Antenna Array Design Based on Low-Temperature Co-Fired Ceramics.

With the continuous development of wireless communication technology, the frequency band of 6G communication systems is moving towards higher frequencies such as millimeter waves and terahertz. In such high-frequency situations, wireless transmission requires antenna modules to be provided with characteristics of miniaturization, high integration, and high gain, which presents new challenges to the development of antenna technology. In this article, a 4 × 4 antenna array using multilayered low-temperature co-fired ceramic is proposed, operating in W-band, with a feeding network based on substrate-integrated waveguide, and an antenna element formed through the combination of a substrate-integrated cavity and surface parasitic patches, which guaranteed the array to possess the advantages of high integration and high gain. Combined with the substrate-integrated waveguide to a rectangular waveguide transition structure designed in the early stage, a physical array with a standard metal rectangular waveguide interface was fabricated and tested. The test results show that the gain of the antenna array is higher than 18 dBi from 88 to 98 GHz, with a maximum of 20.4 dBi.

Applications of nanomaterials in anti-VEGF treatment for ophthalmic diseases.

Angiogenesis has been determined to be essential in the occurrence and metastasis of diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), choroidal neovascularization (CNV), retinopathy of prematurity (ROP), tumor, etc. However, the clinical use of anti-vascular endothelial growth factors (VEGF) drugs is currently limited due to its high cost, potential side effects, and need for repeated injections. In recent years, nanotechnology has shown promising results in inhibiting neovascularization and reducing reactive oxygen species (ROS) or inflammatory factors. Some nanomaterials can also act as vehicles for drug delivery, such as lipid nanoparticles and PLGA. The process of angiogenesis and its molecular mechanism are discussed in this article. At the same time, this study aims to systematically review the research progress of nanotechnology and offer more treatment options for neovascularization-related diseases in clinical ophthalmology.

A new ultra-wide-field fundus dataset to diabetic retinopathy grading using hybrid preprocessing methods.

Diabetic retinopathy(DR) is a common early diabetic complication and one of the main causes of blindness. In clinical diagnosis and treatment, regular screening with fundus imaging is an effective way to prevent the development of DR. However, the regular fundus images used in most DR screening work have a small imaging range, narrow field of vision, and can not contain more complete lesion information, which leads to less ideal automatic DR grading results. In order to improve the accuracy of DR grading, we establish a dataset containing 101 ultra-wide-field(UWF) DR fundus images and propose a deep learning(DL) automatic classification method based on a new preprocessing method. The emerging UWF fundus images have the advantages of a large imaging range and wide field of vision and contain more information about the lesions. In data preprocessing, we design a data denoising method for UWF images and use data enhancement methods to improve their contrast and brightness to improve the classification effect. In order to verify the efficiency of our dataset and the effectiveness of our preprocessing method, we design a series of experiments including a variety of DL classification models. The experimental results show that we can achieve high classification accuracy by using only the backbone model. The most basic ResNet50 model reaches an average of classification accuracy(ACA) 0.66, Macro F1 0.6559, and Kappa 0.58. The best-performing Swin-S model reaches ACA 0.72, Macro F1 0.7018, and Kappa 0.65. DR grading using UWF images can achieve higher accuracy and efficiency, which has practical significance and value in clinical applications.

HO-1 protects the nerves of rats with cerebral hemorrhage by regulating the PI3K/AKT signaling pathway.

