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Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy. Currently, there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury. Here, we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide, which can protect against hypoxic injury in adulthood, in a mouse model of neonatal hypoxic-ischemic brain injury. In this study, nicotinamide adenine dinucleotide (5 mg/kg) was intraperitoneally administered 30 minutes before surgery and every 24 hours thereafter. The results showed that nicotinamide adenine dinucleotide treatment improved body weight, brain structure, adenosine triphosphate levels, oxidative damage, neurobehavioral test outcomes, and seizure threshold in experimental mice. Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice. Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine (or cysteine) peptidase inhibitor, clade A, member 3N, fibronectin 1, 5′-nucleotidase, cytosolic IA, microtubule associated protein 2, and complexin 2. Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways (e.g., nuclear factor-kappa B, mitogen-activated protein kinase, and phosphatidylinositol 3 kinase/protein kinase B). These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

Vertical gardens have become important strategies for urban heat island migration in recent years. However, the simulation tools for green façade (GF) with climbing plants coupling the shading and wind-induced effects are still lacked. This study focused on GF effects on human thermal comfort (HTC) optimization in a transitional space. The main purpose was to develop a couple method on HTC simulations. Field measurements in a hot-humid climate area were conducted to obtain the parameters of GF foliage layers. A couple simulation method with Ansys Fluent, Ladybug, and Honeybee tools was developed. Seven GFs layouts on a standard balcony model were simulated. In field measurements, the Ave. global irradiation was reduced by 73.29%, leaf area index was measured at 1.56–3.61, and foliage cover ratio was measured at 49.74–92.88%. In the simulations, the results of the Ave. wind velocity were reduced by 0.20–0.77 m s−1, the Ave. air temperature was reduced by 0.2°C, the Ave. mean radiant temperature was reduced by 0.5–7°C, and the Ave. physiological equivalent temperature was reduced by 0.3–3.2°C. The couple method could support the architectural and landscape design integrating with the GFs in future.

Climate change has increased the intensity and frequency of seasonal droughts, which could fundamentally affect the terrestrial carbon (C) cycle. However, as the second-largest terrestrial C flux, soil respiration (Rs) and its heterotrophic (Rh) and autotrophic (Ra) components in response to seasonal drought are unclear. To investigate the effect of seasonal drought on the patterns and mechanisms of Rs and its components, a two-year continuous Rs measurement experiment was conducted in typical rain-fed managed alfalfa (Medicago sativa L.) fields on the Loess Plateau in China. The results showed that the ranges of Rs, Rh and Ra in the four seasons of managed alfalfa fields on the Loess Plateau were 0.45–3.70, 0.13–2.27, and 0.33–2.14 μmol m−2 s−1, respectively. There was no significant difference in the average annual Rs between the two years (P > 0.05). Both spring and summer droughts significantly decreased Rs; however, the seasonal Rh and Ra had different patterns under spring and summer droughts. Spring drought significantly reduced the seasonal Rh by 35.19 % but increased Ra by 20.35 %. In contrast, summer drought significantly increased the seasonal Rh by 45.51 % but decreased the Ra by 35.05 %. The differential response of Ra to seasonal drought was attributed to the opposite responses of the leaf area index (LAI) and photosynthetic rate to spring and summer drought, while Rh was related to the contrasting microorganism responses to spring drought and the pulse effect of rainfall following summer drought. Our study highlights the contrasting responses of Ra and Rh to seasonal drought. Spring drought significantly reduced the relative contribution of Rh to Rs, but summer drought increased the relative contribution of Rh to Rs. These results suggest that future increases in the frequency of summer droughts may accelerate the turnover of soil C and further affect the stability of soil C stocks in semi-arid regions.

Cytoplasmic dynein is an important intracellular motor protein that plays an important role in neuronal growth, axonal polarity formation, dendritic differentiation, and dendritic spine development among others. The intermediate chain of dynein, encoded by Dync1i1, plays a vital role in the dynein complex. Therefore, we assessed the behavioral and related neuronal activities in mice with dync1i1 gene knockout. Neuronal activities in primary somatosensory cortex were recorded by in vivo electrophysiology and manipulated by optogenetic and chemogenetics. Nociception of mechanical, thermal, and cold pain in Dync1i1−/− mice were impaired. The activities of parvalbumin (PV) interneurons and gamma oscillation in primary somatosensory were also impaired when exposed to mechanical nociceptive stimulation. This neuronal dysfunction was rescued by optogenetic activation of PV neurons in Dync1i1−/− mice, and mimicked by suppressing PV neurons using chemogenetics in WT mice. Impaired pain sensations in Dync1i1−/− mice were correlated with impaired gamma oscillations due to a loss of interneurons, especially the PV type. This genotype-driven approach revealed an association between impaired pain sensation and cytoplasmic dynein complex.

Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder leading to cognitive impairment in the elderly, and no effective treatment exists. Increasing evidence has demonstrated that physical therapy and electroacupuncture (EA) effectively improve spatial learning and memory abilities. Nevertheless, the mechanism underlying the effects of EA on AD pathology is largely unexplored. Acupuncture at Zusanli (ST 36) has previously been shown to improve cognitive impairment in AD, but the mechanism is unclear. According to recent studies, EA drives the vagal–adrenal axis from the hindlimb ST 36 acupoint but not from the abdominal Tianshu (ST 25) to curb severe inflammation in mice. This study examined whether ST 36 acupuncture improves cognitive dysfunction in AD model mice by improving neuroinflammation and its underlying mechanism. Methods: Male 5xFAD mice (aged 3, 6, and 9 months) were used as the AD animal model and were randomly divided into three groups: the AD model group (AD group), the electroacupuncture at ST 36 acupoint group (EA-ST 36 group), and the electroacupuncture at ST 25 acupoint group (EA-ST 25 group). Age-matched wild-type mice were used as the normal control (WT) group. EA (10 Hz, 0.5 mA) was applied to the acupoints on both sides for 15 min, 5 times per week for 4 weeks. Motor ability and cognitive ability were assessed by the open field test, the novel object recognition task, and the Morris water maze test. Thioflavin S staining and immunofluorescence were used to mark Aβ plaques and microglia. The levels of NLRP3, caspase-1, ASC, interleukin (IL)-1β, and IL-18 in the hippocampus were assayed by Western blotting or qRT-PCR. Results: EA at ST 36, but not ST 25, significantly improved motor function and cognitive ability and reduced both Aβ deposition and microglia and NLRP3 inflammasome activation in 5×FAD mice. Conclusion: EA stimulation at ST 36 effectively improved memory impairment in 5×FAD mice by a mechanism that regulated microglia activation and alleviated neuroinflammation by inhibiting the NLRP3 inflammatory response in the hippocampus. This study shows that ST 36 may be a specific acupoint to improve the condition of AD patients.

