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Background Far from now, there is still a lack of studies on dexamethasone combined with ropivacaine for ultrasound-guided thoracic paravertebral block (TPVB). Our study aims to observe the analgesic effect of 0.2mg/kg dexamethasone combined with ropivacaine for TPVB on patients undergoing thoracoscopic lobectomy to evaluate postoperative analgesic effect of the compound and prgnosis of patients. Methods 92 patients who underwent thoracoscopic lobectomy from August 2020 to March 2021 were randomly divided into ropivacaine group (group R) and dexamethasone combined with ropivacaine group (group RD), 46 cases in each group. The group R was performed thoracic paravertebral block with 20ml 0.5% ropivacaine, then the group RD was injected with 20ml of 0.2mg/kg dexamethasone and 0.5% ropivacaine mixture, and general anesthesia induction was performed 30 minutes after the completion of thoracic paravertebral nerve block. The onset time and width of sensory block were observed and recorded. VAS scores were recorded at 1h(T1), 6h(T2), 12h(T3) and 24h(T4). Additional analgesic and sedative drugs for salvage use within 24 hours after operation were recorded. The preoperative fasting glucose level and the postoperative one-day fasting glucose level were recorded. The incidence of side-effects such as skin pruritus, nausea and vomiting were recorded. The extubation time of tracheal intubation and total hospital stay were recorded. Results There was no significant difference in the onset time and width of sensory block between the two groups(P > 0.05); The VAS scores at T1, T2, T3 and T4 in group RD were significantly lower than group R(P < 0.05); Compared with group R, the proportion of patients in group RD who received additional morphine rescue analgesia within 24 hours after operation was significantly lower(P P > 0.05); The incidence of postoperative nausea and vomiting was similar between the two groups(P > 0.05); There was no significant difference between the preoperative fasting blood glucose and the postoperative one-day fasting blood glucose in group R(P > 0.05); The fasting blood glucose showed an increase on the first day after operation than that before operation in group RD(P P P > 0.05). Conclusion 0.2mg/kg dexamethasone combined with ropivacaine for TPVB can significantly enhance the analgesic effect of ropivacaine in nerve blocks, provide effective and comprehensive postoperative analgesia for patients undergoing thoracoscopic lobectomy, shorten extubation of tracheal tube after operation, and with no increasing incidence of side effects, but exhibit rare influence on the extent of nerve block and total length of hospital stay. Clinical trial registration: No. ChiCTR2000033956, registrated at the Chinese Clinical Trial Registry, principal investigator: Xiaopei Gao, date of registration: 18/06/2020.

Innovations in endoscopy have brought about some impressive improvements in diagnosing and treating gastroesophageal reflux disease (GERD). GERD, as one of the most prevalent gastrointestinal disorders in the world, has always been on the cutting edge of endoscopic interventions. A primary diagnosis of GERD is based on symptoms and an initial trial of proton-pump inhibitor (PPI) therapy, which is devoid of adequately instructive value for therapeutic strategies. Endoscopy and optional biopsies can be used to directly observe and determine the abnormal structural and pathophysiological damage in the esophagus. The emergence of minimally invasive endoscopic therapy fills the gap between patients who are reluctant or insensitive to PPIs and candidates who are not indicated for surgical anti-reflux fundoplication. In this review, we discuss the utility of endoscopy and biopsy in patients with persistent GERD-related manifestations after proper medical anti-reflux treatment. Moreover, we portray a landscape of four current endoscopic GERD therapies and clarify the merits and disadvantages of each technique. Future research needs to concentrate on stratifying GERD patients based on personal conditions and elucidating the primary pathophysiology of GERD.

Dentition defects or missing are common diseases threatening human health. The dental implant technology is an effective way to repair dentition defects. Titanium and titanium alloy implants are widely used in clinical practice because of their good biocompatibility, corrosion resistance, and high mechanical strength. In this study, anodic oxidation was used to prepare titanium dioxide nanotubes with different diameters. Due to the strong adsorption capacity of the nanotube structure, the nanotube was loaded with icariin, and then the titanium dioxide nanotubes loaded with icariin (NTx + ICy) were applied in osteogenesis and osseointegration experiment. It was found that the prepared titanium dioxide nanotube wall was smooth. The diameters of the nanotubes prepared at 10 V, 20 V, and 28 V were 30 nm, 50 nm and 75 nm, respectively. The proportion of icariin was varied, and the most sustained release time of icariin was three days, and the sustained release amount was relatively large on the first day. At each time point, the number of cells adhered to the pure titanium sheets and 10 V-treated nanotubes-Icariin was large and notably higher than 30 V-treated nanotube-Icariin. The patients involved were subjected to puncture to obtain bone marrow stem cells. It was found that the NTx + ICy materials promoted the osteoblast proliferation. Further, clinical observation found that the composite titanium dioxide nanotube materials can stimulate macrophages to create a powerful bone immune microenvironment and accelerate the process of osseointegration.

