Method for analyzing urban waterlogging mechanisms based on a 1D-2D water environment dynamic bidirectional coupling model.

Urban waterlogging is a significant global issue. To achieve precisely control urban waterlogging and enhance our understanding of its causes, a novel study method was introduced. This method is based on a dynamic bidirectional coupling model that combines 1D-2D hydrodynamic and water quality simulations. The waterlogging phenomenon in densely populated metropolitan areas of Changzhi city, China, was studied. This study focused on investigating the process involved in waterlogging formation, particularly overflow at nodes induced by the design of the topological structure of the pipe network, constraints on the capacity of the underground drainage system, and the surface runoff accumulation. The complex interplay among these elements and their possible influences on waterlogging formation were clarified. The results indicated notable spatial and temporal variation in the waterlogging formation process in densely populated urban areas. Node overflow in the drainage system emerged as the key influencing factor in the waterlogging formation process, accounting for up to 71% of the total water accumulation at the peak time. The peak lag time of waterlogging during events with short return periods was primarily determined by the rainfall peak moment. In contrast, the peak time of waterlogging during events with long return periods was influenced by the rainfall peak moment, drainage capacity and topological structure of the pipe network. Notably, the access of inflow from both upstream and downstream segments of the pipe network drainage system significantly impacted the peak time of waterlogging, with upstream water potentially delaying the peak time substantially. This study not only provides new insights into urban waterlogging mechanisms but also provides practical guidance for optimizing urban drainage systems, urban planning, and disaster risk management.

Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption.

Background: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury. Methods: First, LCD nanoparticles, engineered with covalent conjugation between luminol and ß-cyclodextrin (ß-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry. Results: LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ T cells, but the use of LCD nanoparticles suppressed this increase. Conclusions: Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury.

Experimental study of rainwater grate blocking and submergence of outfall on drainage network capacity.

Accurately evaluating the performance of urban underground drainage network and its influencing factors is a challenging problem, as this process is affected by many complex factors. In this study, based on an overland flow experiment considering drainage process of pipe network, a series of physical model experiments were conducted to investigate the influences of different surface slopes, rainwater grate blockage and the submergence of outfall on the performance of the drainage pipe network system. The hydrographs of surface runoff and pipe network flow were recorded in collection tanks by precise digital pressure sensors to provide comprehensive information about the characteristics of drainage performance in the pipe network. Through a series of experimental data collection and analysis, the following conclusions are drawn from this study: (1) The longitudinal slope of the road decreases the pipe drainage capacity by 1.68%-8.94%, and this reduction effect is more significant with the increase of slope. (2) The blockage of rainwater grate at different locations has different impacts on the road drainage system, the downstream rainwater grate blockage has the most obvious impact on the performance of the drainage system, which reduces the drainage capacity by 22.59%-25.38%. (3) Different submergence degrees of rainwater outlet have different impacts on the drainage system. Under different slopes, the drainage capacity of the pipe network decreases by 1.88%-23.46% with the increase of the submergence degree of the outfall. These experimental results are helpful in understanding the working conditions of urban road drainage system and the influencing factors of the system's drainage capacity, and also provide measured data for verification of relevant numerical models and coefficient calibration.

Vagus Nerve Stimulation Prevents Endothelial Necroptosis to Alleviate Blood-Spinal Cord Barrier Disruption After Spinal Cord Injury.