Objective: This study aimed to investigate the neuroprotective effect of heme oxygenase-1 (HO-1) on the PI3K/AKT signaling pathway in rats with cerebral hemorrhage. Materials and methods: Adult male Sprague-Dawley rats were randomly divided into: a sham group, a model group and an HO-1 inhibitor group (ZnPP group). Functional defects after surgery were scored according to the Longa5 standard. Hemotoxylin and eosin staining was used to detect whether the model was constructed successfully. Superoxide dismutase (SOD) vitality and malondialdehyde (MDA) content were calculated by the xanthine oxidase method and thiobarbituric acid method, respectively. Blood-brain barrier permeability was measured by Evans Blue. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The expression of Bcl-2 and BAX was evaluated by immunohistochemistry and the expression of PI3K, p-PI3K, AKT and p-AKT was tested by Western blotting. Results: The rat intracerebral hemorrhage model was successfully constructed. Compared with the model group, the bleeding in the ZnPP group was more serious, the cell edema and deformation were aggravated, and the neurological deficit score in the rat was significantly increased. In addition, the content of Evans blue, MDA, the number of apoptotic cells, the water content of brain tissue and the expression of BAX were significantly increased, while the SOD activity and the expressions of Bcl-2, p-PI3K and p-AKT protein were decreased. Conclusion: HO-1 could protect the nerves of rats with cerebral hemorrhage by regulating the PI3K/AKT signaling pathway.

Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats via Extracellular Signal-Regulated Kinase/Cyclic Adenosine Monophosphate Response Element Binding Protein Signaling Pathway.

OBJECTIVE: To investigate the mechanism of dexmedetomidine (Dex) in improving brain damage induced by cerebral ischemia-reperfusion injury in rats. METHODS: Rats were randomly divided into a sham operation group, ischemia-reperfusion group, Dex group, piracetam group, and yohimbine + Dex group, with 12 rats per group. 2,3,5-Triphenyltetrazolium chloride staining was used to analyze cerebral infarct size. Hematoxylin-eosin staining and immunohistochemistry were used to observe brain damage caused by ischemia-reperfusion. Cognitive and memory functions was detected by Morris water maze test, and the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (CREB) were measured by Western blot. RESULTS: Cognitive dysfunction was improved in the Dex group and the piracetam group compared with the ischemia-reperfusion group. Compared with the ischemia-reperfusion group, infarct size and neuronal cell death rates were decreased in the Dex group and the piracetam group. The expression of phosphorylated ERK1/2 and phosphorylated CREB in the Dex group was increased, whereas the expression of phosphorylated ERK1/2 and phosphorylated CREB in the yohimbine + Dex group was lower than in the Dex group (P < 0.05). CONCLUSIONS: Dex improved ischemic brain damage by promoting signal transduction of the ERK/CREB pathway, which may provide new ways for clinical treatment of cerebral ischemia-reperfusion injury.

Down-Regulation of Mir-145 Improves Learning and Memory Abilities in Epileptic Rats by Regulating Hippocampal Neuron Apoptosis.

OBJECTIVES: To investigate effect of miR-145 on learning and memory ability in rats with epilepsy. METHODS: Rats with epilepsy were induced by lithium chloride-pilocarpine. miR-145 antagomir and antagomir-control were injected into epileptic brains by the stereotactic technique, respectively. Then, rats were divided into a normal group (N), epilepsy group (Ep), miR-145 antagomir group (A) and antagomir-control group (C). After 1 and 7 days of treatment, the expression of miR-145 and Caspase-9 were detected, and the apoptosis of hippocampal neurons in CA1 of hippocampus was detected. After 7 days of treatment, the learning and memory abilities of rats was measured by using the Morris water maze test. RESULTS: The rat epilepsy model was successfully constructed. Compared with the N group, the target quadrant time and platform crossing times were reduced and the expression of miR-145 and Caspase-9 was increased in the epilepsy groups (P < 0.05). Compared with the Ep and C groups, the target quadrant time and platform crossing times were increased and the expression of miR-145 and Caspase-9 was down-regulated in the A group (P < 0.05). The number of apoptotic hippocampal neurons in the hippocampal CAl area of the Ep group was more than that in the N group and in the A group was less than that in the C group at 1 and 7 days after modeling respectively (P < 0.05). CONCLUSIONS: Down-regulated miR-145 improved the apoptosis of hippocampal neurons by reducing the Caspase-9 expression in hippocampus and further affected learning and memory abilities of rats with epilepsy.