Many applications suitable for multicast transmission, such as video conferencing and live e-commerce, demand high Quality of Service (QoS) and require data delivery to be completed within specified delay constraints. Some methods have been proposed for constructing delay-constrained multicast routing based on network state. However, obtaining precise network latency can be challenging, resulting in inaccuracies in delay-constrained routing calculations and, ultimately, the inability to meet application requirements. Additionally, many methods engage in an indiscriminate exploration of potential paths in the network, causing significant message processing overhead. This paper proposes an Information-Centric Networking (ICN)-based approach for delay-constrained multicast routing. Our method dynamically constructs multicast paths from tree nodes to receivers based on real-time path status detection during the join message propagation phase. Additionally, we present a method for acquiring neighborhood state information to facilitate real-time routing decisions. To curtail indiscriminate path exploration, our approach uses the ICN Name Resolution System (NRS) to obtain and select potential optimal tree nodes. For this purpose, we design a multicast service registration and resolution mechanism using the ICN Name Resolution System (NRS). Simulation results indicate that our approach exhibits a higher success ratio and concurrently incurs lower message processing overhead than some other methods, particularly in situations with stringent delay constraints.

The control of transmission rates is currently a major topic in network research, as it plays a significant role in determining network performance. Traditional network design principles suggest that network nodes should only be responsible for forwarding data, while the sending node should manage control. However, sending nodes often lack information about network resources and must use slow-start algorithms to increase the transmission rate, potentially leading to wasted bandwidth and network congestion. Furthermore, incorrect judgments about network congestion by sending nodes may further reduce network throughput. The emergence of new Internet architectures, such as information-centric networks (ICNn), has empowered network nodes with more capabilities, including computation and caching. This paper proposes a method for transmission rate control that actively avoids congestion through network node bandwidth allocation. The sending, network, and receiving nodes each calculate the available transmission rate, and the sending node negotiates with the other nodes through a rate negotiation message to obtain the maximum transmission rate possible given the current state of the network. The network nodes notify the sending node to adjust the transmission rate to adapt to changes in the network through a rate adjustment message. Simulation experiments show that the proposed method is better than traditional methods in reducing network congestion, providing a stable transmission rate, increasing the network throughput capacity, and improving performance in high-latency and high-bandwidth networks. Additionally, the proposed transmission rate control method is fairer than traditional methods.

Aerial manipulator systems possess active operational capability, and by incorporating various sensors, the systems’ autonomy is further enhanced. In this paper, we address the challenge of accurate positioning between an aerial manipulator and the operational targets during tasks such as grasping and delivery in the absence of motion capture systems indoors. We propose a vision-guided aerial manipulator system comprising a quad-rotor UAV and a single-degree-of-freedom manipulator. First, the overall structure of the aerial manipulator is designed, and a hierarchical control system is established. We employ the fusion of LiDAR-based SLAM (simultaneous localization and mapping) and IMU (inertial measurement unit) to enhance the positioning accuracy of the aerial manipulator. Real-time target detection and recognition are achieved by combining a depth camera and laser sensor for distance measurements, enabling adjustment of the grasping pose of the aerial manipulator. Finally, we employ a segmented grasping strategy to position and grasp the target object precisely. Experimental results demonstrate that the designed aerial manipulator system maintains a stable orientation within a certain range of ±5° during operation; its position movement is independent of orientation changes. The successful autonomous grasping of lightweight cylindrical objects in real-world scenarios verifies the effectiveness and rationality of the proposed system, ensuring high operational efficiency and robust disturbance resistance.

Background: Ischemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD+) and butylphthalide (NBP) on in vitro and in vivo ischemic stroke models.Methods: Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cerebral infarct volume, neurobehavioral indices, antioxidant activity, ATP level and lactic acid content were determined. The neuroprotective effects of NAD+ or NBP were compared using sirtuin inhibitor niacinamide (NAM).Results: Intraperitoneal injection of NBP within 4 h or intravenous injection of NAD+ within 1 h after t-MCAO/R significantly reduced the volume of infarcts, cerebral edema, and neurological deficits. Administration of NAD+ and NBP immediately after t-MCAO/R in mice showed similar neuroprotection against acute and long-term ischemic injury. Both NAD+ and NBP significantly inhibited the accumulation of MDA and H2O2 and reduced oxidative stress. NAD+ was superior to NBP in inhibiting lipid oxidation and DNA damage. Furthermore, although both NAD+ and NBP improved the morphology of mitochondrial damage induced by ischemia/reperfusion, NAD+ more effectively reversed the decrease of ATP and increase of lactic acid after ischemia/reperfusion compared with NBP. NAD+ but not NBP treatment significantly upregulated SIRT3 in the brain, but the sirtuin inhibitor NAM could abolish the protective effect of NAD+ and NBP by inhibiting SIRT1 or SIRT3.Conclusions: These results confirmed the protective effects of NAD+ and NBP on cerebral ischemic injury. NBP and NAD+ showed similar antioxidant effects, while NAD+ had better ability in restoring energy metabolism, possibly through upregulating the activity of SIRT1 and SIRT3. The protection provided by NBP against cerebral ischemia/reperfusion may be achieved through SIRT1.

ObjectiveTo investigate the characteristic changes in the gut microbiota of patients with type A aortic dissection (AAD) and provide a theoretical basis for future microbiome-oriented interventional studies.MethodsHigh-throughput 16S rDNA sequencing was performed on the stool samples of patients with and without (healthy control subjects) AAD. Using alpha and beta diversity analysis, we compared the gut microbiota composition of 20 patients with AAD and 20 healthy controls matched for gender, age, BMI, and geographical region. The accuracy of AAD prediction by differential microbiome was calculated using the random forest machine learning model. Targeted measurement of the plasma concentration of short-chain fatty acids (SCFAs), which are the main metabolites of the gut microbiome, was performed using gas chromatography–mass spectrometry (GC–MS). Spearman’s correlation analysis was conducted to determine the relationships of gut microbiome and SCFAs with the clinical characteristics of subjects.ResultsThe differences in gut microbiota alpha diversity between patients with AAD and the healthy controls were not statistically significant (Shannon index: p = 0.19; Chao1: p = 0.4); however, the microbiota composition (beta diversity) was significantly different between the two groups (Anosim, p = 0.001). Bacteroidota was enriched at the phylum level, and the SCFA-producing genera Prevotella, Porphyromonas, Lachnospiraceae, and Ruminococcus and inflammation-related genera Fenollaria and Sutterella were enriched at the genus level in the AAD group compared with those in the control group. The random forest model could predict AAD from gut microbiota composition with an accuracy of 87.5% and the area-under-curve (AUC) of the receiver operating characteristic curve was 0.833. The SCFA content of patients with AAD was higher than that of the control group, with the difference being statistically significant (p

Abstract Background Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention. Methods Using Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment. Results We demonstrated that Cx3cr1CreERIL-10−/− mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium-binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreERIL-10−/− mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The co-localization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus. Conclusions The results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/− mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation. Graphical Abstract

Information-Centric Networking (ICN) has revolutionized the manner of content acquisition by shifting the communication mode from host-centric to information-centric. Considering the existing, large amount of IP infrastructure in current networks, the new ICN architecture is proposed to be compatible with existing networks in order to reduce deployment cost. However, due to compatibility with IP networks, ICN data packets must be transmitted through the default path provided by IP routing regulations, which also limits the transmission efficiency and reliability of ICN. In order to address this issue, this paper introduces a multipath transmission method applied in ICN which takes full advantage of the functions and characteristics of ICN and builds multiple end-to-end relay paths by using the ICN routers as relay nodes. We then propose a relay-node-selection algorithm based on path correlation to minimize the impact of overlapping links. Moreover, we comprehensively calculate the path state value by combining the round-trip time and packet loss rate and propose a multipath data-scheduling algorithm based on the path state value. Simulation experiments show that the proposed method can maintain high bandwidth utilization while reducing the number of out-of-order packets.

