Vacuolar H⁺-ATPase in Diabetes, Hypertension, and Atherosclerosis

Vacuolar H+-ATPase (V-ATPase) is a multisubunit protein complex which, along with its accessory proteins, resides in almost every eukaryotic cell. It acts as a proton pump and as such is responsible for regulating pH in lysosomes, endosomes, and the extracellular space. Moreover, V-ATPase has been implicated in receptor-mediated signaling. Although numerous studies have explored the role of V-ATPase in cancer, osteoporosis, and neurodegenerative diseases, research on its involvement in vascular disease remains limited. Vascular diseases pose significant challenges to human health. This review aimed to shed light on the role of V-ATPase in hypertension and atherosclerosis. Furthermore, given that vascular complications are major complications of diabetes, this review also discusses the pathways through which V-ATPase may contribute to such complications. Beginning with an overview of the structure and function of V-ATPase in hypertension, atherosclerosis, and diabetes, this review ends by exploring the pharmacological potential of targeting V-ATPase.</p

EnvGuard: Guaranteeing Environment-Centric Safety and Security Properties in Web of Things

Web of Things (WoT) technology facilitates the standardized integration of IoT devices ubiquitously deployed in daily environments, promoting diverse WoT applications to automatically sense and regulate the environment. In WoT environment, heterogeneous applications, user activities, and environment changes collectively influence device behaviors, posing risks of unexpected violations of safety and security properties. Existing work on violation identification primarily focuses on the analysis of automated applications, lacking consideration of the intricate interactions in the environment. Moreover, users' intention for violation resolving strategy is much less investigated. To address these limitations, we introduce EnvGuard, an environment-centric approach for property customizing, violation identification and resolution execution in WoT environment. We evaluated EnvGuard in two typical WoT environments. By conducting user studies and analyzing collected real-world environment data, we assess the performance of EnvGuard, and construct a dataset from the collected data to support environment-level violation identification. The results demonstrate the superiority of EnvGuard compared to previous state-of-the-art work, and confirm its usability, feasibility and runtime efficiency

Cloning of neuraminidase (NA) gene and identification of its antiviral activity

Neuraminidase not only works as an antigen, inducing target-specific antibodies, but also plays a role of  enzyme activity and destroys the sialic acid receptor required by virus infection of the host cell surface which  protects the host from virus damage. In order to explore a new idea to use neuraminidase (NA) gene and  produce disease-resistant transgenic poultry, prokaryotic expression vector pGEX-NA was constructed to  make NA polyclone antibody. Eukaryotic expression vector pcDNA3.0-NA and pcDNA3.0/EGFP-NA was  constructed to reveal its subcelluar location by immunofluorescence and enhanced green fluorescent fusion  protein (EGFP). Chicken embryonic fibroblast (CEF) cells were transfected with pcDNA3.0-NA and selected by  G418 for two weeks, the transfected cells were challenged by Newcastle disease virus (NDV), the morphology of CEF cells were observed to detect the antiviral ability of NA gene. CEF cells were incubated by the cell  lysates extracted from the NIH 3T3 cells, which were transfected with pcDNA3.0-NA. The results show that  pGEX-NA could express NA protein in vitro and NA polyclone antibody worked very well; immunofluorescence and EGFP fusion protein revealed that NA protein located at the cytoplasm near the membrane; NDV-CEF  inhibition experiment showed the NA protein could resist and delayed CEF cells from NDV infection.Key words: Neuraminidase (NA), newcastle disease virus (NDV), antiviral activity, chicken embryonic fibroblast (CEF)

Kirigami-inspired, highly stretchable micro-supercapacitor patches fabricated by laser conversion and cutting.

The recent developments in material sciences and rational structural designs have advanced the field of compliant and deformable electronics systems. However, many of these systems are limited in either overall stretchability or areal coverage of functional components. Here, we design a construct inspired by Kirigami for highly deformable micro-supercapacitor patches with high areal coverages of electrode and electrolyte materials. These patches can be fabricated in simple and efficient steps by laser-assisted graphitic conversion and cutting. Because the Kirigami cuts significantly increase structural compliance, segments in the patches can buckle, rotate, bend and twist to accommodate large overall deformations with only a small strain (&lt;3%) in active electrode areas. Electrochemical testing results have proved that electrical and electrochemical performances are preserved under large deformation, with less than 2% change in capacitance when the patch is elongated to 382.5% of its initial length. The high design flexibility can enable various types of electrical connections among an array of supercapacitors residing in one patch, by using different Kirigami designs