Vagus nerve stimulation (VNS) is a promising neuromodulation technique, which has been demonstrated to promote functional recovery after spinal cord injury (SCI) in our previous study. But the underlying mechanism remains to be explored. Using a compressed SCI model, our present study first demonstrated that activated microglia produce abundant tumor necrosis factor-α (TNF-α) to induce endothelial necroptosis via receptor-interacting protein kinase 1 (RIP1)/RIP3/mixed lineage kinase domain-like protein (MLKL) pathway, thus destroying the blood-spinal cord barrier (BSCB) after SCI. While both TNF-α specifical antibody (infliximab) and necroptosis inhibitor (necrostatin-1) alleviate BSCB disruption. Then our study found that VNS significantly inhibits microglia-derived TNF-α production and reduces expression of p-RIP3 and p-MLKL in endothelial cells. As expected, further results indicated that VNS mitigates the BSCB disruption, thus reducing inflammatory cells infiltration and neural damage. Finally, both electrophysiological evaluation and locomotor test demonstrated that VNS promotes motor function recovery after SCI. In conclusion, our data demonstrated VNS restricts microglia-derived TNF-α to prevent RIP1/RIP3/MLKL mediated endothelial necroptosis, thus alleviating the decisive pathophysiological BSCB disruption to reduce neuroinflammation and neural damage, which ultimately promotes motor function recovery after SCI. Therefore, these results further elaborate that VNS might be a promising therapeutic strategy for SCI. Vagus nerve stimulation prevents microglia-derived TNF-α induced endothelial necroptosis to alleviate blood-spinal cord barrier disruption after spinal cord injury.

The correlation between upper body grip strength and resting-state EEG network.

Current research in the field of neuroscience primarily focuses on the analysis of electroencephalogram (EEG) activities associated with movement within the central nervous system. However, there is a dearth of studies investigating the impact of prolonged individual strength training on the resting state of the brain. Therefore, it is crucial to examine the correlation between upper body grip strength and resting-state EEG networks. In this study, coherence analysis was utilized to construct resting-state EEG networks using the available datasets. A multiple linear regression model was established to examine the correlation between the brain network properties of individuals and their maximum voluntary contraction (MVC) during gripping tasks. The model was used to predict individual MVC. The beta and gamma frequency bands showed significant correlation between RSN connectivity and MVC (p < 0.05), particularly in left hemisphere frontoparietal and fronto-occipital connectivity. RSN properties were consistently correlated with MVC in both bands, with correlation coefficients greater than 0.60 (p < 0.01). Additionally, predicted MVC positively correlated with actual MVC, with a coefficient of 0.70 and root mean square error of 5.67 (p < 0.01). The results show that the resting-state EEG network is closely related to upper body grip strength, which can indirectly reflect an individual's muscle strength through the resting brain network.

Effects of cerebellar transcranial direct current stimulation on rehabilitation of upper limb motor function after stroke.

Background: The cerebellum is involved in the control and coordination of movements but it remains unclear whether stimulation of the cerebellum could improve the recovery of upper limb motor function. Therefore, this study aimed to explore whether cerebellar transcranial direct current stimulation (tDCS) therapy could promote the recovery of upper limb motor function in patients who suffered a stroke. Methods: In this randomized, double-blind, and sham-controlled prospective study, 77 stroke patients were recruited and randomly assigned to the tDCS group (n = 39) or the control group (n = 38). The patients received anodal (2 mA, 20 min) or sham tDCS therapy for 4 weeks. The primary outcome was the change in the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score from baseline to the first day after 4 weeks of treatment (T1) and 60 days after 4 weeks of treatment (T2). The secondary outcomes were the FMA-UE response rates assessed at T1 and T2. Adverse events (AEs) related to the tDCS treatment were also recorded. Results: At T1, the mean FMA-UE score increased by 10.7 points [standard error of the mean (SEM) = 1.4] in the tDCS group and by 5.8 points (SEM = 1.3) in the control group (difference between the two groups was 4.9 points, P = 0.013). At T2, the mean FMA-UE score increased by 18.9 points (SEM = 2.1) in the tDCS group and by 12.7 points (SEM = 2.1) in the control group (the difference between the two groups was 6.2 points, P = 0.043). At T1, 26 (70.3%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared to 12 (34.3%) patients in the control group (the difference between the two groups was 36.0%, P =0.002). At T2, 33 (89.2%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared with 19 (54.3%) patients in the control group (the difference between the two groups was 34.9%, P = 0.001). There was no statistically significant difference in the incidence of adverse events between the two groups. In the subgroup analysis of different hemiplegic sides, the rehabilitation effect of patients with right hemiplegia was better than that of patients with left hemiplegia (P < 0.05); in the age subgroup analysis, different age groups of patients did not show a significant difference in the rehabilitation effect (P > 0.05). Conclusion: Cerebellar tDCS can be used as an effective and safe treatment to promote recovery of upper limb motor function in stroke patients. Trial registration: ChiCTR.org.cn, identifier: ChiCTR2200061838.