Effects of a new anatomical adaptive titanium mesh cage on supportive load at the cervical endplate: a morphological and biomechanical study / 南方医科大学学报

OBJECTIVE@#To assess the geometrical matching of a new anatomical adaptive titanium mesh cage (AA-TMC) with the endplate and its effect on cervical segmental alignment reconstruction in single- and two-level anterior cervical corpectomy and fusion (ACCF) and compare the compressive load at the endplate between the AA-TMC and the conventional titanium mesh cage (TMC).@*METHODS@#Twelve cervical cadaveric specimens were used to perform single- and two-level ACCF. The interbody angle (IBA), interbody height (IBH) and the interval between the AA-TMC and the endplate were evaluated by comparison of the pre- and postoperative X-ray images. The maximum load at the endplate was compared between the AA-TMC and TMC based on American Society for Testing and Materials (ASTM) F2267 standard.@*RESULTS@#No significant differences were found between the preoperative and postoperative IBA and IBH in either single-level ACCF (11.62°±2.67° 12.13°±0.69° and 23.90±2.18 mm 24.23±1.13 mm, respectively; > 0.05) or two-level ACCF (15.63°±5.06° 16.16°±1.05°and 42.93±3.51 mm 43.04±1.70 mm, respectively; > 0.05). The mean interval between the AA-TMC and the endplate was 0.37 ± 0.3 mm. Compared to the conventional TMC, the use of AA-TMC significantly increased the maximum load at the endplate in both single-level ACCF (719.7±5.5 N 875.8±5.2 N, < 0.05) and two-level ACCF (634.3±5.9 N 873±6.1 N, < 0.05).@*CONCLUSIONS@#The use of AA-TMC in single-level and two-level ACCF can significantly increase the maximum load at the endplate to lower the possibility of implant subsidence and allows effective reconstruction of the cervical alignment.

Comparison of the effect of navigation template assisted spinal pedicle fixation and traditional pedicle screw fixation:a Meta-analysis / 中国骨伤

OBJECTIVE@#To systematically evaluate the efficacy of rapid prototyping drill navigation template-assisted pedicle screw fixation and traditional anatomic landmark-based fixation in the treatment of spinal disease by accessing and searching some relevant literatures home and abroad.@*METHODS@#Randomized Controlled Trials (RCTs) and prospective case-control studies or retrospective case-control studies about rapid prototyping drill templates-assisted pedicle screw fixation and traditional anatomic landmark-based fixation for the treatment of spinal disease were searched electronically in PubMed, The Cochrane Library(Issue 5, 2017), Clinical Trial, Google Scholar, Web of Science, CNKI, Wanfang database and VIP database before June 2017. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, and extracted the data. The methodological quality of randomized controlled trials were evaluated by the Cochrane Handbook, and prospective case-control studies and retrospective case-control studies were evaluated by the NOS scale. The outcomes were analyzed using RevMan 5.3 software provided by the Cochrane information management system.@*RESULTS@#A total of 7 articles were included, including 2 RCTs, 1 prospective case-control study and 4 retrospective case-control studies. A total of 237 patients were implanted with 1 688 pedicle screws, including 898 screws in the navigation template group, 790 screws in the conventional method group. Meta-analysis results showed that there was significant difference in the excellent rate of screw implantation between navigation template group and conventional method group [OR=5.05, 95% CI(3.13, 8.16), <0.000 01], there was significant difference in operative time, intraoperative blood loss for thoracolumbar surgery [WMD=-27.19, 95% CI(-38.21, -16.17), <0.000 01; WMD=-100.82, 95% CI(-182.26, -19.37), =0.02].@*CONCLUSIONS@#Compared with traditional pedicle screw fixation, navigation template spine pedicle screw fixation has better clinical effect, which can improve the excellent rate of screw placement, reduce the operation time and intraoperative bleeding.

