A comparison of ultrasound volume navigation, O-arm navigation, and X-ray guidance for screw placement in minimally invasive transforaminal lumbar interbody fusion: a randomized controlled trial.

OBJECTIVE: To compare the differences between Ultrasound Volume Navigation (UVN), O-arm Navigation, and conventional X-ray fluoroscopy-guided screw placement in Minimally Invasive Transforaminal Lumbar Interbody Fusion (MIS-TLIF) surgeries. METHODS: A total of 90 patients who underwent MIS-TLIF due to lumbar disc herniation from January 2022 to January 2023 were randomly assigned to the UVN group, O-arm group, and X-ray group. UVN, O-arm navigation, and X-ray guidance were used for screw placement in the respective groups, while the remaining surgical procedures followed routine MIS-TLIF protocols. Intraoperative data including average single screw placement time, total radiation dose, and average effective radiation dose per screw were recorded and calculated. On the 10th day after surgery, postoperative X-ray and CT examinations were conducted to assess screw placement accuracy and facet joint violation. RESULTS: There were no significant differences in general characteristics among the three groups, ensuring comparability. Firstly, the average single screw placement time in the O-arm group was significantly shorter than that in the UVN group and X-ray group (P<0.05). Secondly, in terms of total radiation dose during surgery, for single-level MIS-TLIF, the O-arm group had a significantly higher radiation dose compared to the UVN group and X-ray group (P<0.05). However, for multi-level MIS-TLIF, the X-ray group had a significantly higher radiation dose than the O-arm group and UVN group (P<0.05). In terms of average single screw radiation dose, the O-arm group and X-ray group were similar (P>0.05), while the UVN group was significantly lower than the other two groups (P<0.05). Furthermore, no significant differences were found in screw placement assessment grades among the three groups (P>0.05). However, in terms of facet joint violation rate, the UVN group (10.3%) and O-arm group (10.7%) showed no significant difference (P>0.05), while the X-ray group (26.7%) was significantly higher than both groups (P<0.05). Moreover, in the UVN group, there were significant correlations between average single screw placement time and placement grade with BMI index (r = 0.637, P<0.05; r = 0.504, P<0.05), while no similar significant correlations were found in the O-arm and X-ray groups. CONCLUSION: UVN-guided screw placement in MIS-TLIF surgeries demonstrates comparable efficiency, visualization, and accuracy to O-arm navigation, while significantly reducing radiation exposure compared to both O-arm navigation and X-ray guidance. However, UVN may be influenced by factors like obesity, limiting its application.

"Sweet space" strategy for solvent system selection in countercurrent chromatography: A case study on separation of polyunsaturated fatty acids from borage oil.

This study presents a comprehensive strategy for the selection and optimization of solvent systems in countercurrent chromatography (CCC) for the effective separation of compounds. With a focus on traditional organic solvent systems, the research introduces a "sweet space" strategy that merges intuitive understanding with mathematical accuracy, addressing the significant challenges in solvent system selection, a critical bottleneck in the widespread application of CCC. By employing a combination of volume ratios and graphical representations, including both regular and trirectangular tetrahedron models, the proposed approach facilitates a more inclusive and user-friendly strategy for solvent system selection. This study demonstrates the potential of the proposed strategy through the successful separation of gamma-linolenic acid, oleic acid, and linoleic acid from borage oil, highlighting the strategy's effectiveness and practical applicability in CCC separations.

P53-induced GAP-43 Upregulation in Primary Cortical Neurons of Rats.

OBJECTIVES: In this study, we employed an in vitro culturing technique to investigate the impact of p53 on the modulation of growth-associated protein-43 (GAP-43) within the primary cortical neurons of rat specimens. METHODS: (1) Within the first 24 hours after birth, the bilateral cortex was extracted from newborn Wistar rats and primary cortical neurons were cultured and identified. (2) The changes in the mRNA and protein expressions of GAP-43 induced by p53 in rat primary cortical neurons cultured in vitro were identified utilizing real-time polymerase chain reaction and western blot techniques. RESULTS: (1) Lentiviral transfection of p53 within primary cortical neurons of rats elicited elevated levels of both mRNA and protein expressions of GAP-43, consequently culminating in a noteworthy augmentation of p53 expression. (2) The introduction of a p53 inhibitor in rat primary cortical neurons resulted in a reduction in both mRNA and protein expressions of GAP-43. CONCLUSION: Within primary rat cortical neurons, p53 has the potential to prompt an augmentation in both the transcriptional and protein expression levels of the GAP-43 protein.