Transcranial direct current stimulation regulates phenotypic transformation of microglia to relieve neuropathic pain induced by spinal cord injury.

Objective: Neuropathic pain is a common complication after spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) has been confirmed to be effective in relieving neuropathic pain in patients with SCI. The aim of this study is to investigate the effect of tDCS on neuropathic pain induced by SCI and its underlying mechanism. Materials and methods: The SCI model was induced by a clip-compression injury and tDCS stimulation was performed for two courses (5 days/each). The motor function was evaluated by Basso-Beattie-Bresnahan (BBB) score, and the thermal withdrawal threshold was evaluated by the thermal radiation method. The effects of tDCS on the cerebral cortex, thalamus, midbrain, and medulla were detected by the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Results: The results showed that SCI reduced the thermal withdrawal threshold and increased the concentration of inflammatory cytokines in the cortex, thalamus, midbrain, and medulla, including the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). In addition, the activation of microglia and the proportion of M1 phenotypic polarization increased significantly in the ventral posterolateral (VPL), ventral tegmental (VTA), and periaqueductal gray (PAG) regions after SCI. After tDCS treatment, the thermal withdrawal threshold and motor function of SCI rats were significantly improved compared to the vehicle group. Meanwhile, tDCS effectively reduced the concentration of pro-inflammatory cytokines in the cortex, thalamus, midbrain, and medulla and increased the concentration of anti-inflammatory cytokines interleukin-10 (IL-10) in the thalamus. In addition, tDCS reduced the proportion of the M1 phenotype of microglia in VPL, VTA, and PAG regions and increase the proportion of the M2 phenotype. Conclusion: The results suggest that tDCS can effectively relieve SCI-induced neuropathic pain. Its mechanism may be related to regulating the inflammatory and anti-inflammatory cytokines in corresponding brain regions via promoting the phenotypic transformation of microglia.

Depression mediated the relationships between precentral-subcortical causal links and motor recovery in spinal cord injury patients.

Depression after brain damage may impede the motivation and consequently influence the motor recovery after spinal cord injury (SCI); however, the neural mechanism underlying the psychological effects remains unclear. This study aimed to examine the casual connectivity changes of the emotion-motivation-motor circuit and the potential mediating effects of depression on motor recovery after SCI. Using the resting-state functional magnetic resonance imaging data of 35 SCI patients (24 good recoverers, GR and 11 poor recoverers, PR) and 32 healthy controls (HC), the results from the conditional Granger causality (GC) analysis demonstrated that the GR group exhibited sparser emotion-motivation-motor GC network compared with the HC and PR groups, though the in-/out-degrees of the emotion subnetwork and the motor subnetwork were relatively balanced in the HC and GR group. The PR group showed significantly inhibitory causal links from amygdala to supplementary motor area and from precentral gyrus to nucleus accumbens compared with GR group. Further mediation analysis revealed the indirect effect of the 2 causal connections on motor function recovery via depression severity. Our findings provide further evidence of abnormal causal connectivity in emotion-motivation-motor circuit in SCI patients and highlight the importance of emotion intervention for motor function recovery after SCI.

Modelling urban flooding integrated with flow and sediment transport in drainage networks.

