tm) was increased by ~1.5°C and maintained for 5 min. Compared with control rats, a greater mean arterial pressure (MAP) response to muscle contraction was observed in rats with femoral occlusion in a pre-heat control session (28 ± 2 mmHg in occluded rats/n = 12 vs. 18 ± 2 mmHg in control rats/n = 9; p < 0.05). The one-time acute HT attenuated the amplification of the BP response in rats with femoral artery occlusion (MAP response: 19 ± 8 mmHg in occluded rats + HT/n = 11; p < 0.05 vs. occluded rats). In contrast, HT did not significantly attenuate amplification of MAP response to muscle stretch and αβ-me ATP injection in rats with femoral artery occlusion and controls (all p > 0.05). Our data suggest that one-time acute HT selectively attenuates the amplified pressor response induced by activation of the metabolic and mechanical components of the reflex in rats after femoral artery occlusion. The suppressing effects of acute HT on the exaggerated exercise pressor reflex are likely mediated through a reduction in metabolites (e.g., ATP) stimulating the muscle afferent nerves in contracting muscle, but unlikely through direct alteration of P2X receptors per se.

Background IL-27 attenuates allergic inflammation and improves lung function in mouse models of allergic asthma. However, plasma IL-27 levels of asthma patients and the association with clinical features remain poorly understood. Methods This study examined plasma IL-27 protein expression in untreated asthma patients and controls, analyzed its correlation with Th2 inflammation and lung function, and evaluated the effect of corticosteroids on IL-27 expression. Results Plasma IL-27 levels were lower in untreated asthma patients compared to controls. Plasma IL-27 levels were inversely correlated with sputum IL-5 mRNA expression in Th2Hi group. The Th2HiIL-27Low subgroup suffered from the highest airway hyperresponsiveness (AHR) and the worst pulmonary function. The patients in Th2LowIL-27Low subgroup were less likely to be atopic and had the worst improvement of symptoms after four weeks of standard treatment. In vitro, dexamethasone could decrease the expression of IL-27 in THP-1 cell line. The majority of asthma patients had further decreased IL-27 levels after standard treatment, whereas patients with sustained high levels of IL-27 post-treatment had more blood neutrophils at baseline compared with those without. Conclusions The results indicate that low levels of IL-27 in peripheral blood are closely related to Th2 inflammation and lung function of asthma patients. Low IL-27 levels in combination with high Th2 inflammation identify an asthma phenotype with high AHR and substantial response to corticosteroids. Understanding of this interaction could help to elucidate the inherent inflammation heterogeneity of asthma.

Background: Cognitive impairments in temporal lobe epilepsy (TLE) patients has been described as a chronically progressive feature of the disease. However, how severe recurrent seizures modify neuronal circuits in the human brain and subsequently degrade cognitive function, remains largely unknown. Here, we aimed to investigate longitudinal alterations by functional magnetic resonance imaging (fMRI) in TLE patients and to assess how those alterations are related to cognitive function performance. Methods: Sixteen TLE patients and 20 normal controls (NCs) were recruited for a study to observe longitudinal alterations in resting-state functional connectivity (FC) and to estimate alertness, orientation, and executive function both at baseline and at a follow-up time ~3 years later. Results: TLE patients, compared with NCs, showed impaired executive function, intrinsic alertness, and phasic alertness and exhibited lengthened reaction time (RT) in the spatial cue and center cue conditions at baseline. The orienting function of TLE patients was declined at follow-up compared to the baseline. Cross-sectional analysis demonstrated that TLE patients displayed significantly greater positive correlation than NCs between the right dorsolateral prefrontal cortex (DLPFC) and the right inferior parietal lobule (IPL) and right superior frontal gyrus (SFG). Furthermore, among TLE patients, the longitudinal study revealed a decrease in correlation between the right DLPFC and the right SFG compared to the baseline. In addition, there was a significant negative correlation between the longitudinal change in FC and the change in orienting function in TLE subjects. Conclusions: Abnormal connectivity between the DLPFC and the SFG suggests the potential of longitudinal resting-state fMRI to delineate regions relevant to cognitive dysfunction for disease progression.