Rapid prototyping navigation template assisted cervical screw implantation:a review / 中国骨伤

The cervical screw fixation has been used widely in the clinic setting due to the high fusion rate, immediate fixation of the surgical segment and good correction of the deformity. However, owing to the variation of anatomical structures and the narrow pedicle screws, it's rather difficult to implant the screws through traditional methods. The perforation rate of the screw is high, which can cause serious complications such as neurovascular injury. In recent years, rapid prototyping navigation templates have been reported in the appilication to assist cervical screw placement for improving the accuracy of screw placement. In this paper, we reviewed and summarized published literatures about navigation template assisted cervical screw implantation in the past 20 years, systematically introduced the methods of producing and using of navigation templates, the development of design concept and the status of application in cervical spine surgery. To date, relevant clinical and cadaveric studies confirm that the use of rapid prototyping navigation template assisted cervical screw placement in cervical surgery can reduce screw perforation rate, intraoperative ionizing radiation injury and operation time, which is worth applying in the clinical practice. However, specific clinical effects of different design types of navigation templates are not well summarized. As a result, more clinical and cadaveric studies comparing the accuracy and safety of navigation templates of different design types are needed to help clinicians select the appropriate navigation template for surgery.

Eestablishment of the model of goat lumbar spinal fusion by 3D printing technology and experimental perioperative management / 中国骨伤

<p><b>OBJECTIVE</b>To explore the feasibility and the attention of perioperative management of goat lumbar fusion model for individualized 3D printing technology.</p><p><b>METHODS</b>According to preoperative X-ray and CT three dimensional reconstruction data of 10 males Boer goat's lumbar(1-2 years old, weight 35-45 kg), the preoperative open height were determined, meanwhile, according to the theoretical entry point of nails, the length of steel plate, arc, and setting position, screw length for reference were determined, the lumbar lateral anterior plate was designed and 3D-printed. Goats lied on the right side, under the general anesthesia, the lumbar vertebrae of the goats and the adjacent intervertebral disc were resected, and the titanium cage after the bone graft was implanted into the goat, the 3D-print lateral bone plate was fixed. After operation, feeding, fluid infusion, anti infection, postoperative complications management, respiratory digestion perioperative management were performed.</p><p><b>RESULTS</b>The 10 models for goats were successful in results. Postoperative X-ray film and three-dimensional reconstruction of CT showed that titanium cage and bone plate were in good position and reliable. Three months after the operation, CT 3D reconstruction and micro-CT of the goat were observed, and the fusion of the spine was observed. Imaging studies showed that the fusion of the lateral bone plate fixation titanium cage was both at the end of the titanium cage and the dense bone trabecular formation between the vertebral bodies.</p><p><b>CONCLUSIONS</b>The 3D printing technology sets up the goat lumbar spinal fusion model successfully, which is a kind of effective, more successful, reliable and stable method, perioperative management. The method is scientific, practical, and more humanized, to ensure that lumbar lateral successfully implanted the nail plate of lateralanterior internal fixation system, with reduction of occurrence of surgical complications.</p>

Impact of anterior cervical fusion surgeries on adjacent segments: a finite element analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in the range of motion (ROM) and stress of the intervertebral disc and facet joint of the adjacent segments following anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) using finite element analysis.</p><p><b>METHODS</b>A three-dimensional finite element model of the lower cervical vertebrae was constructed and validated by comparing the ROM of the finite element model against the published data. After the validation of successful modeling, finite element models of ACDF and ACCF were constructed. The ROM and the stress of the intervertebral disc and facet joint of the adjacent segments were compared between the intact lower cervical vertebrae and the cervical vertebrae after ACDF and ACCF.</p><p><b>RESULTS</b>The ROM of the finite element model was consistent with the published data. The total ROM and the ROM of the fusion segments with ACDF and ACCF were significantly decreased compared with the intact cervical vertebrae. In the adjacent segments following ACDF and ACCF, the ROM the adjacent segments and the stress peak of the intervertebral disc and facet joint all increased obviously compared with those of intact cervical vertebrae.</p><p><b>CONCLUSION</b>After fusion surgeries, the total ROM of the cervical vertebrae decreases and the ROM of the adjacent segment increases. The stress peak of the intervertebral disc and facet joint of the adjacent segments also increases to significantly alter the physiological characteristics of the intact cervical vertebrae.</p>

Copolymers Based on 1,3-Bis(carbazol-9-yl)benzene and Three 3,4-Ethylenedioxythiophene Derivatives as Potential Anodically Coloring Copolymers in High-Contrast Electrochromic Devices.