Drainage networks play an essential role in mitigating urban flooding, which, nevertheless, are prone to suffer sediment deposits. To date, however, the effects of sediments in drainage networks on urban flooding remain poorly understood. Here an integrated model is proposed for urban flooding. It is composed of a hydrological module for surface runoff integrated with a one-dimensional hydro-sediment-morphodynamic module for coupled open-channel or pressurized flow and sediment transport in drainage networks. The governing equations are solved synchronously using a well-balanced finite volume method. The model is tested against two laboratory cases involving mixed flow and sediment transport in pipes, and the results agree well with observed data. A new residential area with virtually pervious surface and an established urban area with essentially impervious surfaces are studied using the present model to unravel how sediments in drainage networks affect urban flooding under different extreme rainfall and sediment scenarios. The results reveal that sediments alter the discharge hydrographs in the drainage networks to distinct extents under different storm return periods. As far as the present computational cases are concerned, when a third of the pipe diameter is occupied by sediment deposits, the peak pipeline flow discharge decreases by up to 25 %. Accordingly, the surface inundation depth increases by up to 18 %, and the inundation area expands by up to 12 %, characterizing a considerably higher flooding risk. The present findings provide insight into the influences of sediment transport in drainage networks on urban flooding.

Dynamic corticomuscular multi-regional modulations during finger movement revealed by time-varying network analysis.

Objective.A body movement involves the complicated information exchange between the central and peripheral systems, which is characterized by the dynamical coupling patterns between the multiple brain areas and multiple muscle units. How the central and peripheral nerves coordinate multiple internal brain regions and muscle groups is very important when accomplishing the action.Approach.In this study, we extend the adaptive directed transfer function to construct the time-varying networks between multiple corticomuscular regions, and divided the movement duration into different stages by the time-varying corticomuscular network patterns.Main results.The inter dynamical corticomuscular network demonstrated the different interaction patterns between the central and peripheral systems during the different hand movement stages. The muscles transmit bottom-up movement information in the preparation stage, but the brain issues top-down control commands and dominates in the execution stage, and finally the brain's dominant advantage gradually weakens in the relaxation stage. When classifying the different movement stages based on time-varying corticomuscular network indicators, an average accuracy above 74% could be reliably achieved.Significance.The findings of this study help deepen our knowledge of central-peripheral nerve pathways and coordination mechanisms, and also provide opportunities for monitoring and regulating movement disorders.

Vagus Nerve Stimulation Reduces Neuroinflammation Through Microglia Polarization Regulation to Improve Functional Recovery After Spinal Cord Injury.

Background: Spinal cord injury (SCI) is a devastating disease that lacks effective treatment. Interestingly, recent studies indicated that vagus nerve stimulation (VNS), neuromodulation that is widely used in a variety of central nervous system (CNS) diseases, improved motor function recovery after SCI. But the exact underlying mechanism of how VNS ameliorates SCI is unclear. This study aimed to confirm the efficacy and further explore the potential therapeutic mechanism of VNS in SCI. Method: A T10 spinal cord compression model was established in adult female Sprague-Dawley rats. Then the stimulation electrode was placed in the left cervical vagus nerve (forming Sham-VNS, VNS, and VNS-MLA groups). Basso-Beattie-Bresnahan (BBB) behavioral scores and Motor evoked potentials (MEPs) analysis were used to detect motor function. A combination of histological and molecular methods was used to clarify the relevant mechanism. Results: Compared with the Sham-VNS group, the VNS group exhibited better functional recovery, reduced scar formation (both glial and fibrotic scars), tissue damage, and dark neurons, but these beneficial effects of VNS were diminished after alpha 7 nicotinic acetylcholine receptor (α7nAchR) blockade. Specifically, VNS inhibited the pro-inflammatory factors TNF-α, IL-1ß, and IL-6 and increased the expression of the anti-inflammatory factors IL-10. Furthermore, we found that VNS promotes the shift of M1-polarized Iba-1+/CD86+ microglia to M2-polarized Iba-1+/CD206+ microglia via upregulating α7nAchR to alleviate neuroinflammation after SCI. Conclusion: Our results demonstrated that VNS promotes microglial M2 polarization through upregulating α7nAChR to reduce neuroinflammation, thus improving motor function recovery after SCI. These findings indicate VNS might be a promising neuromodulation strategy for SCI.