Although scholars and practitioners have highlighted the significance of students’ attitudes for their future employment, few empirical examinations have attempted to determine the potential association between students’ future orientation and their perceived employability. Thus, drawing on career construction theory, we test the positive effect of students’ future orientation on their perceived employability by exploring the mediator of problem-based learning and the moderators of job market knowledge and proactive personality. Collecting our data via a time-lagged design (N = 368), we have found that the positive association between future orientation and employability is mediated by problem-based learning. Our moderation analyses further revealed that job market knowledge positively moderates the relationship between future orientation and problem-based learning and that students’ proactive personality positively moderates the relationship between problem-based learning and perceived employability.

BACKGROUND: Currently, antireflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) are the most commonly used minimally invasive antireflux therapies. To date, there have not been any reports comparing ARMS and SRF. Our aim was to compare the clinical efficacies of these two therapeutic methods. METHODS: We analyzed data from gastroesophageal reflux disease (GERD) patients, including 39 who received ARMS treatment and 30 who received SRF treatment between January 2020 and May 2021. Symptom control, gastroesophageal reflux disease questionnaire (GERDQ) score, gastroesophageal reflux disease health-related quality of life (GERD-HRQL) score, proton pump inhibitor (PPI) withdrawal, and PPI reduction were analyzed and compared. RESULTS: After 6 months of follow-up, the results showed that both therapies were effective in improving symptoms and quality of life. No difference was found between the ARMS group and SRF group in GERDQ score, GERD-HRQL score, PPI withdrawal rate, or PPI reduction rate (P>0.05). There was no significant difference in the PPI withdrawal rate between the two therapies among patients with gastroesophageal flap valve (GEFV) grade II and grade III (P>0.05), but the PPI withdrawal rate in the ARMS group was significantly higher than that in the SRF group among patients with GEFV grade IV (P

Disruption of alveolar-capillary barriers is a major complication of high-volume mechanical ventilation referred to as "ventilator-induced lung injury." The stretching force in alveoli is transmitted to endothelial cells, increasing the tension on underlying endothelial plasma membrane. The mechanosensor Piezo1, a plasma membrane cation channel, was inducibly deleted in endothelial cells of mice (Piezo1iEC-/-), which allowed us to study its role in regulating the endothelial barrier response to alveolar stretch. We observed significant increase in lung vascular permeability in Piezo1iEC-/- mice as compared with control Piezo1fl/fl mice in response to high-volume mechanical ventilation. We also observed that human lung endothelial monolayers depleted of Piezo1 and exposed to cyclic stretch had increased permeability. We identified the calcium-dependent cysteine protease calpain as a downstream target of Piezo1. Furthermore, we showed that calpain maintained stability of the endothelial barrier in response to mechanical stretch by cleaving Src kinase, which was responsible for disassembling endothelial adherens junctions. Pharmacological activation of calpain caused Src cleavage and thereby its inactivation, and it restored the disrupted lung endothelial barrier seen in Piezo1iEC-/- mice undergoing high-volume mechanical ventilation. Our data demonstrate that downregulation of Piezo1 signaling in endothelium is a critical factor in the pathogenesis of ventilator-induced lung injury, and thus augmenting Piezo1 expression or pharmacologically activating Piezo1 signaling may be an effective therapeutic strategy.

Endoscopic grading of gastroesophageal flap valve (GEFV) is simple and reproducible and offers useful information for reflux activity. To investigate the potential correlation between GEFV grading and reflux finding score (RFS) in patients with laryngopharyngeal reflux disease (LPRD), 225 consecutive Patients with suspected LPRD who underwent both routine upper gastrointestinal endoscopy and laryngoscope were enrolled in our study. Patients with a RFS of more than 7 were diagnosed with LPRD. The GEFV was graded as I through IV according to Hill’s classification and was classified into two groups: normal GEFV group (grades I and II) and the abnormal GEFV group (grades III and IV). The percent of GEFV grades I to IV was 39.1%, 39.1%, 12.4%, and 9.3%, respectively. Age was significantly related to an abnormal GEFV (p = 0.002). Gender, BMI, smoke and alcohol were not related to GEFV grade. Fifty-one patients (22.67%) had positive RFS. Reflux finding scores were higher in GEFV grades III and IV than I and II (p