In this study, copolymers based on 1,3-bis(carbazol-9-yl)benzene (BCz) and three 3,4-ethylenedioxythiophene derivatives (3,4-ethylenedioxythiophene (EDOT), 3,4-(2,2-dimethylpropylenedioxy)thiophene (ProDOT-Me2), and 3,4-ethylenedithiathiophene (EDTT)) were electrochemically synthesized and their electrochemical and electrochromic properties were characterized. The anodic copolymer P(BCz-co-ProDOT) with BCz/ProDOT-Me2 = 1/1 feed molar ratio showed high optical contrast (ΔT%) and coloring efficiency (η), measured as 52.5% and 153.5 cm²âˆ™C-1 at 748 nm, respectively. Electrochromic devices (ECDs) based on P(BCz-co-EDOT), P(BCz-co-ProDOT), and P(BCz-co-EDTT) as anodic polymer layers, and poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) (PEDOT-PSS) as cathodic polymer layer were fabricated. P(BCz-co-ProDOT)/triple-layer PEDOT-PSS ECD showed three different colors (light yellow, yellowish-blue, and dark blue) at different applied potentials. In addition, the highest optical contrast (ΔT%) of P(BCz-co-ProDOT)/triple-layer PEDOT-PSS ECD was found to be 41% at 642 nm and the coloration efficiency was calculated to be 416.5 cm²âˆ™C-1 at 642 nm. All ECDs showed satisfactory optical memories and electrochemical cyclic stability.

Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.</p><p><b>METHODS</b>CLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells.</p><p><b>RESULTS</b>Quantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml.</p><p><b>CONCLUSIONS</b>The C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.</p>

Requirement for Foxd3 in the maintenance of neural crest progenitors.

Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3(flox/-); Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

Neural crest stem cells.

Stem cells are defined by their ability to both self-renew and give rise to multiple lineages in vivo and/or in vitro. As discussed in other chapters in this volume, the embryonic neural crest is a multipotent tissue that gives rise to a plethora of differentiated cell types in the adult organism and is unique to vertebrate embryos. From the point of view of stem cell biology, the neural crest is an ideal source for multipotent adult stem cells. Significant advances have been made in the past few years isolating neural crest stem cell lines that can be maintained in vitro and can give rise to many neural crest derivatives either in vitro or when placed back into the context of an embryo. The initial work identifying these stem cells was carried out with premigratory neural crest from the embryonic neural tube. Later, neural crest stem cells were isolated from postmigratory neural crest, presumably more restricted in developmental potential. More recently it has been demonstrated that neural crest stem cell progenitors persist in the adult in at least two differentiated tissues, the enteric nervous system of the gut and the whisker follicles of the facial skin. In all cases, the properties of the stem cells derived reflect their tissue of origin and the potential of the progenitors becomes more restricted with age. In this chapter we will review this work and speculate on future possibilities with respect to combining our knowledge of neural crest gene function in the embryo and the manipulation of adult neural crest stem cells in vitro and eventually in vivo.

Expression and shifting subcellular localization of the transcription factor, Foxd3, in embryonic and adult pancreas.