Neutrophil Extracellular Traps Exacerbate Secondary Injury via Promoting Neuroinflammation and Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

As the first inflammatory cell recruited to the site of spinal cord injury (SCI), neutrophils were reported to be detrimental to SCI. However, the precise mechanisms as to how neutrophils exacerbate SCI remain largely obscure. In the present study, we demonstrated that infiltrated neutrophils produce neutrophil extracellular traps (NETs), which subsequently promote neuroinflammation and blood-spinal cord barrier disruption to aggravate spinal cord edema and neuronal apoptosis following SCI in rats. Both inhibition of NETs formation by peptidylarginine deiminase 4 (PAD4) inhibitor and disruption of NETs by DNase 1 alleviate secondary damage, thus restraining scar formation and promoting functional recovery after SCI. Furthermore, we found that NETs exacerbate SCI partly via elevating transient receptor potential vanilloid type 4 (TRPV4) level in the injured spinal cord. Therefore, our results indicate that NETs might be a promising therapeutic target for SCI.

A dynamic, convenient and accurate method for assessing the flood risk of people and vehicle.

With the increase of extreme rainstorm caused by climate change, and the development of urbanization and the improvement of people's living standard, there is an urgent need to draw a dynamic, convenient and accurate flood risk map for different disaster bearing bodies, so as to protect people's lives and properties, as well as improve people's risk awareness and facilitate people's lives. This study mainly researched a method of drawing a dynamic, convenient and accurate flood risk map for people and vehicle. In this study, the surface runoff is simulated by GPU (Graphics Processing Unit) Accelerated Surface Water Flow and Transport model (GAST model), meanwhile, the flood risk of people and vehicle is graded base on the incipient velocity formulas, the most unfavorable principle and grading method, finally, the method is applied in two application cases. The following results are obtained: (1) this method could assess the flood risk of people and vehicle dynamically, conveniently and accurately; (2) the flood risk of people is less than that of vehicle, for the same flood hazard, time and place; (3) the adverse effect of water depth on flood risk for vehicle is greater than that for people. This method of assessing the flood risk map of people and vehicle is of great significance, for flood risk management, land use plan and emergency management department to reduce flood disaster risk.

Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury.

Motor neuron death is supposed to result in primary motor cortex atrophy after spinal cord injury (SCI), which is relevant to poorer motor recovery for patients with SCI. However, the exact mechanisms of motor neuron death remain elusive. Here, we demonstrated that iron deposition in the motor cortex was significantly increased in both SCI patients and rats, which triggered the accumulation of lipid reactive oxygen species (ROS) and resulted in motor neuronal ferroptosis ultimately. While iron chelator, ROS inhibitor and ferroptosis inhibitor reduced iron overload-induced motor neuron death and promoted motor functional recovery. Further, we found that activated microglia in the motor cortex following SCI secreted abundant nitric oxide (NO), which regulated cellular iron homeostasis-related proteins to induce iron overload in motor neurons. Thus, we conclude that microglial activation induced iron overload in the motor cortex after SCI triggered motor neuronal ferroptosis and impeded motor functional recovery. These findings might provide novel therapeutic strategies for SCI.

Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury.

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials' amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.

Effect of transcranial direct-current stimulation on cognitive function in stroke patients: A systematic review and meta-analysis.