[Comparison of screw placement guided by O-arm navigation and ultrasound volume navigation in minimally invasive transforaminal lumbar interbody fusion].

Objective: To compare the effectiveness of O-arm navigation and ultrasound volume navigation (UVN) in guiding screw placement during minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery. Methods: Sixty patients who underwent MIS-TLIF surgery for lumbar disc herniation between June 2022 and June 2023 and met the selection criteria were included in the study. They were randomly assigned to group A (screw placement guided by UVN during MIS-TLIF) or group B (screw placement guided by O-arm navigation during MIS-TLIF), with 30 cases in each group. There was no significant difference in baseline data, including gender, age, body mass index, and surgical segment, between the two groups ( P>0.05). Intraoperative data, including average single screw placement time, total radiation dose, and average single screw effective radiation dose, were recorded and calculated. Postoperatively, X-ray film and CT scans were performed at 10 days to evaluate screw placement accuracy and assess facet joint violation. Pearson correlation and Spearman correlation analyses were used to observe the relationship between the studied parameters (average single screw placement time and screw placement accuracy grading) and BMI. Results: The average single screw placement time in group B was significantly shorter than that in group A, and the total radiation dose of single segment and multi-segment and the average single screw effective radiation dose in group B were significantly higher than those in group A ( P<0.05). There was no significant difference in the total radiation dose between single segment and multiple segments in group B ( P>0.05), while the total radiation dose of multiple segments was significantly higher than that of single segment in group A ( P<0.05). No significant difference was found in the accuracy of screw implantation between the two groups ( P>0.05). In both groups, the grade 1 and grade 2 screws broke through the outer wall of the pedicle, and no screw broke through the inner wall of the pedicle. There was no significant difference in the rate of facet joint violation between the two groups ( P>0.05). In group A, both the average single screw placement time and screw placement accuracy grading were positively correlated with BMI ( r=0.677, P<0.001; r=0.222, P=0.012), while in group B, neither of them was correlated with BMI ( r=0.224, P=0.233; r=0.034, P=0.697). Conclusion: UVN-guided screw placement in MIS-TLIF surgery demonstrates comparable efficiency, visualization, and accuracy to O-arm navigation, while significantly reducing radiation exposure. However, it may be influenced by factors such as obesity, which poses certain limitations.

Development of a general separation strategy by countercurrent chromatography using sanshools from Zanthoxylum bungeanum oleoresin as a case study.

Three kinds of sanshools were separated from Zanthoxylum bungeanum oleoresin by high-speed countercurrent chromatography. Sanshools are a series of amide compounds extracted from the Zanthoxylum bungeanum. Due to similar structures, polarities, and dissociation constants, it was challenging to select an appropriate solvent system for their complete separation by countercurrent chromatography. To address this challenge, a solvent-system-selection strategy was proposed to identify a relatively suitable solvent system. Additionally, a separation procedure incorporating multi-elution modes selection was established to separate similar compounds in a logical order. Ultimately, a solvent system comprising n-hexane:ethyl acetate:methanol:water in a ratio of 19:1:1:5.67 was selected. Three amide compounds with high purity were obtained through the use of recycling elution mode to improve separation resolution: hydroxy-ε-sanshool (8.4 mg; purity: 90.64%), hydroxy-α-sanshool (326.4 mg; purity: 98.96%), and hydroxy-ß-sanshool (71.8 mg; purity: 98.26%) were obtained from 600 mg sanshool crude extract. The summarized solvent-system-selection strategy and separation procedure incorporating multi-elution modes may instruct countercurrent chromatography users, particularly novices, seeking to separate compounds with highly similar chemical properties.

Using Drosophila Two-Choice Assay to Study Optogenetics in Hands-On Neurobiology Laboratory Activities.

Optogenetics has made a significant impact on neuroscience, allowing activation and inhibition of neural activity with exquisite spatiotemporal precision in response to light. In this lab session, we use fruit flies to help students understand the fundamentals of optogenetics through hands-on activities. The CsChrimson channelrhodopsin, a light-activated cation channel, is expressed in sweet and bitter sensory neurons. Sweet sensory neurons guide animals to identify nutrient-rich food and drive appetitive behaviors, while bitter sensory neurons direct animals to avoid potentially toxic substances and guide aversive behavior. Students use two-choice assays to explore the causality between the stimulation activation of these neurons and the appetitive and avoidance behaviors of the fruit flies. To quantify their observations, students calculate preference indices and use the Student's t-test to analyze their data. After this lab session, students are expected to have a basic understanding of optogenetics, fly genetics, sensory perception, and how these relate to sensory-guided behaviors. They will also learn to conduct, quantify, and analyze two-choice behavioral assays.