BACKGROUND: Colorectal cancer is among the most prominent malignant tumors endangering human health, with affected populations exhibiting an increasingly younger trend. The Kirsten ras (KRAS) gene acts as a crucial regulator in this disease and influences multiple signaling pathways. In the present study, the KRAS gene mutation-induced alteration of intestinal flora in colorectal cancer patients was explored, and the intestinal microbes that may be affected by the KRAS gene were examined to provide new insights into the diagnosis and treatment of colorectal cancer. METHODS: Deoxyribonucleic acid (DNA) was extracted from 177 colorectal cancer patients in our hospital. The mutation of the KRAS gene was subsequently detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), and survival analysis was performed. Moreover, genomic DNA was extracted from the fecal microbes in 30 of these patients, and the differences in the intestinal flora between mutation and non-mutation groups were evaluated using linear discriminant analysis (LDA) Effect size (LEfSe) analysis. RESULTS: KRAS gene mutation substantially affected the distant metastasis of colorectal cancer, and the survival prognosis in the non-mutation group was significantly superior compared to the mutation group. The mutation group had a notably higher prevalence of microbes including Roseburia, Parabacteroides, Metascardovia, Staphylococcus, Staphylococcaceae, and Bacillales than the non-mutation group. The presence of microbes in the non-mutation group, such as Clostridiales, Bacteroidetes, Lachnospiraceae, Coprococcus, and Ruminococcaceae was markedly higher than in the mutation group. Firmicutes were negatively correlated with the presence of Actinomyces and Bacteroidetes, while Bacteroidetes were positively associated with the level of Actinomyces. CONCLUSIONS: In colorectal cancer, KRAS gene mutation can remarkably affect the survival prognosis and change the composition and abundance of intestinal flora, such as Roseburia, Parabacteroides, Metascardovia, Staphylococcus, and Bacillales, thereby influencing tumor development.

Macrophages demonstrate remarkable plasticity that is essential for host defense and tissue repair. The tissue niche imprints macrophage identity, phenotype and function. The role of vascular endothelial signals in tailoring the phenotype and function of tissue macrophages remains unknown. The lung is a highly vascularized organ and replete with a large population of resident macrophages. We found that, in response to inflammatory injury, lung endothelial cells release the Wnt signaling modulator Rspondin3, which activates β-catenin signaling in lung interstitial macrophages and increases mitochondrial respiration by glutaminolysis. The generated tricarboxylic acid cycle intermediate α-ketoglutarate, in turn, serves as the cofactor for the epigenetic regulator TET2 to catalyze DNA hydroxymethylation. Notably, endothelial-specific deletion of Rspondin3 prevented the formation of anti-inflammatory interstitial macrophages in endotoxemic mice and induced unchecked severe inflammatory injury. Thus, the angiocrine–metabolic–epigenetic signaling axis specified by the endothelium is essential for reprogramming interstitial macrophages and dampening inflammatory injury. The angiocrine Rspondin3 is produced by endothelial cells (ECs) and controls growth and development. Malik and colleagues show that lung ECs produce Rspondin3 following injury and specifically direct interstitial macrophages into an anti-inflammatory and wound-healing program.

BACKGROUNDClinical study indicated that infusion of dexmedetomidine without loading dose intraoperative provided smooth and haemodynamically stable emergence, and improved quality of recovery with fewer postoperative side effects and analgesic requirements 9 . The objective is to determine remifentanil-propofol combined with dexmedetomidine during general anesthesia would decrease the incidence and severity of postoperative emergence agitation, anxiety and depression, and without effect on the cognitive dysfunction in elder patients.METHODS120 elder patients scheduled for ureteroscopic holmium laser lithotripsy were randomly allocated to PR group administered the normal saline, and PRD group administered dexmedetomidine 0.4 µg.Kg -1 .h -1 intravenously after induction of anesthesia, and stopped 30 minutes before the end of surgery. The primary outcome was the scores of richmond agitation sedation, mini mental state examination, state-trait anxiety inventory, zung self-Rating depression scale, and the arabic numeral memory. The secondary outcome was the duration of surgery, and time to spontaneous respiration, recovery and extubation.RESULTSThe dosage of propofol and remifentanil decreased more significantly in PRD group ( P< 0.001). The RASS scores in the PRD group was significantly lower than in PR group at t 1-3 ( P< 0.001). The MMSE scores were lower at T 1 - 2 in two groups ( P< 0.001). Compared to PR group, the ZSDS scores and STAI scores at T 1 - 2 were lower in PRD group ( P