OBJECTIVE: Transcranial direct-current stimulation (tDCS) is a noninvasive approach that can alter brain excitability. Several studies have shown the effectiveness of tDCS in improving language and movement function in stroke patients. However, the effect of tDCS on cognitive function after stroke remains uncertain. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform from inception to April 2, 2019. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of the included studies using the Cochrane Collaboration Risk of Bias Tool. All statistical analyses were performed in RevMan 5.3, and the mean difference (MD) or standard mean difference (SMD) were used as the pooled statistics. RESULTS: Fifteen studies involving 820 participants were included. When compared with passive tDCS, anodal tDCS was associated with improved general cognitive performance as examined by the Minimum Mental State Examination or Montreal Cognitive Assessment (SMD = 1.31, 95% CI 0.91-1.71, P < 0.00001), attention performance (SMD = 0.66, 95% CI 0.11-1.20, P = 0.02). There was no significant difference in memory performance (SMD = 0.41, 95% CI -0.67-1.50, P = 0.46). CONCLUSIONS: tDCS is likely to be effective for patients with cognitive impairment after stroke. The evidence for different effects based on population characteristics and stimulation methods was limited, but a real effect cannot be ruled out. More high-quality research in this field is required to determine the potential benefits of tDCS in the treatment of cognitive deficits after stroke and to establish the optimal treatment program.

Keratinocyte growth factor ameliorates mycophenolate mofetil-induced intestinal barrier disruption in mice.

OBJECTIVES: Although mycophenolate mofetil-induced (MMF) effectively improves long-term graft survival, the gastrointestinal (GI) side effects due to MMF-induced GI barrier damage limit its use in clinic. Keratinocyte growth factor (KGF) plays a crucial role in the intestinal protection and repair process. This study is designed to investigate the protective effect of KGF on MMF-induced intestinal mucosal barrier disruption and the potential mechanism. METHODS: Thirty adult male C57BL/6 mice were assigned to one of the following groups: the MMF group, the MMF + KGF group, and the control group (n = 10 in each group). Animals in the MMF group received MMF (500 mg/kg) by gavage once daily for 15 consecutive days; animals in the MMF + KGF group received MMF (500 mg/kg) by gavage and KGF (5 mg/kg) by intraperitoneal injection once daily for 15 consecutive days; and control mice were given an equal volume of vehicle during the 15-day experimental period. In each group, intestinal paracellular permeability, histopathological changes and shifts in tight junction (TJ) protein were evaluated; further, proliferation and apoptosis of intestinal epithelial cells (IECs) were assessed, and intraepithelial lymphocytes (IELs) were isolated and analyzed by flow cytometry. RESULTS: MMF caused intestinal mucosal injury, increased intestinal mucosal permeability, and altered expression of TJ protein. Moreover, MMF treatment inhibited IEC proliferation and increased apoptosis. MMF treatment resulted in a lower proportion of γδ+ T cells in IELs (γδ+ IELs). Conversely, concurrent administration of KGF with MMF effectively alleviated MMF-induced intestinal mucosal disruption, inhibited the increase in intestinal permeability, and maintained TJ protein expression. KGF also reversed the MMF-mediated inhibition of proliferation and promotion of apoptosis in IECs. In addition, KGF significantly enhanced the proportion of γδ+ IELs. CONCLUSION: Our findings suggest that MMF induces intestinal epithelial barrier disruption in mice. KGF may play a protective role to ameliorate the disruption and provide a therapeutic intervention for gastrointestinal disorders induced by MMF.

Alterations of grey matter volumes and network-level functions in patients with stable chronic obstructive pulmonary disease.