Tumor necrosis factor-α inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation.

BACKGROUND: Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation in vitro, which seriously limits research on ADSCs and their application. AIM: To improve the chondrogenic differentiation efficiency of ADSCs in vitro, and optimize the existing chondrogenic induction protocol. METHODS: Tumor necrosis factor-alpha (TNF-α) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-κB) signaling pathway. RESULTS: In this study, we found that the levels of TNF-α and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-α then bound to its receptor and activated the NF-κB pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-α with its inhibitors etanercept (1 µg/mL) or infliximab (10 µg/mL) significantly restored matrix formation. CONCLUSION: Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

Evaluating the effect of methotrexate on the rate of renal fibrosis by elastography and fibrosis-related gene expression.

Methotrexate is mainly used to treat diseases such as rheumatoid arthritis (RA), but its potential for nephrotoxicity has always been a significant concern on the use of this medication. This study aimed to determine the rate of renal fibrosis using transient elastography and its relationship with cumulative dose and duration of drug use in patients with rheumatoid arthritis treated with methotrexate. TGFß gene expression was also assessed for further evaluation. Patients with rheumatoid arthritis who received methotrexate for more than six months were included. Renal fibrosis was determined by measuring the stiffness of the kidney by elastography (FiberScan Device). RA patients were divided into two groups based on kidney stiffness measurement with and without renal fibrosis, and demographic, clinical, and biochemical parameters were compared to investigate the relationship between cumulative dose and duration of methotrexate treatment and renal fibrosis. Also, in this study, 50 controls (healthy people) and 50 cases (RA patients) were used to evaluate the expression of the TGFß gene by real-time PCR method. The existence of kidney fibrosis was observed in 10 patients. There was no significant relationship between renal fibrosis and the cumulative dose (P = 0.21) and duration of methotrexate (P = 0.30). Multivariate regression analysis showed that the chances of developing renal fibrosis in patients increase with increasing serum ALT levels (P = 0.01). The results of the TGFß gene expression showed that the expression of this gene in the group of RA patients with fibrosis was higher than the control group (healthy people) and the group of RA patients without fibrosis (P <0.01). These results showed that evaluation of renal fibrosis by elastography method is recommended for scanning RA patients while they are being treated with methotrexate, which is also confirmed by the results of the fibrosis-related-gene expression.

Effects of enteral nutrition semi-curing feeding on nutritional diarrhoea improvement in the patients with severe stroke.

OBJECTIVE: The present study aims to explore the effects of enteral nutrition (EN) semi-curing feeding on nutritional diarrhoea in the patients with stroke. METHODS: The patients admitted to the neurological intensive care unit of a tertiary care hospital with stroke- and EN-related diarrhoea between May 2019 and October 2020 were included in the study. The 60 patients, who met the inclusion criteria were divided into the two groups (30 patients each), the experimental group (EN solution+probiotics+90 ml of pectin) and the control group (EN solution+probiotics), in accordance with the random number table method. The stool number, total stool amount, perineal skin score, and time required to achieve the nutritional target of each patient were recorded at admission and on days 1, 3, and 7 of pectin intervention. The lymphocyte count and the haemoglobin, serum pre-albumin (PA), and total cholesterol (TC) levels were measured in order to assess the patients' nutritional statuses. RESULTS: The stool number and total stool amount on days 1 and 3 of pectin intervention in the experimental group were better than in the control group; the differences were statistically significant (p <0.05). On day 7 of the intervention, the stool number, total stool amount, and perineal skin score had decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). Furthermore, the PA levels increased, and TC levels decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). On day 3 of the intervention, the PA levels in the experimental group were increased compared to the control group; the difference was statistically significant (p <0.05). CONCLUSION: EN semi-curing feeding could improve EN-related diarrhoea and nutritional status levels in patients with stroke (Tab. 3, Ref. 9).

A case of 15q11-q13 duplication syndrome and literature review.