Inflammatory tissue injury such as acute lung injury (ALI) is a disorder that leads to respiratory failure, a major cause of morbidity and mortality worldwide. Excessive neutrophil influx is a critical pathogenic factor in the development of ALI. Here, we identify the subset of neutrophils that is responsible for ALI and lethality in polymicrobial sepsis. The pro-inflammatory neutrophil subpopulation was characterized by its unique ability to endocytose albumin nanoparticles (ANP), upregulation of pro-inflammatory cytokines and chemokines as well as the excessive production of reactive oxygen species (ROS) in models of endotoxemia and septicemia. ANP delivery of the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, to the susceptible subset of neutrophils, prevented ALI and mortality in mice subjected to polymicrobial infection. Targeted inhibition of Syk in ANP-susceptible neutrophils had no detrimental effect on neutrophil-dependent host defense because the subset of ANPlowneutrophils effectively controlled polymicrobial infection. The results show that neutrophil heterogeneity can be leveraged therapeutically to prevent ALI without compromising host defense.

Unchecked inflammation is a hallmark of inflammatory tissue injury in diseases such as acute respiratory distress syndrome (ARDS). Yet the mechanisms of inflammatory lung injury remain largely unknown. Here we showed that bacterial endotoxin lipopolysaccharide (LPS) and cecal ligation and puncture-induced (CLP-induced) polymicrobial sepsis decreased the expression of transcription factor cAMP response element binding (CREB) in lung endothelial cells. We demonstrated that endothelial CREB was crucial for VE-cadherin transcription and the formation of the normal restrictive endothelial adherens junctions. The inflammatory cytokine IL-1β reduced cAMP generation and CREB-mediated transcription of VE-cadherin. Furthermore, endothelial cell-specific deletion of CREB induced lung vascular injury whereas ectopic expression of CREB in the endothelium prevented the injury. We also observed that rolipram, which inhibits type 4 cyclic nucleotide phosphodiesterase-mediated (PDE4-mediated) hydrolysis of cAMP, prevented endotoxemia-induced lung vascular injury since it preserved CREB-mediated VE-cadherin expression. These data demonstrate the fundamental role of the endothelial cAMP-CREB axis in promoting lung vascular integrity and suppressing inflammatory injury. Therefore, strategies aimed at enhancing endothelial CREB-mediated VE-cadherin transcription are potentially useful in preventing sepsis-induced lung vascular injury in ARDS.

Science and technology innovation policies have been considered as effective policy tools in promoting regional innovation. This paper used content analysis method to analyze 321 pieces of science and technology policies published from 2006 to 2018. Structures of the policy social networks had been analyzed and discussed, and the main points and emphasis of the science and technology policy system of China’s Yangtze River Delta region had been revealed. Results indicated that Shanghai, Jiangsu, Zhejiang and Anhui’s science and technology policy system structures were relatively consistent, while the development paths were different, and the content of industrial policy of four provinces had a serious homogenization problem.

Although servant leadership has been acknowledged as an important predictor of employees&rsquo, behavioral outcomes in the service industry, there is still no cohesive understanding of the positive association between servant leadership and employees&rsquo, customer-oriented behavior (COB). This research, drawing on cognitive affective processing system theory (CAPS), empirically investigates the influence of servant leadership on employees&rsquo, COB by exploring two mediators (i.e., organizational identification and vitality). We conducted two studies in China, using a cross-sectional design to survey employees in service-oriented technical organizations (Study 1) and a time-lagged design to survey hospitality employees with frontline service jobs in star-level hotels (Study 2). Across both samples, we found that servant leadership enhanced employees&rsquo, COB by simultaneously increasing their organizational identification and vitality. We discuss the implications of these results for future research and practice.

In this study, an eco-olivine nanosilica is produced from natural olivine, and then used as an alternative silicate source in synthesizing the silicate-based alkali activator. The effects of silicate origin and dosage on activator characteristics, fresh behaviors, gel structure, strength, porosity, and shrinkage are investigated. The results indicate that the soluble silica content in the alternative activators is above 98%; compared with the traditional waterglass-based mixes, the nanosilica-derived ones exhibit similar behaviors in the early age reaction, gel structure, and mechanical properties. As some important engineering properties, nanosilica-based mixtures also exhibit increased workability, prolonged setting time, slightly increased porosity, and shrinkage. Thus, by using this alternative silica source in alkali-activated materials, a more sustainable product with less cost and carbon emission can be achieved, and with comparable key performances.