As the Internet communication model changes from host-centric to content-centric, information-centric networking (ICN) as a new network architecture has received increasing attention. There are often multiple replicas of content in ICN, and how to reasonably utilize the characteristics of multiple replicas to further improve user experience is an important issue. In this paper, we propose a replica-selection algorithm, called the transmission completion time estimation (TCTE) algorithm. TCTE maintains the state of replica nodes in the domain with passive measurements in a limited domain of an enhanced name resolution system (ENRS), then estimates the transmission completion time of different replica nodes and selects the smallest one. When no replica is found in the ENRS domain, the nearest-replica algorithm will be used, so TCTE will not increase the traffic in the core network. Experiments show that TCTE not only effectively improves the user’s download rate and edge node throughput, reduces download rate fluctuations, reduces user download delay, and improves fairness, but also has universal applicability.

Due to the overload of IP semantics, the traditional TCP/IP network has a number of problems in scalability, mobility, and security. In this context, information-centric networking (ICN) is proposed to solve these problems. To reduce the cost of deployment and smoothly evolve, the ICN architecture needs to be compatible with existing IP infrastructure. However, the rigid underlying IP routing regulation limits the data transmission efficiency of ICN. In this paper, we propose a novel multipath transmission scheme by utilizing the characteristics and functions of ICN to enhance data transmission. The process of multipath transmission can be regarded as a service, and a multipath transmission service ID (MPSID) is assigned. By using the ICN routers bound to the MPSID as relay nodes, multiple parallel paths between the data source and the receiver are constructed. Moreover, we design a path management mechanism, including path selection and path switching. It can determine the initial path based on historical transmission information and switch to other optimal paths according to the congestion degree during transmission. The experimental results show that our proposed method can improve the average throughput and reduce the average flow completion time and the average chunk completion time.

Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.

Hypoxia-ischemia (HI) is the most common acute brain threat in neonates and a leading cause of neurodevelopmental impairment. Exploring the new molecular mechanism of HI brain injury has important clinical translational significance for the next clinical intervention research. Lipid phosphatase-related proteins (PLPPRs) are regulators of mitochondrial membrane integrity and energy metabolism. We recently found that Plppr5 knockout exacerbated HI impairment in some aspects and partially attenuated the neuroprotective effects of melatonin, suggesting that Plppr5 may be a novel intervention target for HI. The present study aimed to determine the long-term effects of gene knockout of Plppr5 on HI brain injury, focusing on the neuronal excitability phenotype, and to determine the effect of Plppr5 gene silencing on neuronal zinc metabolism and mitochondrial function in vitro. 10-day-old wild type (WT) mice and Plppr5-deficient (Plppr5–/–) mice were subjected to hypoxia-ischemia. Lesion volumes and HI-induced neuroexcitotoxic phenotypes were quantified together with ZnT1 protein expression in hippocampus. In addition, HT22 (mouse hippocampal neuronal cells) cell model was established by oxygen–glucose deprivation/reoxygenation (OGD/R) treatment and was treated with medium containing LV-sh_Plppr5 or control virus. Mitochondrial oxidative stress indicator ROS, mitochondrial ZnT1 protein expression and zinc ion content were detected.ResultsPlppr5-deficient mice subjected to hypoxia-ischemia at postnatal day 10 present significantly higher cerebral infarction. Plppr5-deficient mice were endowed with a more pronounced superexcitability phenotype at 4 weeks after HI, manifested as a reduced seizure threshold. ZnT1 protein was also found reduced in Plppr5-deficient mice as well as in mice subjected to HI excitotoxicity. Plppr5 knockout in vivo exacerbates HI brain injury phenotypes, including infarct volume and seizure threshold. In addition, knockout of the Plppr5 gene reduced the MFS score to some extent. In vitro Plppr5 silencing directly interferes with neuronal zinc metabolism homeostasis and exacerbates hypoxia-induced mitochondrial oxidative stress damage. Taken together, our findings demonstrate for the first time that Plppr5-deficient mouse pups exposed to neuronal hypoxia and ischemia exhibit aggravated acute brain injury and long-term brain excitability compared with the same treated WT pups, which may be related to the disruption of zinc and mitochondria-dependent metabolic pathways in the hippocampus. These data support further investigation into novel approaches targeting Plppr5-mediated zinc and mitochondrial homeostasis in neonatal HIE.

RET rearrangements are rare, and occur in 1%-2% of all non-small cell lung cancer (NSCLC) patients. Pralsetinib has a significant anti-tumor effect in patients with advanced NSCLC and a RET rearrangement. Previous studies have confirmed the efficiency of neoadjuvant target therapy for NSCLC. Herein we present a case involving a female patient who was diagnosed with stage IIIA lung adenocarcinoma and harbored a KIF5B-RET rearrangement based on next-generation sequencing. Radiologic downstaging was indicated after pralsetinib treatment. Therefore, a right lower lobectomy and systemic lymphadenectomy were successfully performed. The postoperative pathologic results revealed a response rate of 74% for primary tumor and no residual viable tumor cells were observed in lymph nodes. The tumor, nodes, and metastases (TNM) stage was ypT1cN1M0. The tumor micro-environment (TME) of the primary tumor was also assessed.

Background: Medication adherence is crucial for patients with mechanical heart valve replacement. Although families functioning is positively associated with medication adherence, little is known about the underlying mechanisms.Objective: To test whether family functioning affects medication adherence through illness perceptions and whether this mediating effect was moderated by medication literacy.Methods: 319 patients after mechanical heart valve replacement were included in this cross-sectional study from June 2021 to October 2021. Data regarding family functioning, illness perceptions, medication adherence, and medication literacy were collected through questionnaires. The moderated mediation model was examined by Hayes’s PROCESS macro, based on the bootstrapping method.Results: The results revealed illness perceptions partially mediated the association of family functioning on medication adherence [β = 0.08, 95% confidence intervals: (0.04, 0.12)], and this effect was stronger for patients with low medication literacy than those with high literacy [β = −0.36, 95% CI: (−0.50, −0.22)]. Furthermore, the relationship between family functioning and medication adherence was only significant in patients with low medication literacy [β= 0.36, 95% CI: (0.23, 0.50)].Conclusion: The mediating effect of illness perceptions between family functioning and medication adherence was moderated by medication literacy. Efforts to improve medication adherence by targeting at improving family functioning may be more effective when considering illness perceptions, especially for patients with limited medication literacy.