BACKGROUND: The chromosomal 15q11-q13 regions are structurally complex, and their abnormalities are associated with various neuropsychiatric disorders, including autism spectrum disorder (ASD), epilepsy, Angelman syndrome, and Prader-Willi syndrome. CASE DESCRIPTION: A 6-year-old child was admitted to the hospital as a result of an "epileptic status" showing ASD, intractable epilepsy, and total developmental retardation. Chromosome gene detection showed repetitive variation in the 15q11-q13 regions, and the video electroencephalogram was abnormal. Although children are currently given antiepileptic treatment and rehabilitation training, intermittent seizures can still occur. CONCLUSION: The clinical phenotypes of 15q11-q13 repetitive syndrome are complex, and vary in severity. Children with intractable epilepsy, ASD, and language and motor retardation should be considered to have this syndrome, which requires confirmation by multiplex ligation-dependent probe amplification and gene detection. These approaches can enable early rehabilitation treatment and improve the patients' quality of life.

Case Report: A Case Report and Literature Review of 3p Deletion Syndrome.

Objective: The aim of the present study is to explore the clinical and genetic characteristics of 3p deletion syndrome to improve clinicians' understanding of the disease. Methods: The clinical manifestations, process of diagnosis and treatment, and genetic characteristics of an individual case of 3p deletion syndrome were analyzed. CNKI, Wanfang Data, and the Biomedical Literature Database (PubMed) were searched. The search time limit, using "3p deletion syndrome" and "BRPF1" as keywords, was from the creation of the database up to June 2020. Related data were reviewed. Results: The proband was a male child with general developmental and intellectual disabilities, special facial features and congenital heart disease. The child was the parents' first pregnancy and first born. Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene; thus, the patient was diagnosed with 3p deletion syndrome. At the time of diagnosis, the child was 1 year of age and was responding to comprehensive rehabilitation training. A total of 29 well-documented cases were found in the literature, of which 19 cases had an onset within 1 year of birth, and mainly manifested with mental and motor development disabilities and abnormal facial features, with different gene deletions, depending on the size and location of the 3p deletion. Conclusion: The genetic test results of the child in this study indicated a heterozygous deletion of the BRPF1 gene on the short arm of chromosome 3, which was a unique feature of this study, since it was rarely mentioned in other reports of 3p deletion syndrome. The clinical phenotype of this syndrome is complex as it can include intellectual and motor development backwardness, low muscle tone, certain abnormal facial features (low hairline, bilateral ptosis, widely spaced eyes, a forward nose, left ear auricle deformity, a high-arched palate, a small jaw), and the deformation of systems such as the gastrointestinal tract and the urinary tract malformation or symptoms of epilepsy. As clinical manifestations can be relatively mild, the syndrome is easy to miss or misdiagnose. Clinical workers need to be aware of this disease when they find that children have special features, such as stunted growth, low muscle tone or ptosis, and it needs to be diagnosed through genetic testing. Most children are able to develop certain social skills after rehabilitation treatment.

Stabilizing a laser frequency by the Pound-Drever-Hall technique with an acousto-optic modulator.

We develop and demonstrate a method of optical phase modulation in the Pound-Drever-Hall (PDH) technique. The phase modulation in this paper is realized by an acousto-optic modulator (AOM) operating in the Bragg diffraction regime. In this process, a light beam separated from a laser (780 nm) is sent through the AOM twice and coupled to a high finesse Fabry-Perot cavity. Then, the light power coupling into the cavity is stabilized by modulating the optical amplitude with this AOM. The coupling light power is stabilized to a level of 10-3. In the meantime, the PDH error signal is obtained by modulating the optical phase with the same AOM. After the error signal is fed back to the laser current, the laser linewidth is suppressed to approximately 907.91 Hz. This method of phase modulation is simple and convenient, and we believe it can be widely used in modulation transfer spectroscopy and frequency-modulation sideband spectroscopy.

Establishment and Verification of Multiaxis Fatigue Life Prediction Model.

A fatigue life prediction model with multiaxis load is proposed. The model introduces a new effective cyclic parameter, equivalent stress on the critical surface, to modify the Suntech model. The new damage parameters are not related to empirical constants, hence more applicable for practical application in engineering. The multiaxis fatigue test was carried out with high-strength aluminum alloy 7075-T651, and the multiaxis fatigue life prediction of the test piece was conducted with the finite element software. The experiment result shows that the model proposed is effective for predicting the fatigue life under multiaxis load.

Ginsenoside Rg3 inhibits pulmonary fibrosis by preventing HIF-1α nuclear localisation.