OBJECTIVE: The purpose of this study was to investigate structural and functional alterations of the brain in the patients with stable chronic obstructive pulmonary disorder (COPD) and further investigate how these alterations correlated to parameters of pulmonary function test, cognitive function and disease duration in patients with COPD. METHOD: Forty-five patients with stable COPD and forty age- and gender-matched healthy controls were enrolled into this study. Both resting-state fMRI and structural MRI were acquired for each participant. Voxel-based morphology was utilized to analyze alterations of the grey matter volume (GMV), and the seed-based resting-state functional connectivity (FC) was used to evaluate the network-level functional alterations. RESULTS: Compared to healthy controls, patients with stable COPD showed decreased GMV in the left supramarginal gyrus/precentral gyrus (SMG/PreCG), bilateral posterior midcingulate cortex (pMCC), right middle occipital gyrus (MOG) and right SMG. Furthermore, COPD patients mainly showed decreased FC within the visual network, frontoparietal network and other brain regions. Subsequent correlational analyses revealed that the decreased FC within visual network, frontoparietal network were positively correlated with the Montreal Cognitive Assessment score, language-domain score, attention-domain score and disease duration in patients with COPD. CONCLUSION: Our findings provided evidence that COPD patients showed decreased GMV and regional and network-level functional alterations within the visual network, frontoparietal network and other networks. We speculated that atrophic GMV and FC of visual network and frontoparietal network are involved in the neural mechanism of mild cognitive impairment in stable COPD patients.

Experimental study for effects of terrain features and rainfall intensity on infiltration rate of modelled permeable pavement.

In order to investigate the effects of the terrain slopes and rainfall intensity on the steady infiltration rate of permeable pavement, an experiment with the combinations of three types of permeability, three kinds of rainfall intensity, different cross slope and longitudinal slope are undertaken. Through analyzing the experimental data, it is indicated that: (1) the relation between the steady infiltration rate and the cross and longitudinal slopes can be described by power functions, i.e. as the slopes increase, the steady infiltration rate decreases. The steady infiltration rate can be reduced by 23.3%-72.2% and 12.6%-22.2% for the slopes ranging from 0° to 5° and from 5° to 10°, respectively, illustrating the infiltration is more sensitive to the 0°-5° slope; (2) Under the same conditions, the effect of the cross slope on the steady infiltration rate is about 1.1-1.4 times as high as that of the longitudinal slope, i.e. the cross slope varying could lead to more obvious infiltration change, comparing to the longitudinal slope; (3) The relation between the rainfall intensity and the infiltration rate can be reflected by power function as well. The higher the rainfall intensity, the more the steady infiltration rate increases; (4) The comprehensive effect of the cross slope, longitudinal slope and rainfall intensity on steady infiltration rate can be expressed by quadratic polynomial functions. The main purpose of the manuscript is to determine how the slopes and the rainfall intensities affect the infiltration process and guide the plan and design of the permeable pavement in practical engineering.

Reevaluating the ability of cerebellum in associative motor learning.

It has been well established that the cerebellum and its associated circuitry constitute the essential neuronal system for both delay and trace classical eyeblink conditioning (DEC and TEC). However, whether the cerebellum is sufficient to independently modulate the DEC, and TEC with a shorter trace interval remained controversial. Here, we used direct optogenetic stimulation of mossy fibers in the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS) replacement for the peripheral CS (eg, a tone CS or a light CS) paired with a periorbital shock unconditioned stimulus (US) to examine the ability of the cerebellum to learn the DEC and the TEC with various trace intervals. Moreover, neural inputs to the pontine nucleus (PN) were pharmacological blocked to limit the associative motor learning inside the cerebellum. We show that all rats quickly acquired the DEC, indicating that direct optogenetic stimulation of mossy fibers in the left MCP is a very effective and sufficient CS to establish DEC and to limit the motor learning process inside the cerebellum. However, only five out of seven rats acquired the TEC with a 150-ms trace interval, three out of nine rats acquired the TEC with a 350-ms trace interval, and none of the rats acquired the TEC with a 500-ms trace interval. Moreover, pharmacological blocking glutamatergic and GABAergic inputs to the PN from the extra-cerebellar and cerebellar regions has no significant effect on the DEC and TEC learning with the optogenetic CS. These results indicate that the cerebellum has the ability to independently support both the simple DEC, and the TEC with a trace interval of 150 or 350 ms, but not the TEC with a trace interval of 500 ms. The present results are of great importance in our understanding of the mechanisms and ability of the cerebellum in associative motor learning and memory.