Background: Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease. Reports of rare cases of PAP due to Pneumocystis jirovecii (P. jirovecii) exist in infants with immunodeficiency diseases, but no cases have been reported to date in pediatric patients with type 1 hyper-IgM syndrome (HIGM1). Case Presentation: Herein, we present a case of PAP secondary to P. jirovecii on an infant with HIGM1. He was admitted to our unit because of cough and tachypnea. Lung biopsy confirmed the diagnosis of PAP, whereas hexamine-silver staining of the bronchoalveolar lavage fluid identified P. jirovecii infection. No other probable cause of PAP was observed. Whole exome sequencing indicated a novel c.511dupA (p.I171N*30) hemizygous mutation in the CD40 ligand (CD40LG) gene. He was cured with bronchoalveolar lavage and compound sulfamethoxazole tablets. Conclusions: To our knowledge, this is the first reported case of P. jirovecii infection as a reversible cause of PAP in an infant with HIGM1.

Background: Since December 2019, coronavirus disease 2019 (COVID-19), as an infectious disease with cytokine storm, has become an emerging global challenge. To assess the duration of SARS-COV-2 viral shedding and associated risk factors in COVID-19 patients.Methods: COVID-19 patients with interleukin (IL)-1b, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α cytokines data consecutively admitted to Tongji Hospital from January 27, 2020 through February 5, 2020 were enrolled and been followed up until March 24, 2020. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to assess the duration of viral shedding and risk factors affecting virus clearance.Results: 246 inpatients with laboratory confirmed COVID-19 were enrolled. The median duration of viral shedding was 24 days, ranging from 6 to 63 days. Age, severity of COVID-19, albumin, lactate dehydrogenase (LDH), D-dimer, ferritin and sIL-2R were associated with duration of viral shedding. Administration of lopinavir-ritonavir, arbidol, oseltamivir and intravenous immunoglobulin did not shorten viral shedding time. Multivariate cox regression analysis revealed that sIL-2R, LDH and severity of COVID-19 were independent factors associated with duration of viral shedding. At stratified analysis, the viral shedding time was positively correlated with age, sIL-2R and LDH in non-corticosteroid subgroup, while negatively correlated with lymphocyte count in corticosteroid group. Conclusions: The present study demonstrated that elevated sIL-2R, increased LDH and severe status were related to prolongation of viral shedding in COVID-19 inpatients. Further research is urgent to investigate the mechanism of immune reaction involved in the virus clearance process and aim to the optimal antiviral therapy.

Background The rapid outbreak of coronavirus disease 2019 (COVID-19) has turned into a public health emergency of international concern. Epidemiological research has shown that sex is associated with the severity of COVID-19, but the underlying mechanism of sex predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID-19. Methods In this retrospective study, we enrolled 548 COVID-19 inpatients from Tongji Hospital from 26 January to 5 February 2020, and followed up to 3 March 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. The Cox proportional hazard regression model was applied to identify the gendered effect on mortality of COVID-19 after adjusting for age, comorbidity, and smoking history. The multiple linear regression method was used to explore the influence of sex on inflammation reaction. Results Males had higher mortality than females did (22.2% vs 10.4%), with an hazard ratio of 1.923 (95% confidence interval, 1.181-3.130); elder age and comorbidity were significantly associated with decease of COVID-19 patients. Excess inflammation reaction was related to severity of COVID-19. Male patients had greater inflammation reaction, with higher levels of interleukin 10, tumor necrosis factor-α, lactose dehydrogenase, ferritin, and hyper-sensitive C-reactive protein, but a lower lymphocyte count than females adjusted by age and comorbidity. Conclusions Sex, age, and comorbidity are critical risk factors for mortality of COVID-19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males, especially elder males, to develop a cytokine storm, causing potential acute respiratory distressed syndrome, multiple organ failure and decease.