Acute lung injury is a leading cause of death in bacterial sepsis due to the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of proinflammatory leukocytes, and intractable hypoxemia. Pyroptosis is a form of programmed lytic cell death that is triggered by inflammatory caspases, but little is known about its role in EC death and acute lung injury. Here, we show that systemic exposure to the bacterial endotoxin lipopolysaccharide (LPS) causes severe endothelial pyroptosis that is mediated by the inflammatory caspases, human caspases 4/5 in human ECs, or the murine homolog caspase-11 in mice in vivo. In caspase-11–deficient mice, BM transplantation with WT hematopoietic cells did not abrogate endotoxemia-induced acute lung injury, indicating a central role for nonhematopoietic caspase-11 in endotoxemia. Additionally, conditional deletion of caspase-11 in ECs reduced endotoxemia-induced lung edema, neutrophil accumulation, and death. These results establish the requisite role of endothelial pyroptosis in endotoxemic tissue injury and suggest that endothelial inflammatory caspases are an important therapeutic target for acute lung injury.

Cytosolic DNA acts as a universal danger-associated molecular pattern (DAMP) signal; however, the mechanisms of self-DNA release into the cytosol and its role in inflammatory tissue injury are not well understood. We found that the internalized bacterial endotoxin lipopolysaccharide (LPS) activated the pore forming protein Gasdermin D, which formed mitochondrial pores and induced mitochondrial DNA (mtDNA) release into the cytosol of endothelial cells. mtDNA was recognized by the DNA sensor cGAS and generated the second messenger cGAMP, which suppressed endothelial cell proliferation by downregulating YAP1 signaling. This indicated that the surviving endothelial cells in the penumbrium of the inflammatory injury were compromised in their regenerative capacity. In an experimental model of inflammatory lung injury, deletion of cGas in mice restored endothelial regeneration. The results suggest that targeting the endothelial Gasdermin D activated cGAS-YAP signaling pathway could serve as a potential strategy for restoring endothelial function following inflammatory injury.

Background Colorectal cancer is among the most prominent malignant tumors endangering human health, with affected populations exhibiting an increasingly younger trend. The Kirsten ras (KRAS) gene acts as a crucial regulator in this disease and influences multiple signaling pathways. In the present study, the KRAS gene mutation-induced alteration of intestinal flora in colorectal cancer patients was explored, and the intestinal microbes that may be affected by the KRAS gene were examined to provide new insights into the diagnosis and treatment of colorectal cancer. Methods Deoxyribonucleic acid (DNA) was extracted from 177 colorectal cancer patients in our hospital. The mutation of the KRAS gene was subsequently detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), and survival analysis was performed. Moreover, genomic DNA was extracted from the fecal microbes in 30 of these patients, and the differences in the intestinal flora between mutation and non-mutation groups were evaluated using linear discriminant analysis (LDA) Effect size (LEfSe) analysis. Results KRAS gene mutation substantially affected the distant metastasis of colorectal cancer, and the survival prognosis in the non-mutation group was significantly superior compared to the mutation group. The mutation group had a notably higher prevalence of microbes including Roseburia, Parabacteroides, Metascardovia, Staphylococcus, Staphylococcaceae, and Bacillales than the non-mutation group. The presence of microbes in the non-mutation group, such as Clostridiales, Bacteroidetes, Lachnospiraceae, Coprococcus, and Ruminococcaceae was markedly higher than in the mutation group. Firmicutes were negatively correlated with the presence of Actinomyces and Bacteroidetes, while Bacteroidetes were positively associated with the level of Actinomyces. Conclusions In colorectal cancer, KRAS gene mutation can remarkably affect the survival prognosis and change the composition and abundance of intestinal flora, such as Roseburia, Parabacteroides, Metascardovia, Staphylococcus, and Bacillales, thereby influencing tumor development.