Multipotent progenitor cells self renew throughout an animal's lifetime and can differentiate to give rise to different cell types. Before we can fully understand the developmental potential of progenitor cells and control their differentiation both in vivo and in vitro as stem cells, identification and characterization of the genes that control stem cell fate must first be obtained. Foxd3, a member of the forkhead family of transcriptional regulators, is required for the maintenance of embryonic stem cells and trophoblast stem cells of the early mouse embryo. We describe here the expression of this protein in the developing pancreas. Foxd3 is expressed in most beta cells and infrequently in alpha and PP cells but is not expressed in somatostatin cells. The subcellular localization of Foxd3 varies with fat content in the diet; with a high fat diet the protein is found primarily in the cytoplasm while a low fat diet results in nuclear localization. Foxd3 is differentially localized in a rat model of diabetes: it is nuclear in ZDF rats but cytoplasmic in their lean counterparts. Foxd3 is nuclear in Lep(Ob/Ob) mice.

[Establishing mouse embryonic stem cell line carrying a fluorescent undifferentiated marker].

To label mouse ES cells,a cell line derived from the inner cell mass of 3.5-day blastocysts,with enhanced green fluorescent protein (EGFP), the vector of pRex-1-EGFP was transferred into mouse ES cells by electroporation. The expressions of Rex-1 in undifferentiated and differentiated ES cells were detected by the microscopic observation of EGFP and by RT-PCR. The results showed that the EGFP gene was transferred into the mouse ES cell line, and the transfected cells in undifferentiated state showed high levels of EGFP expression. When the cells began to differentiate, the EGFP expressions were gradually reduced. A mouse ES cell line expressing EGFP under the control of Rex-1 gene promoter was generated. The cell line provides a powerful approach for the research of the process of mammalian development and for the screening of small molecules that can regulate this process.

The use of knockout mouse technology to achieve tissue selective expression of angiotensin converting enzyme.

The resin angiotensin system (RAS) plays an essential role in blood pressure regulation and electrolyte homeostasis. The effecter peptide of the RAS, angiotensin II, is produced by angiotensin converting enzyme (ACE) in multiple tissues. Genetic deletion of ACE in mice resulted a phenotype of low blood pressure, anemia and kidney defects. However, it is not clear whether the lack of the systemic or the local production of angiotensin II caused these defects. To understand the role of local angiotensin II production, we developed a method to achieve tissue specific ACE expression through homologous recombination. In this review, we discuss mouse models in which endothelial ACE was eliminated and replaced by hepatic ACE. These studies suggest that both circulating angiotensin II and local angiotensin II production play a role in angiotensin II generation; the elimination of local angiotensin II generation up-regulates systemic production and maintains physiologic homeostasis.

Circulating versus local angiotensin II in blood pressure control: lessons from tissue-specific expression of angiotensin-converting enzyme (ACE).

The renin angiotensin system (RAS) is a central player in blood pressure control. Its effector peptide, angiotensin II, regulates blood pressure through coordinated actions in multiple tissues. The RAS is generally considered to be an endocrine system, and angiotensin II to be a circulating hormone. In recent years, however, a role for locally produced angiotensin II has been proposed. The major site for angiotensin II production is endothelium, where angiotensin-converting enzyme (ACE) is abundantly expressed. To elucidate the relative importance of circulating angiotensin II versus locally produced angiotensin II, one approach is to create a mouse model in which ACE is expressed in a tissue-specific manner. In this review, we discuss strategies to create such a model. In a mouse model we generated using a novel promoter-swapping technique, the endothelial ACE is eliminated and replaced by ectopic production of ACE in the liver. This model specifically addresses the question of whether local production of angiotensin II is essential for RAS function.

Newly recognized physiologic and pathophysiologic actions of the angiotensin-converting enzyme.

Despite several decades of research into the renin-angiotensin system, new aspects of this endocrine system are elucidated every few years, expanding its role not only in hypertension but also in diabetes, oncology, and cardiology. In this review, we describe newly recognized physiologic actions of the angiotensin-converting enzyme (ACE). These include the role of local versus systemic ACE in maintaining blood pressure, the physiology of bradykinin accumulation during ACE inactivation, and the role of alternate "non-angiotensin" substrates and potential non-enzymatic properties of ACE.