Software-defined network separates the control plane and the data plane, making the network more flexible. With the expansion of the network scale, one centralized controller cannot meet the latency needs of large-scale networks. Therefore, it is necessary to use multicontroller architecture, which has some problems with the controller placement. In this article, we take both the average latency and the worst latency between switch and controller into consideration and make a multi-objective optimization model. An improved label propagation algorithm based on traffic gravitation is proposed to solve the subdomain division problem, and a heuristic method is for subdomain controller placement. The simulation experiments show the effectiveness of the proposed algorithm and the time complexity guarantee for large-scale networks.

Abstract Background Many studies have shown an association of childhood respiratory diseases with short-term temperature variability such as diurnal temperature range (DTR) and temperature change between two neighboring days (TCN). However, the impact of temperature variability on allergic rhinitis (AR) has not been investigated so far. This study sought to evaluate the short-term effect of temperature variability (i.e., TCN and DTR) on AR, as well as to identify vulnerable subpopulations. Method We collected daily data on emergency room visits and outpatients for AR and weather variables in Hefei, China during 2014–2016. A distributed lag non-linear model that controlled for long-term trend and seasonality, mean temperature, relative humidity, day of week was used to fit the associations of AR with DTR and TCN. Stratified analyses by age, sex and occupation were also performed. Results During the study period, there were a total of 53,538 cases and the average values of DTR and TCN were 8.4 °C (range: 1.0 °C to 21.2 °C) and 0 °C (range: − 12.2 °C to 5.9 °C), respectively. While we did not observe an adverse effect of DTR on AR, TCN was significantly associated with increased risk of AR. Specifically, a large temperature drop between two adjacent days (3.8 °C, 5th percentile of TCN) has a delayed and short-lasting effect on AR, with the estimated relative risk of 1.02 (95% confidence interval: 1.01 to 1.04) at lag 12. Moreover, boys and children older than 15 years seemed to be more vulnerable to the effect of TCN. Conclusions This study provided evidence of an adverse effect of large temperature drops between two adjacent days on childhood AR. Attention paid to boys and older children may help prevent AR attacks.

Background: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear.Method: The expression levels of LRMP mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas. In vitro experiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships among LRMP, LRMP co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0.Results: The expression of LRMP was significantly lower in LUAD tissues and cell lines. High LRMP expression is associated with a better prognosis in patients with LUAD. In vitro experimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints.Conclusions: Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.

IntroductionEpileptogenesis is understood as the plastic process that produces a persistent reorganization of the brain’s neural network after a precipitating injury (recurrent neonatal seizures, for instance) with a latent period, finally leading to neuronal hyperexcitability. Plasticity-related genes (PRGs), also known as lipid phosphate phosphatase-related proteins (PLPPRs), are regulators of mitochondrial membrane integrity and energy metabolism. This study was undertaken to determine whether PRG5 gene knockout contributes to the delayed hypersensitivity induced by developmental seizures and the aberrant sprouting of hippocampal mossy fibers, and to determine whether it is achieved through the mitochondrial pathway. Here, we developed a “twist” seizure model by coupling pilocarpine-induced juvenile seizures with later exposure to penicillin to test the long-term effects of PRG5 knockout on seizure latency through comparison with wild-type (WT) mice. Hippocampal mossy fiber sprouting (MFS) was detected by Timm staining. In order to clarify the mechanism of the adverse reactions triggered by PRG5 knockout, hippocampal HT22 neuronal cultures were exposed to glutamate, with or without PRG5 interference. Mitochondrial function, oxidative stress indicators and zinc ion content were detected.ResultsPRG5 gene knockout significantly reduced the seizure latency, and aggravated the lowered seizure threshold induced by developmental seizures. Besides, knockout of the PRG5 gene reduced the MFS scores to a certain extent. Furthermore, PRG5 gene silencing significantly increases the zinc ion content in hippocampal neurons, impairs neuronal activity and mitochondrial function, and exacerbates glutamate-induced oxidative stress damage.ConclusionIn summary, PRG5 KO is associated with significantly greater hypersusceptibility to juvenile seizures in PRG5(–/–) mice compared with WT mice. These effects may be related to the hippocampal zinc signaling. The effects do not appear to be related to changes in MFS because KO mice with juvenile seizures had the shortest seizure latencies but exhibited less MFS than WT mice with juvenile seizures.

Abstract Background Diagnostic value of procalcitonin (PCT) for acute appendicitis (AA) has been evaluated in adult patients, but the application in children remains controversial. The aim of this study was to evaluate the diagnostic value of PCT for overall and complicated AA in children. Methods The PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Chinese National Knowledge Infrastructure, and Wanfang were searched along with reference lists of relevant articles up to January 2018 without language restrictions. Original articles that reported the performance of PCT in the diagnosis of pediatric AA and associated complications were selected. To assess the diagnostic value of PCT, sensitivity, specificity, diagnostic odds ratios (DORs), summary receiver operating characteristic (ROC) curves, area under the curve (AUC), and 95% confidence intervals (95% CIs) were estimated. Results Seven qualifying studies (504 confirmed AA and 368 controls) from 6 countries for overall AA and 4 studies (187 complicated AA and 185 uncomplicated AA) for complicated AA from 3 countries were identified. The pooled sensitivity and specificity of PCT for the diagnosis of pediatric AA were 0.62 (95% CI: 0.57–0.66) and 0.86 (95% CI: 0.82–0.89), respectively. The DOR was 21.4 (95% CI: 3.64–126.1) and the AUC was 0.955. PCT was more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 0.89 (95% CI: 0.84–0.93), specificity of 0.90 (95% CI: 0.86–0.94), and DOR of 76.73 (95% CI: 21.6–272.9). Conclusion This meta-analysis showed that PCT may have potential value in diagnosing pediatric AA. Moreover, PCT had greater diagnostic value in identifying pediatric complicated appendicitis.

As a representative of lightweight virtualization, container technology has been widely used in cloud services and edge computing applications. However, in the resource pool scenario composed by multiple intelligent terminal devices, considering the limited resources and poor stability of these devices, it is necessary to split the overall service into multiple microservices and deploy the backups of them in respective containers. Traditional container scheduling policies tend to be less effective in solving such problems. Therefore, the article used a meta-heuristic algorithm to solve this kind of problems. Based on a newly proposed salp swarm algorithm (SSA), the paper presented a comprehensive improved SSA (CISSA). CISSA improved the performance of the original SSA by 4 steps. To verify the performance of CISSA in different kinds of test functions, the algorithm was compared with 7 commonly-used meta-heuristic algorithms in 29 benchmark functions provided by the author of SSA. In addition, the article constructed three container cluster models of different sizes, all these algorithms were used to solve these redundant container deployment problems, the experimental results indicate that the CISSA is superior to other algorithms in such problems of different dimensions.