Objective— Transient receptor potential melastatin-2 (TRPM2) channel is a nonselective cation channel that mediates influx of Ca 2+ and Na + with relative permeability of P Ca: P Na ≈0.6 in response to cellular oxidative stress. As angiogenesis and ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possible role of vascular endothelial growth factor (VEGF)–induced reactive oxygen species production in activating TRPM2-dependent Ca 2+ signaling and in the mechanism of angiogenesis and ischemic neovascularization. Approach and Results— We observed that VEGF stimulation rapidly induced the association of TRPM2 and cellular Src kinase with vascular endothelial-cadherin forming a signalplex at vascular endothelial-cadherin junctions in endothelial cells. Using endothelial cells isolated from TRPM2 −/− mice or after small interfering RNA depletion of TRPM2, we demonstrated that TRPM2-activated Ca 2+ signaling was required for cellular Src kinase–induced phosphorylation of vascular endothelial-cadherin at Y658 and Y731, the crucial sites involved in vascular endothelial-cadherin internalization in response to VEGF. VEGF-induced reactive oxygen species generation activated TRPM2-induced Ca 2+ entry, whereas the reactive oxygen species–insensitive TRPM2 mutant (C1008→A) showed impaired Ca 2+ entry. Endothelial cells depleted of TRPM2 also displayed significantly perturbed migratory phenotype and impaired activation of cellular Src in response to VEGF. TRPM2 −/− mice reconstituted with wild-type myeloid cells demonstrated aberrant angiogenesis and neovascularization in the hindlimb ischemia model as compared with wild-type mice. Conclusions— VEGF-induced angiogenesis and postischemic neovascularization in mice required reactive oxygen species generation in endothelial cells and resultant TRPM2 activation. Thus, our findings provide novel insight into the role of TRPM2 in mechanism of angiogenesis and ischemic neovascularization.

Knowledge and technology transferring between universities and industries had been an important research focus of innovation management. Bibliometric research on the university-industry knowledge transferring had always used patent collaboration and citation data as indicators. However, patent licensing data were more representative and could target the knowledge transferring directions. This paper had gone through the data of Chinese academic-industry patent licensing and focused on the variances in regional level and geographic distance. Using patent licensing document analyzing method, the academic-industry knowledge flowing patterns had been discovered. Results showed that localization effects had been existed in those Chinese regions and the engagement of knowledge transferring was severely unbalanced.

This paper had studied “3 + 1” National Innovation Demonstration Zones (NIDZ) in China, which located in Beijing, Wuhan, Shanghai and Anhui province. There were national level instructions for innovation demonstration zones. These 4 regions would benefit from the specific policy approved by the Chinese government and the whole nation depended on them to improve creative S & T level in the future from “Made in China” to “Created in China”. This paper had compared different aspects among these 4 innovation zones. The “1” Anhui Hefei-Wuhu-Bengbu area (HWB) would benefit from experience made by the “3” earlier innovation zones.

The characteristics of science and technology activities (STA) have important effect on the characteristics of the research of science and technology policy (STP). On this argument, we review the research on the characteristics of STA and the characteristics of the study of STP, discuss the characteristic of STP itself and the effect on the research of STP, therefore summarize the characteristics the research of STP should have. The characteristics of the current STA are as below: its effect is irreversible and of wide range as well as high speed ; it faces with the risk of technology and market; it has ethical anomie; it is interdisciplinary and cross level and domain; it has national mission, etc. These characteristics make the research of STP need the following characteristics: Timeliness and scientific; Tolerance and face up to failure; Normative values; Extend research subject; national demand oriented, etc.

Different regions had various kinds of academic resources and industries competitors. The knowledge and innovation output generated by researchers in academy had been transferred into industries through patent licensing. Using the patent licensing document analyzing method and the mapping technique, the academic-industry knowledge flowing patterns of different regions in China had been discovered and visualized in maps. The regional performance of academic-industry knowledge transfer was rather mixed and unbalanced. Based on the licensing performance data, this paper had also generated a 4 × 4 block matrix as evaluation tool and ranked 28 Chinese regions into 8 levels according to their academic licensing performance. Further suggestions and advice had been given for regions in different levels.

This paper had collected the patent licensing documents of all Chinese universities and made a comprehensive study on licensing performance. With a whole set of data from SIPO, the exact licensing frequency number and licensing propensity number of Chinese universities had been obtained for the first time. On average, 16.03 patents (6%) per university had been licensed out to the industry, which is much lower than expectations. The frequency of licensing, propensity of licensing, number of partners (licensees), number of patent stocks, local-transfer ratio and the distribution of licensing frequency in terms of university-firm distance had been obtained in details. Five hypotheses had been made to discover the variances in university licensing performance. With the ANOVA technique, five hypotheses had been confirmed within the dataset, which had revealed a significant effect of patent stocks, local economic performance, central government support, existence of TTO and local government administration on university licensing performance.