BACKGROUND: Excessive fibroblast proliferation during pulmonary fibrosis leads to structural abnormalities in lung tissue and causes hypoxia and cell injury. However, the mechanisms and effective treatment are still limited. METHODS: In vivo, we used bleomycin to induce pulmonary fibrosis in mice. IHC and Masson staining were used to evaluate the inhibitory effect of ginsenoside Rg3 in pulmonary fibrosis. In vitro, scanning electron microscopy, transwell and wound healing were used to evaluate the cell phenotype of LL 29 cells. In addition, biacore was used to detect the binding between ginsenoside Rg3 and HIF-1α. RESULTS: Here, we found that bleomycin induces the activation of the HIF-1α/TGFß1 signalling pathway and further enhances the migration and proliferation of fibroblasts through the epithelial mesenchymal transition (EMT). In addition, molecular docking and biacore results indicated that ginsenoside Rg3 can bind HIF-1α. Therefore, Ginsenoside Rg3 can slow down the progression of pulmonary fibrosis by inhibiting the nuclear localisation of HIF-1α. CONCLUSIONS: This finding suggests that early targeted treatment of hypoxia may have potential value in the treatment of pulmonary fibrosis.

Efficacy and safety of omalizumab in children with moderate-to-severe asthma: a meta-analysis.

OBJECTIVE: To assess the efficacy and safety of omalizumab in children with moderate-to-severe asthma. DATA SOURCES: We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (RCTs ) (inception to January 2020). STUDY SELECTIONS: All RCTs which were conducted in childhood and adolescence with asthma and compared the efficacy or safety of omalizumab were adopted. RESULTS: Three studies with four publications including 1380 pediatric patients met our criteria. For children with moderate-to-severe asthma, omalizumab decreased asthma exacerbations rate (OR 0.51, 95% CI: 0.44-0.58, p < 0.001) compared with placebo with no evidence of heterogeneity. Omalizumab reduced the rate of asthma exacerbations 0.58) with treatment period ≥30 weeks (p for heterogeneity = 0.03). Omalizumab treated patients had an excellent or good response rate of treatment effectiveness assessed by physicians (2.75, 2.45-3.09) and a bigger reduction in the dosage of inhaled corticosteroid (ICS) at the end of follow-up. For children with severe asthma, omalizumab also reduced the likelihood of asthma exacerbations and increased the odd of treatment effectiveness rated as excellent or good. Patients receiving omalizumab had a lower incidence of severe adverse events (0.36, 0.22-0.57). CONCLUSIONS: These findings suggested that omalizumab had beneficial effects on moderate-to-severe asthma in children. Patients may benefit more from long-term use of omalizumab. In addition, omalizumab reduces the rate of serious adverse events requiring hospitalizations.

[Blepharoptosis and dysarthria in a boy aged 2 years].

A boy, aged 2 years and 4 months, had a sudden onset of blepharoptosis of the right eyelid, accompanied by the mouth deviated to the right side, drinking cough, nystagmus, and developmental regression. Cranial MRI showed softening lesions formed after infarction of the right dorsolateral medulla oblongata, while head CT angiography showed no imaging of the proximal part of the V4 segment of the right vertebral artery. The child was diagnosed with dorsolateral medulla oblongata syndrome and was treated with gamma globulin to regulate immune function, with mannitol to reduce neuronal edema, with low-molecular-weight heparin sodium to improve local hypercoagulation of occluded blood vessels, with hyperbaric oxygen to improve local ischemia and hypoxia and promote the recovery of brain function, and with neuromuscular electrical stimulation to promote the recovery of neuromuscular function. Before discharge, only mild right ataxia and Horner syndrome remained. This article reports the first case of infantile dorsolateral medulla oblongata syndrome and provides experience for the diagnosis and treatment of the disease.

Distal radius fracture malunion in an adolescent patient treated with osteotomy and autologous iliac bone grafting: A case report.