The present study investigated the mediating role of negative emotion in the relationship between cybervictimization and non-suicidal self-injury (NSSI), and the moderating role of friendship quality in the indirect relationship. This model was tested with 1,326 Chinese adolescents who suffered from cyberbullying in the last 1 year; 727 were boys and 591 were girls, and their mean age was 13.67 years (SD = 1.34, range 11–17). Participants filled out questionnaires regarding cybervictimization, negative emotion, friendship quality, and non-suicidal self-injury. After demographic variables were controlled, cybervictimization was significantly positively associated with non-suicidal self-injury. Mediation analysis revealed that negative emotion partially mediated the association between cybervictimization and non-suicidal self-injury. Moderated mediation analysis further indicated that the mediated path was weaker for adolescents with higher levels of friendship quality. These findings underscore the importance of identifying the mechanisms that moderate the mediated path between cybervictimization and non-suicidal self-injury among adolescents.

Cerebral palsy (CP), a group of clinical syndromes caused by non-progressive brain damage in the developing fetus or infant, is one of the most common causes of lifelong physical disability in children in most countries. At present, many researchers believe that perinatal cerebral hypoxic ischemic injury or inflammatory injury are the main causes of cerebral palsy. Previous studies including our works confirmed that melatonin has a protective effect against convulsive brain damage during development and that it affects the expression of various molecules involved in processes such as metabolism, plasticity and signaling in the brain. Integral membrane protein plppr5 is a new member of the plasticity-related protein family, which is specifically expressed in brain and spinal cord, and induces filopodia formation as well as neurite growth. It is highly expressed in the brain, especially in areas of high plasticity, such as the hippocampus. The signals are slightly lower in the cortex, the cerebellum, and in striatum. Noteworthy, during development plppr5 mRNA is expressed in the spinal cord, i.e., in neuron rich regions such as in medial motor nuclei, suggesting that plppr5 plays an important role in the regulation of neurons. However, the existing literature only states that plppr5 is involved in the occurrence and stability of dendritic spines, and research on its possible involvement in neonatal ischemic hypoxic encephalopathy has not been previously reported. We used plppr5 knockout (plppr5−/−) mice and their wild-type littermates to establish a model of hypoxicischemic brain injury (HI) to further explore the effects of melatonin on brain injury and the role of plppr5 in this treatment in an HI model, which mainly focuses on cognition, exercise, learning, and memory. All the tests were performed at 3–4 weeks after HI. As for melatonin treatment, which was performed 5 min after HI injury and followed by every 24h. In these experiments, we found that there was a significant interaction between genotype and treatment in novel object recognition tests, surface righting reflex tests and forelimb suspension reflex tests, which represent learning and memory, motor function and coordination, and the forelimb grip of the mice, respectively. However, a significant main effect of genotype and treatment on performance in all behavioral tests were observed. Specifically, wild-type mice with HI injury performed better than plppr5−/− mice, regardless of treatment with melatonin or vehicle. Moreover, treatment with melatonin could improve behavior in the tests for wild-type mice with HI injury, but not for plppr5−/− mice. This study showed that plppr5 knockout aggravated HI damage and partially weakened the neuroprotection of melatonin in some aspects (such as novel object recognition test and partial nerve reflexes), which deserves further study.

As a new network architecture, information-centric networking (ICN) decouples the identifiers and locators of network entities and makes full use of in-network cache technology to improve the content distribution efficiency. For reliable multicast, ICN in-network cache can help reduce the loss recovery delay. However, with the development of applications and services, a multicast tree node often serves multiple reliable multicast groups. How to reasonably allocate cache resources for each multicast group will greatly affect the performance of reliable multicast. In order to improve the overall loss recovery performance of reliable multicast, this paper designs a dynamic cache allocation mechanism (DCAM). DCAM considers the packet loss probability, the node depth of the multicast tree, and the multicast transmission rate of multicast group, and then allocates cache space for multicast group based on the normalized cache quota weight. We also explore the performance of three cache allocation mechanisms (DCAM, AARM, and Equal) combined with four cache strategies (LCE, CAPC, Prob, and ProbCache), respectively. Experimental results show that DCAM can adjust cache allocation results in time according to network changes, and its combinations with various cache strategies outperform other combinations. Moreover, the combination of DCAM and CAPC can achieve optimal performance in loss recovery delay, cache hit ratio, transmission completion time, and overhead.

Background: Collagen type XI α1 (COL11A1) is associated with tumorigenesis and development in many human malignancies. Previous reports indicate that COL11A1 may be a significant diagnostic marker for pancreatic ductal adenocarcinoma (PDAC); however, its biological role in PDAC progression remains unclear. In this study, we investigated the influence of COL11A1 on the invasion and migration abilities of pancreatic cancer cells and explored its potential molecular mechanisms. Methods: Cell migration and invasion were assessed using Transwell assays in pancreatic cancer cells transfected with siCOL11A1 and pCNV3-COL11A1 plasmids. The protein and mRNA expression levels of N-cadherin, E-cadherin, Vimentin, cluster of differentiation (CD)-24, CD44, serine–threonine kinase (AKT), glycogen synthase kinase (GSK)-3β, phospho (p)-AKTSer473, p-GSK-3βSer9, and Snail were analyzed using Western blotting and real-time polymerase chain reaction (PCR). The effect of COL11A1 on cell stemness was tested using flow cytometry and clone formation assays. Results: These results demonstrated that COL11A1 significantly promoted the invasion and migration abilities of PDAC cells. Furthermore, COL11A1 facilitated the occurrence of epithelial–mesenchymal transition (EMT) and cell stemness by upregulating the expression levels of p-AKTSer473, p-GSK-3βSer9, and Snail. Conclusions: This study suggests that the activation of the AKT/GSK-3β/Snail signaling pathway induced by COL11A1 plays a major role in the progression of PDAC. Therefore, COL11A1 could serve as a potential target for PDAC treatment.

Information-centric networking (ICN) is expected to be a candidate for future internet architecture, and it supports features such as multicast that improves bandwidth utilization and transmission efficiency. However, multicast itself does not provide congestion control. When multiple multicast groups coexist, multicast traffic may exhaust all network resources, and cause network congestion and packet loss. Additionally, traditional IP multicast congestion control mechanisms cannot be directly applied to ICN architecture. Therefore, it is necessary to consider an effective congestion control mechanism for ICN multicast. This paper proposes a single-rate multicast congestion control mechanism, called SRMCC. It supports router-assisted awareness of the network congestion state and congestion control message aggregation. Moreover, the fair shared rate estimation method is innovatively proposed to achieve protocol fairness. Most importantly, it adjusts the rate according to different congestion states indicated by the queue occupancy ratio. By introducing a rate selection factor, it can achieve a balance between packet loss rate and throughput. Experimental results show that our proposal outperforms other mechanisms in throughput, packet loss rate, total bandwidth utilization, and overhead, and achieves protocol fairness and better TCP friendliness.

Adipokines, including leptin, visfatin, adiponectin, and interleukin-6 (IL)-6, play multiple roles in the pathophysiology of epilepsy and febrile seizures (FS). We aimed to investigate the associations among plasma adipokines, mainly leptin, visfatin, adiponectin, or IL-6, and the prognosis of FS. This prospective cross-sectional study was conducted from January 2017 to December 2018 at the Wuxi Second People' Hospital China. The levels of serum leptin, visfatin, adiponectin, and IL-6 in 55 children with FS (FS group) were compared with 42 febrile children without seizure (FC group) and 48 healthy children (HC group) in an acute phase. The correlation with clinical indicators was determined by logistic regression analysis. Serum adiponectin and IL-6 levels were significantly higher in the FS group than in the FC and HC groups (p < 0.05), but there was no statistical difference between the FC and HC groups. In addition, logistic regression analysis showed that high concentrations of adiponectin and IL-6 were significantly associated with the occurrence of FS. For leptin and visfatin, they were significantly lower in the FS and FC groups than in the normal control group, but there was no statistical difference between the FS and FC groups. Our results suggest that higher plasma levels of IL-6 and adiponectin may serve as an additional biomarker in the early treatment or follow-up of the FS children.