Acidification of macrophage phagosomes serves an important bactericidal function. We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification. Measurement of the TRPM2 current in phagosomes identified TRPM2 as a functional redox-sensitive cation channel localized in the phagosomal membrane. Simultaneous measurements of phagosomal Ca2+ changes and phagosome acidification in macrophages undergoing phagocytosis demonstrated that TRPM2 was required to mediate the efflux of cations and for phagosomal acidification during the process of phagosome maturation. Acidification in phagosomes was significantly reduced in macrophages isolated from Trpm2-/- mice as compared to wild type, and acidification was coupled to reduced bacterial clearance in Trpm2-/- mice. Trpm2+/+ macrophages treated with the vacuolar H+-ATPase inhibitor bafilomycin showed reduced bacterial clearance, similar to that in Trpm2-/- macrophages. Direct activation of TRPM2 using adenosine diphosphate ribose (ADPR) induced both phagosomal acidification and bacterial killing. These data collectively demonstrate that TRPM2 regulates phagosomal acidification, and is essential for the bacterial killing function of macrophages.

Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition. The oxidant sensing-induced termination of neutrophil migration at the site of infection permits a smooth transition to the subsequent microbial killing phase.

Recovery of endothelial integrity after vascular injury is vital for endothelial barrier function and vascular homeostasis. However, little is known about the molecular mechanisms of endothelial barrier repair following injury. To investigate the functional role of forkhead box M1 (FoxM1) in the mechanism of endothelial repair, we generated endothelial cell-restricted FoxM1-deficient mice (FoxM1 CKO mice). These mutant mice were viable and exhibited no overt phenotype. However, in response to the inflammatory mediator LPS, FoxM1 CKO mice displayed significantly protracted increase in lung vascular permeability and markedly increased mortality. Following LPS-induced vascular injury, FoxM1 CKO lungs demonstrated impaired cell proliferation in association with sustained expression of p27(Kip1) and decreased expression of cyclin B1 and Cdc25C. Endothelial cells isolated from FoxM1 CKO lungs failed to proliferate, and siRNA-mediated suppression of FoxM1 expression in human endothelial cells resulted in defective cell cycle progression. Deletion of FoxM1 in endothelial cells induced decreased expression of cyclins, Cdc2, and Cdc25C, increased p27(Kip1) expression, and decreased Cdk activities. Thus, FoxM1 plays a critical role in the mechanism of the restoration of endothelial barrier function following vascular injury. These data suggest that impairment in FoxM1 activation may be an important determinant of the persistent vascular barrier leakiness and edema formation associated with inflammatory diseases.

Endothelial cells exhibit regulated exocytosis in response to inflammatory mediators such as thrombin and histamine. The exocytosis of Weibel-Palade bodies (WPBs) containing von Willebrand factor, P-selectin, and interleukin-8 within minutes after stimulation is important for vascular homeostasis. SNARE proteins are key components of the exocytic machinery in neurons and some secretory cells, but their role in regulating exocytosis in endothelial cells is not well understood. We examined the function of SNARE proteins in mediating exocytosis of WPBs in endothelial cells. We identified the presence of syntaxin 4, syntaxin 3, and the high affinity syntaxin 4-regulatory protein Munc18c in human lung microvascular endothelial cells. Small interfering RNA-induced knockdown of syntaxin 4 (but not of syntaxin 3) inhibited exocytosis of WPBs as detected by the reduction in thrombin-induced cell surface P-selectin expression. Thrombin ligation of protease-activated receptor-1 activated the phosphorylation of syntaxin 4 and Munc18c, which, in turn, disrupted the interaction between syntaxin 4 and Munc18. Protein kinase Cα activation was required for the phosphorylation of syntaxin 4 and Munc18c as well as the cell surface expression of P-selectin. We also observed that syntaxin 4 knockdown inhibited the adhesion of neutrophils to thrombin-activated endothelial cells, demonstrating the functional role of syntaxin 4 in promoting endothelial adhesivity. Thus, protease-activated receptor-1-induced protein kinase Cα activation and phosphorylation of syntaxin 4 and Munc18c are required for the cell surface expression of P-selectin and the consequent binding of neutrophils to endothelial cells.