Revisiting the Brain Renin-Angiotensin SystemFocus on Novel Therapies

Purpose of Review Although an independent brain renin-angiotensin system is often assumed to exist, evidence for this concept is weak. Most importantly, renin is lacking in the brain, and both brain angiotensinogen and angiotensin (Ang) II levels are exceptionally low. In fact, brain Ang II levels may well represent uptake of circulating Ang II via Ang II type 1 (AT1) receptors. Recent Findings Nevertheless, novel drugs are now aimed at the brain RAS, i.e., aminopeptidase A inhibitors should block Ang III formation from Ang II, and hence diminish AT1 receptor stimulation by Ang III, while AT2 and Mas receptor agonists are reported to induce neuroprotection after stroke. The endogenous agonists of these receptors and their origin remain unknown. Summary This review addresses the questions whether independent angiotensin generation truly occurs in the brain, what its relationship with the kidney is, and how centrally acting RAS blockers/agonists might work

Targeting angiotensinogen with RNA-based therapeutics

PURPOSE OF REVIEW: To summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases. RECENT FINDINGS: Liver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease. SUMMARY: Targeting angiotensinogen with RNA-based therapeutics is a promising new tool to treat hypertension and diseases beyond. Their long-lasting effects are particularly exciting, and if translated to a clinical application of at most a few administrations per year, may help to eliminate nonadherence

A novel, simple near-infrared thoracoscopic technique by a particular route for locating lung nodules

BackgroundThe localization of pulmonary nodules prior to thoracoscopic surgery remains challenging for thoracic surgeons, especially for those nodules that are not visible or palpable on the lung surface. Our study is a simple and effective minimally invasive method using indocyanine green through a special pathway to locate pulmonary nodules and fluorescence thoracoscopic surgery.MethodsThoracoscopic surgery was performed for 18 undiagnosed peripheral non-solid nodules no larger than 2 cm after location. After 0.3 mg/kg indocyanine green was injected through the peripheral vein, the puncture needle was pulled out after it reached approximately 1 cm of the pulmonary parenchyma near the nodules. This was followed by transfer to the operating room. The nodule was initially localized by using a near-infrared thoracoscope to visualize indocyanine green fluorescence. Then, thoracoscopic resection was performed.ResultsEighteen patients received this special and simple localization method, and underwent near-infrared, image-guided, video-assisted thoracoscopic surgery resection. Median computed tomography (CT) tumor size was 1.2 cm. Median depth from the pleural surface is 1.6 cm (range, 0.1–4.6 cm). The median time of CT-guided intervention was 12 min. The duration of thoracoscopic surgery was 67 min. Indocyanine green fluorescence was clearly identified in 17 of 18 patients (94.4%). The surgical margins were all negative on final pathology. The final diagnoses included 17 primary lung cancers, and 1 benign lung tumor.ConclusionsCT-guided single puncture of indocyanine green after peripheral intravenous injection is a simple, effective, and safe method to locate the nodule. This offers surgeons the ease of localization through direct indocyanine green fluorescence imaging, and it can be used as an effective alternative to other placement methods of locating pulmonary nodules

Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics

Proliferative Activity and Neuroprotective Effect of Ligustrazene Derivative by Irritation of Vascular Endothelial Growth Factor Expression in Middle Cerebral Artery Occlusion Rats

Purpose: To investigate the proliferative activity and neuroprotective effect of a newly identified ligustrazine derivative (4-((3,5,6-trimethylpyrazine-2 yl)methoxyl)-3-methox-ybenzoic acid-3,5,6- trimethylpyrazin- 2-methyl ester, T VA) and the possible mechanism related to vascular endothelial growth factor (VEGF) in cerebral ischemic injury.Methods: The pharmacological activity of T-VA was evaluated using MTT ((3 (4,5-dimethylthiazolyl2- yl)-2,5-diphenyltetrazolium bromide)) assay, while cellular morphology was observed with hematoxylin and eosin (HE) staining. Chick chorioallantoic membrane (CAM) model, immuno-histochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of VEGF. Middle cerebral artery occlusion (MCAO) model was used to investigate both VEGF expression and the survival rate after treatment with T-VA.Results: T-VA promoted neuron activity, and the doses of 15 and 30 μM showed more significant effect (p &lt; 0.05). The viability of PC12 cells increased significantly in T-VA (30 and 60 μM) groups (p &lt; 0.05) and increased in a dose dependent manner. Immunohistochemical analysis showed stimulated VEGF expression, and CAM model results showed that T-VA (20 mg/egg) significantly promoted microangiogenesis (p &lt; 0.01). Moreover, in MCAO model, the survival rate of T-VA (60 mg/kg) group reached 86.7 % while for the ischemia group it was 60.0 %. In addition, ELISA results showed that T-VA promoted the expression of VEGF (p &lt; 0.05).Conclusion: These findings indicate that T-VA helps to prevent ischemic injury by increasing VEGF expression.Keywords: Ligustrazine, Neuron, PC12 cell, Chick Chorioallantoic Membrane, Middle Cerebral Artery Occlusion, Vascular Endothelial Growth Facto