The ketogenic diet (KD) demonstrates antiepileptogenic and neuroprotective efficacy, but the precise mechanisms are unclear. Here we explored the mechanism through systematic proteomics analysis of the lithium chloride-pilocarpine rat model. Sprague-Dawley rats (postnatal day 21, P21) were randomly divided into control (Ctr), seizure (SE), and KD treatment after seizure (SE + KD) groups. Tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectroscopy (LC-MS/MS) were utilized to assess changes in protein abundance in the hippocampus. A total of 5,564 proteins were identified, of which 110 showed a significant change in abundance between the SE and Ctr groups (18 upregulated and 92 downregulated), 278 between SE + KD and SE groups (218 upregulated and 60 downregulated), and 180 between Ctr and SE + KD groups (121 upregulated and 59 downregulated) (all p < 0.05). Seventy-nine proteins showing a significant change in abundance between SE and Ctr groups were reciprocally regulated in the SD + KD group compared to the SE group (i.e., the seizure-induced change was reversed by KD). Of these, five (dystrobrevin, centromere protein V, oxysterol-binding protein, tetraspanin-2, and progesterone receptor membrane component 2) were verified by parallel reaction monitoring. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that proteins of the synaptic vesicle cycle pathway were enriched both among proteins differing in abundance between SE and Ctr groups as well as between SE + KD and SE groups. This comprehensive proteomics analyze of KD-treated epilepsy by quantitative proteomics revealed novel molecular mechanisms of KD antiepileptogenic efficacy and potential treatment targets.

The segmentation of brain region contours in three dimensions is critical for the analysis of different brain structures, and advanced approaches are emerging continuously within the field of neurosciences. With the development of high-resolution micro-optical imaging, whole-brain images can be acquired at the cellular level. However, brain regions in microscopic images are aggregated by discrete neurons with blurry boundaries, the complex and variable features of brain regions make it challenging to accurately segment brain regions. Manual segmentation is a reliable method, but is unrealistic to apply on a large scale. Here, we propose an automated brain region segmentation framework, DeepBrainSeg, which is inspired by the principle of manual segmentation. DeepBrainSeg incorporates three feature levels to learn local and contextual features in different receptive fields through a dual-pathway convolutional neural network (CNN), and to provide global features of localization by image registration and domain-condition constraints. Validated on biological datasets, DeepBrainSeg can not only effectively segment brain-wide regions with high accuracy (Dice ratio > 0.9), but can also be applied to various types of datasets and to datasets with noises. It has the potential to automatically locate information in the brain space on the large scale.

The grasshopper optimization algorithm (GOA) is a novel metaheuristic algorithm. Because of its easy deployment and high accuracy, it is widely used in a variety of industrial scenarios and obtains good solution. But, at the same time, the GOA algorithm has some shortcomings: (1) original linear convergence parameter causes the processes of exploration and exploitation unbalanced; (2) unstable convergence speed; and (3) easy to fall into the local optimum. In this paper, we propose an enhanced grasshopper optimization algorithm (EGOA) using a nonlinear convergence parameter, niche mechanism, and the β-hill climbing technique to overcome the abovementioned shortcomings. In order to evaluate EGOA, we first select the benchmark set of GOA authors to test the performance improvement of EGOA compared to the basic GOA. The analysis includes exploration ability, exploitation ability, and convergence speed. Second, we select the novel CEC2019 benchmark set to test the optimization ability of EGOA in complex problems. According to the analysis of the results of the algorithms in two benchmark sets, it can be found that EGOA performs better than the other five metaheuristic algorithms. In order to further evaluate EGOA, we also apply EGOA to the engineering problem, such as the bin packing problem. We test EGOA and five other metaheuristic algorithms in SchWae2 instance. After analyzing the test results by the Friedman test, we can find that the performance of EGOA is better than other algorithms in bin packing problems.

Background. Acupuncture has been used to treat amnestic mild cognitive impairment (aMCI) for many years in China. However, the long-term effects of continuous acupuncture treatment remained unclear. Objective. We aimed to explore the long-term effects of continuous acupuncture treatment on hippocampal functional connectivity (FC) in aMCI. Methods. Fifty healthy control (HC) participants and 28 aMCI patients were recruited for resting-state functional magnetic resonance imaging (fMRI) at baseline. The 28 aMCI patients were then divided into the aMCI acupuncture group, which received acupuncture treatment for 6 months, and the aMCI control group, which received no intervention. All aMCI patients completed the second resting-state fMRI scanning after 6 months of acupuncture treatment. Analysis based on the region of interest and two-way analysis of covariance were both used to explore the long-term effects of acupuncture on cognition change and hippocampal FC in aMCI. Results. Compared to HC, aMCI showed decreased right hippocampal FC with the right inferior/middle temporal gyrus (ITG/MTG), left amygdala, and the right fusiform and increased FC with bilateral caudates at baseline. After acupuncture treatment, the right hippocampal FC with right ITG/MTG enhanced significantly in the aMCI acupuncture group, but continued to decrease in the aMCI control group. Whole brain FC analysis showed enhanced right hippocampal FC with the right ITG and the left MTG in the aMCI acupuncture group relative to the aMCI control group. Furthermore, FC strength of the right hippocampus with right ITG at baseline was negatively correlated with the changes in memory scores of aMCI acupuncture patients. Conclusion. Acupuncture treatment could alleviate the progression of cognitive decline and could enhance hippocampal FC with ITG and MTG in aMCI that may be associated with resilience to resistant against neurodegeneration. The findings provided a better understanding of the long-term effects of acupuncture treatment and confirmed the therapeutic role of acupuncture in aMCI.

As an emerging network architecture, Information-Centric Networking (ICN) is considered to have the potential to meet the new requirements of the Fifth Generation (5G) networks. ICN uses a name decoupled from location to identify content, supports the in-network caching technology, and adopts a receiver-driven model for data transmission. Existing ICN congestion control mechanisms usually first select a nearby replica by opportunistic cache-hits and then insist on adjusting the transmission rate regardless of the congestion state, which cannot fully utilize the characteristics of ICN to improve the performance of data transmission. To solve this problem, this paper proposes a two-level congestion control mechanism, called 2LCCM. It switches the replica location based on a node state table to avoid congestion paths when heavy congestion happens. This 2LCCM mechanism also uses a receiver-driven congestion control algorithm to adjust the request sending rate, in order to avoid link congestion under light congestion. In this paper, the design and implementation of the proposed mechanism are described in detail, and the experimental results show that 2LCCM can effectively reduce the transmission delay when heavy congestion occurs, and the bandwidth-delay product-based congestion control algorithm has better transmission performance compared with a loss-based algorithm.