RATIONALE: Adolescent wrist trauma can cause epiphyseal dysplasia and even distal radius deformity malunion. At present, there is no uniform treatment standard for the malunion of the distal radius of adolescents. Osteotomy and autologous bone grafting are currently one of the effective ways to treat the disease. We treated an adolescent patient with distal radius deformity malunion, and used this surgical method to treat the patient and achieved satisfactory results. PATIENT CONCERNS: A 16-year-old boy suffered from a serious distal radius deformity after trauma of the left wrist 8 years ago. DIAGNOSES: Physical examination, X-rays examination, high-resolution computed tomography scan, and 3-dimensional reconstruction images of the affected limb helped us diagnose the distal radius fracture malunion. INTERVENTIONS: The fracture malunion was treated by osteotomy and autologous iliac bone grafting. OUTCOMES: At the 2-year follow-up, wrist flexion returned to 68°, wrist dorsiflexion to 55°, radial deviation to 14°, ulnar deviation to 12°, forearm pronation to 75°, supination to 67°. Grip strength increased to 35.1 kg after 2 years of operation, recovered to 87% of the uninjured side. Quick DASH score at 2-year follow-up was 9. No complication, such as nonunion or infection, was observed. LESSONS: This rare case provides valuable insights for hand surgeons. High-resolution computed tomography scan and 3-dimensional reconstruction can help us effectively diagnose wrist diseases. Small lesions on the articular surface of the distal radius will change the position and function of the wrist joint, and cause traumatic arthritis of the wrist joint. Therefore, it is very important to reconstruct the normal structure of the distal radius articular surface. Osteotomy and autologous iliac bone grafting are effective treatments for serious distal radius fracture malunion in the adolescent patient. During the operation, care should be taken to protect the osteoepiphysis to avoid bone dysplasia.

Brain Endothelial Cells Regulate Glucagon-Like Peptide 1 Entry Into the Brain via a Receptor-Mediated Process.

Glucagon-like peptide 1 (GLP-1) in addition to regulating glucose-dependent insulin and glucagon secretion exerts anorexic and neuroprotective effects. While brain-derived GLP-1 may participate in these central actions, evidence suggests that peripherally derived GLP-1 plays an important role and GLP-1 analogs are known to cross the blood brain barrier. To define the role of brain microvascular endothelial cells in GLP-1 entry into the brain, we infused labeled GLP-1 or exendin-4 into rats intravenously and examined their appearance and protein kinase A activities in various brain regions. We also studied the role of endothelial cell GLP-1 receptor and its signaling in endothelial cell uptake and transport of GLP-1. Systemically infused labeled GLP-1 or exendin-4 appeared rapidly in various brain regions and this was associated with increased protein kinase A activity in these brain regions. Pretreatment with GLP-1 receptor antagonist reduced labeled GLP-1 or exendin-4 enrichment in the brain. Sub-diaphragmatic vagus nerve resection did not alter GLP-1-mediated increases in protein kinase A activity in the brain. Rat brain microvascular endothelial cells rapidly took up labeled GLP-1 and this was blunted by either GLP-1 receptor antagonism or protein kinase A inhibition but enhanced through adenylyl cyclase activation. Using an artificially assembled blood brain barrier consisting of endothelial and astrocyte layers, we found that labeled GLP-1 time-dependently crossed the barrier and the presence of GLP-1 receptor antagonist blunted this transit. We conclude that GLP-1 crosses the blood brain barrier through active trans-endothelial transport which requires GLP-1 receptor binding and activation.

Multi-start heuristic approaches for one-to-one pickup and delivery problems with shortest-path transport along real-life paths.

The One-to-one Pickup and Delivery Problem with Shortest-path Transport along Real-life Paths (OPDPSTRP) is presented in this paper. It is a variation of the One-to-one Pickup and Delivery Problem (OPDP), which is common in daily life, such as the Passenger Train Operation Plans (PTOP) and partial Taxi-sharing Problem. Unlike the classical OPDP, in the OPDPSTRP, (1) each demand must be transported along the shortest path according to passengers/shippers requirements, and (2) each vehicle should travel along a real-life path. First, six route structure rules are proposed for the OPDPSTRP, and a kind of Mixed-Integer Programming (MIP) models is formulated for it. Second, A Variable Neighborhood Descent (VND), a Variable Neighborhood Research (VNS), a Multi-Start VND (MS_VND) and a Multi-Start VNS (MS_VNS) with five neighborhood operators has been developed to solve the problem. Finally, The Gurobi solver, the VND, the VNS, the MS_VND and the MS_VNS have been compared with each other by 84 random instances partitioned in small size connected graphs, medium size connected graphs and large size connected graphs. From the test results we found that solutions generated by these approaches are often comparable with those found by the Gurobi solver, and the solutions found by these approaches are better than the solutions found by the Gurobi solver when solving instances with larger numbers of demands. In almost all instances, the MS_VND significantly outperforms the VND and the VNS in terms of solution quality, and outperforms the MS_VNS both in terms of solution quality and CPU time. In the instances with large numbers of demands, the MS_VND is still able to generate good feasible solutions in a reasonable CPU time, which is of vital practical significance for real-life instances.