The in vivo contributions of CD18 integrin-dependent and -independent mechanisms in mediating the increases in lung neutrophil (polymorphonuclear leukocyte; PMN) sequestration and microvascular permeability are not well understood. We determined the time course of these responses to Gram-negative sepsis in the mouse lung and addressed the specific contributions of CD18 integrins and ICAM-1. PMN sequestration in the lung was assessed by morphometric analysis, and transalveolar PMN migration was assessed by bronchoalveolar lavage. Lung tissue PMN number increased by 6-fold within 1 h after i.p. Escherichia coli challenge; this value peaked at 3 h (7-fold above control) and decreased at 12 h (3.5-fold above control). PMN migration into the airspace was delayed; the value peaked at 6 h and remained elevated up to 12 h. Saturating concentrations of anti-CD18 and anti-ICAM-1 mAbs reduced lung tissue PMN sequestration and migration; however, peak responses at 3 and 6 h were inhibited by 40%, indicating that only a small component of PMN sequestration and migration was CD18 dependent at these times. In contrast to the time-dependent decreased role of CD18 integrins in mediating PMN sequestration and migration, CD18 and ICAM-1 blockade prevented the increase in lung microvascular permeability and edema formation at all times after E. coli challenge. Thus, Gram-negative sepsis engages CD18/ICAM-1-independent mechanisms capable of the time-dependent amplification of lung PMN sequestration and migration. The increased pulmonary microvascular permeability induced by E. coli is solely the result of engagement of CD18 integrins even when PMN accumulation and migration responses are significantly CD18 independent.

We determined the role of vascular endothelial (VE)-cadherin complex in regulating the permeability of pulmonary microvessels. Studies were made in mouse lungs perfused with albumin-Krebs containing EDTA, a Ca2+ chelator, added to study the VE-cadherin junctional disassembly. We then repleted the perfusate with Ca2+ to restore VE-cadherin integrity. Confocal microscopy showed a disappearance of VE-cadherin immunostaining in a time- and dose-dependent manner after Ca2+ chelation and reassembly of the VE-cadherin complex within 5 min after Ca2+ repletion. We determined the125I-labeled albumin permeability-surface area product and capillary filtration coefficient ( K fc) to quantify alterations in the pulmonary microvessel barrier. The addition of EDTA increased 125I-albumin permeability-surface area product and K fc in a concentration-dependent manner within 5 min. The permeability response was reversed within 5 min after repletion of Ca2+. An anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion augmented the increase in K fc induced by Ca2+chelation and prevented reversal of the response. We conclude that the disassembled VE-cadherins in endothelial cells are mobilized at the junctional plasmalemmal membrane such that VE-cadherins can rapidly form adhesive contact and restore microvessel permeability by reannealing the adherens junctions.

IQGAP1 is a scaffold protein that associates with the endothelial adherens junction (AJs) protein beta-catenin and with the active form of monomeric GTPase Cdc42 to play an important role in mainta...

Objective— The goal of this study was to determine whether tumor necrosis factor α (TNFα)–induced Src activation and intercellular adhesion molecule-1 (ICAM-1) phosphorylation rapidly increase endothelial cell adhesivity and polymorphonuclear leukocyte (PMN) sequestration independently of de novo ICAM-1 synthesis. Methods and Results— TNFα exposure of mouse lungs for 5 minutes produced a 3-fold increase in 125 I-anti-ICAM-1 monoclonal antibody (mAb) binding and 111 In oxine-labeled PMN sequestration, as well as Src activation, ICAM-1 Tyr518 phosphorylation, and phospho- Tyr518-ICAM-1 coimmunoprecipitation with actin. The response was absent in Nox2 −/− lungs or following Src inhibition. In COS-7 cells transfected with wild-type (WT), phospho-defective (Tyr518Phe), or phospho-mimicking (Tyr518Asp) mouse ICAM-1 cDNA constructs, TNFα increased the B max of YN1/1.7.4 anti-ICAM-1 mAb binding to WT-ICAM-1 but not to Tyr518Phe-ICAM-1, indicating increased binding avidity secondary to ICAM-1 phosphorylation. This effect was mimicked by expression of the Tyr518Asp-ICAM-1 mutant. TNFα also increased the staining intensity and cell surface clustering of YN1/1.7.4 mAb-labeled WT-ICAM-1 that colocalized with F-actin, which was not observed with Tyr518Phe-ICAM-1 but was recapitulated with Tyr518Asp-ICAM-1. Finally, overexpression of ICAM-1 in mouse lungs significantly increased lipopolysaccharide-induced transvascular albumin leakage and bronchoalveolar lavage PMN counts at 2 and 24 hours after lipopolysaccharide inhalation compared with lungs expressing the Tyr518Phe ICAM-1 mutant. Conclusion— Src-dependent phosphorylation of endothelial cell ICAM-1 Tyr518 induces PMN adhesion by promoting ICAM-1 clustering, which we propose mediates rapid-phase lung vascular accumulation of PMNs during inflammation.