Software-Defined Network (SDN), which is recommended as a new generation of the network, a substitute for TCP/IP network, has the characteristics of separation of data plane and control plane. Although the separation of the control plane brings a high degree of freedom and simple operation and maintenance, it also increases the cost of north–south communication. There are many additional modules for SDN to modify and enhance the basic functions of SDN. This paper proposes a message queue-based northbound communication mechanism, which pre-categorizes messages from the data plane and accurately pushes them to the apps potentially interested. This mechanism improves the efficiency of northbound communication and apps’ execution. Furthermore, it supports both OpenFlow and the protocol-independent southbound interface, and it has strong compatibility. Experiments have proved that this mechanism can reduce the control-response latency by up to 41% when compared with the normal controller northbound communication system, and it also improves the network situation of the data plane, such as real-time bandwidth.

Limited by the tiny structure of axons, the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated. Here, we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons. We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity. Furthermore, inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals. Concurrent with somatic depolarization, inhibitory inputs on axons decrease neuronal excitability and impede spike generation. In addition, following action potentials, inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision. These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity (suppression or facilitation) according to neuronal network patterns.

Background: China began to implement the national medical and health system and public hospital reforms in 2009 and 2012, respectively. Anhui Province is one of the four pilot provinces, and the medical reform measures received wide attention nationwide. The effectiveness of the above reform needs to get attention. This study aimed to master the efficiency and productivity of county-level public hospitals based on the data envelopment analysis (DEA) model and Malmquist index in Anhui, China, and then provide improvement measures for the future hospital development. Methods: We chose 12 country-level hospitals based on geographical distribution and the economic development level in Anhui Province. Relevant data that were collected in the field and then sorted were provided by the administrative departments of the hospitals. DEA models were used to calculate the dynamic efficiency and Malmquist index factors for the 12 institutions. Results: During 2010–2015, the overall average relative service efficiency of 12 county-level public hospitals was 0.926, and the number of hospitals achieved an effective DEA for each year from 2010 to 2015 was 4, 6, 7, 7, 6, and 8, respectively, as measured using DEA. During this same period, the average overall production efficiency was 0.983, and the total productivity factor had declined. The overall production efficiency of five hospitals was >1, and the rest are

We previously illustrated that long-term upregulated expression of ZnT-3 in the hippocampus of rats that underwent neonatal seizures was restored by pretreatment with a ketogenic diet. It was recently demonstrated that upregulated expression of ZnT-3 was associated with increased concentrations of intracellular free zinc ions in an in vitro model of glutamate-induced hippocampal neuronal excitotoxic damage. However, there is still a lack of research on the effects of different concentrations of zinc in the diet on developmental convulsive brain injury. The aim of this study was to investigate the effects of different zinc concentrations in the diet on long-term neurobehavioral and seizure thresholds following lithium chloride-pilocarpine-induced developmental seizures. Sprague-Dawley rats (postnatal day 27, P27) were randomly assigned to one of six dietary groups for 4 weeks: normal zinc control group (Control group, 44 mg/kg Zn), Zn-deficient control group (ZD group, 2.7 mg/kg Zn), Zn supplemented control group (ZS group, 246 mg/kg Zn), pilocarpine-induced seizure plus regular zinc diet group (SE group, 44 mg/kg Zn), seizure plus low-zinc diet group (SE + ZD group, 2.7 mg/kg Zn), and seizure plus high-zinc diet group (SE + ZS group, 246 mg/kg Zn). Novel object recognition and passive avoidance tests were performed on rats at P42 and P56. After routine seizure threshold detection and Timm staining procedures at P57, expression of GPR39, ZnT-3, and MBP were detected in the hippocampus by Western blot analysis. The results revealed that the Zinc-deficient diet for 4 weeks aggravated the long-term adverse effects of developmental seizures, evidenced by weight, cognition, seizure threshold and serum zinc concentrations, which were paralleled by expression changes in hippocampal GPR39 and ZnT-3. In contrast, zinc supplementation for 4 weeks significantly improved damage-related changes described above and rescued the abnormal expression of GPR39, ZnT-3, and MBP in the hippocampus. Similar alterations between the expression pattern of MBP and aberrant sprouting of mossy fibers in the hippocampus may indicate that sprouting is a secondary pathological change caused by developmental brain damage rather than the cause of epileptogenesis. Up-regulation of MBP protein levels in the high zinc diet-treated seizure group as well as the corresponding improvement of cognitive impairment and reduced hippocampal mossy fiber regenerative sprouting, may represent a compensatory mechanism for neuronal membrane damage and repair.

Recent evidence indicates that autophagy-mediated mitochondrial homeostasis is crucial for oxidative stress-related brain damage and repair. The highest concentration of melatonin is in the mitochondria of cells, and melatonin exhibits well-known antioxidant properties. We investigated the impact and mechanism involved in mitochondrial function and the mitochondrial oxidative stress/autophagy regulator parameters of glutamate cytotoxicity in mouse HT22 hippocampal neurons. We tested the hypothesis that melatonin confers neuroprotective effects via protecting against mitochondrial impairment and mitophagy. Cells were divided into four groups: the control group, melatonin alone group, glutamate injury group, and melatonin pretreatment group. We found that glutamate induced significant changes in mitochondrial function/oxidative stress-related parameters. Leptin administration preserved mitochondrial function, and this effect was associated with increased superoxide dismutase, glutathione (GSH), and mitochondrial membrane potential and decreased GSSG (oxidized glutathione) and mitochondrial reactive oxygen species. Melatonin significantly reduced the fluorescence intensity of mitophagy via the Beclin-1/Bcl-2 pathway, which involves Beclin-1 and Bcl-2 proteins. The mitophagy inhibitor CsA corrected these glutamate-induce changes, as measured by the fluorescence intensity of Mitophagy-Tracker Red CMXROS, mitochondrial ROS, and mitochondrial membrane potential changes. These findings indicate that melatonin exerts neuroprotective effects against glutamate-induced excitotoxicity by reducing mitophagy-related oxidative stress and maintaining mitochondrial function.

While a ketogenic diet (KD) is a well-established therapy for medically intractable epilepsy, clinical evidence of relevant adverse events of a KD has also been reported. We asked whether this kind of diet would have deleterious effects on wild-type brain function by evaluating KD-induced biochemical changes in the hippocampus as well as neurobehavioral changes occurring in wild-type rats. Fifty-four Sprague-Dawley rats were randomly assigned to three groups on postnatal day 28 (P28): wild-type rats fed with a KD qd (daily for 4 weeks, KD) or qod (every other day for 4 weeks, KOD), and wild-type rats fed with standard normal laboratory diet (ND). Neurobehavioral changes were observed on P35, P42, and P49. The hippocampal mossy fiber sprouting, the expression levels of zinc transporters (ZnTs) and lipid metabolism related genes were detected by Timm staining, RT-qPCR and western blot analysis, respectively, on P58. The KD-treated KOD and KD groups showed a significant delay of negative geotaxis reflex on P35, but not on P42 or P49. In the open field test, daily KD treatment only led to a reduction in exploratory activity and increased grooming times but induced no significant changes in the scores of vertical activity or delay time. KD qod treated rats (KOD) displayed a slight delay in the place navigation test on P35 compared with the KD group. There were no significant differences in Timm staining among the three groups. In parallel with these changes, KD treatment (both KD and KOD) induced significantly downregulated mRNA levels of Apoa1, Pdk4, and upregulated expression of ApoE, ANXN7, and cPLA2 in the hippocampus when compared with the ND group (except in the case of ApoE in the KOD group). Notably, both the mRNA and protein levels of cPLA2 in the KOD rats were significantly downregulated compared with the KD group but still markedly higher than in the ND group. No significant difference was found in ZnTs among the three groups. Our data suggest that early-life KD can provoke minor neurobehavioral effects in particular a delay in negative geotaxis reflex and an increase in grooming activity. The hippocampal lipid metabolism signaling pathway, especially cPLA2, may be the target of the protective effect of KD on long-term brain injury after developmental seizures.

Background: The cornu ammonis (CA), as part of the hippocampal formation, represents a primary target region of neural degeneration in amnestic mild cognitive impairment (aMCI). Previous studies have revealed subtle structural deficits of the CA subregions (CA1-CA3, bilateral) in aMCI; however, it is not clear how the network function is impacted by aMCI. The present study examined longitudinal changes in resting state functional connectivity (FC) of each CA subregion and how these changes relate to neuropsychological profiles in aMCI.Methods: Twenty aMCI and 20 healthy control (HC) participants underwent longitudinal cognitive assessment and resting state functional MRI scans at baseline and 15 months afterward. Imaging data were processed with published routines in SPM8 and CONN software. Two-way analysis of covariance was performed with covariates of age, gender, education level, follow up interval, gray matter volume, mean FD, as well as global correlation (GCOR). Pearson’s correlation was conducted to evaluate the relationship between the longitudinal changes in CA subregional FC and neuropsychological performance in aMCI subjects.Results: Resting state FC between the right CA1 and right middle temporal gyrus (MTG) as well as between the left CA2 and bilateral cuneal cortex (CC) were decreased in aMCI subjects as compared to HC. Longitudinal decrease in FC between the right CA1 and right MTG was correlated with reduced capacity of episodic memory in aMCI subjects.Conclusion: The current findings suggest functional alterations in the CA subregions. CA1 connectivity with the middle temporal cortex may represent an important neural marker of memory dysfunction in aMCI.

The major advantage of information-centric networking (ICN) lies in in-network caching. Ubiquitous cache nodes reduce the user’s download latency of content and the drain of network bandwidth, which enables efficient content distribution. Due to the huge cost of updating an entire network infrastructure, it is realistic for ICN to be integrated into an IP network, which poses new challenges to design a cache system and corresponding content router. In this paper, we firstly observed that the behavior pattern of data requests based on a name resolution system (NRS) makes an ICN cache system implicitly form a hierarchical and nested structure. We propose a complete design and an analytical model to characterize an uncooperative hierarchical ICN caching system compatible with IP. Secondly, to facilitate the incremental deployment of an ICN cache system in an IP network, we designed and implemented a cache-supported router with multi-terabyte cache capabilities. Finally, the simulation and measurement results show the accuracy of proposed analytical model, the significant gains on hit ratio, and the access latency of the hierarchical ICN cache system compared with a flat cache system based on naming routing, as well as the high performance of the implemented ICN router.

The role of leptin in the pathogenesis of epilepsy is getting more and more attention in clinical and basic research. Although there are data indicating neuroprotective effects of elevated serum/brain leptin levels following acute seizures, no study to date has dealt with the impact of chronic leptin treatment on long-term brain injury following developmental seizures. The aim of this study was to evaluate whether chronic leptin treatment may have neuroprotective effects on cognitive and hippocampal mossy fiber sprouting following flurothyl-induced recurrent neonatal seizures and whether these effects are mediated by the zinc/CaMKII-associated mitophagy signaling pathway. Forty Sprague-Dawley rats (postnatal day 6, P6) were randomly assigned into two groups: neonatal seizure group and control group. At P13, they were further divided into control group, seizure group (RS), control + leptin (leptin, i.p., 2 mg/kg/day for 10 days), seizure+leptin group (RS+Leptin, 2mg/kg/day, i.p., for 10 consecutive days). Morris water maze test was performed during P27-P32. Subsequently, Timm staining and Western blotting were used to detect the mossy fiber sprouting and protein levels in hippocampus. Flurothyl-induced seizures (RS group) significantly down-regulated mitophagy markers PINK, Drp1, PHB, and memory marker CaMK II alpha while up-regulating zinc transporters ZnT3, ZnT4, ZIP7, and autophagy execution molecular cathepsin-E, which were paralleled with hippocampal aberrant mossy fiber sprouting and cognitive dysfunction. However, these changes were restored by chronic leptin treatment (RS+Leptin group). The results showed that leptin had neuroprotective effect on hippocampal pathological damage and cognitive deficits induced by neonatal seizures and suggested that Zinc/CaMK II associated-mitophagy signaling pathway in hippocampus may be a new target of leptin's neuroprotection, with potential value of translational medicine.

Developmental seizure-induced long-term neuronal hyperexcitation is partially mediated by regenerative mossy fiber sprouting in hippocampus. Yet, there are no effective drugs available to block this pathological process. Recently, leptin has been shown to prevent the sprouting of hippocampal mossy fibers and abnormalities in the neurobehavioral parameters. However, their underlying molecular mechanisms are largely unknown. The purpose of this study was to determine the effect of glutamate on the parameters of zinc homeostasis, mitochondrial functions, and mitophagy regulating factors, as well as to investigate the protective effects of leptin against cytotoxicity of glutamate in murine HT22 hippocampal neuronal cells. Cells were assigned to one of the four groups as follows: control group, leptin alone group, glutamate injury group, and leptin pretreatment group. Our results demonstrated that glutamate induced a decrease in superoxide dismutase, GSH (glutathione), and mitochondrial membrane potential and an increase in GSSG (oxidized glutathione), mitochondrial reactive oxygen species, and supplementation of leptin blocked the toxic effect of glutamate on cell survival. The glutamate-induced cytotoxicity was associated with an increase in mitophagy and intracellular zinc ion levels. Furthermore, glutamate activated the mitophagy markers PINK1, Parkin, and the ratio of LC3-II/LC3-I, as well as increased the expression of zinc transporter 3 (ZnT3). Leptin corrected these glutamate-caused alterations. Finally, the mitophagy inhibitor, CsA, significantly reduced intracellular zinc ion content and ZnT3 expression. These results suggest that mitophagy-mediated zinc dyshomeostasis and mitochondrial activation contributed to glutamate-induced HT22 neuronal cell injury and that leptin treatment could counteract these detrimental effects, thus highlighting mitophagy-mediated zinc homeostasis via mitochondrial activation as a potential strategy to counteract neuroexcitotoxicity.