Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling.

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for prostaglandin synthesis during inflammation and immune responses. Our previous results show that NAD+ level decreased in activated macrophages while nicotinamide mononucleotide (NMN) supplementation suppressed the inflammatory responses via restoring NAD+ level and downregulating COX-2. However, whether NMN downregulates COX-2 in mouse model of inflammation, and its underlying mechanism needs to be further explored. In the present study, we established LPS- and alum-induced inflammation model and demonstrated that NMN suppressed the inflammatory responses in vivo. Quantitative proteomics in mouse peritoneal macrophages identified that NMN activated AhR signaling pathway in activated macrophages. Furthermore, we revealed that NMN supplementation led to IDO1 activation and kynurenine accumulation, which caused AhR nuclear translocation and activation. On the other hand, AhR or IDO1 knockout abolished the effects of NMN on suppressing COX-2 expression and inflammatory responses in macrophages. In summary, our results demonstrated that NMN suppresses inflammatory responses by activating IDO-kynurenine-AhR pathway, and suggested that administration of NMN in early-stage immuno-activation may cause an adverse health effect.

Designing flower-like MOFs-derived N-doped carbon nanotubes encapsulated magnetic NiCo composites with multi-heterointerfaces for efficient electromagnetic wave absorption.

In order to acquire exceptional electromagnetic wave absorption properties, the microstructure design and component modification of composites are essential. Metal-organic frameworks (MOFs), due to the unique metal-organic crystalline coordination, tunable morphology, high surface area, and well-defined pores, have been regarded as promising electromagnetic wave absorption materials precursors. However, the inadequate contact abilities between adjacent MOFs nanoparticles endow it with undesirable electromagnetic wave dissipation capacity at a low filler loading, which is a great challenge to break size effect of nanoparticles to achieve efficient absorption. Herein, NiCo-MOFs derived N-doped carbon nanotubes encapsulated with NiCo nanoparticles anchored on flowers-like composites (denoted as NCNT/NiCo/C) were successfully prepared through facile hydrothermal method followed by thermal chemical vapor deposition with melamine-assisted catalyst. By controlling the Ni/Co ratio in precursor, the tunable morphology and microstructure of MOFs are achieved. Most importantly, the derived N-doped carbon nanotubes tightly connect the adjacent nanosheets to construct the special 3D interconnected conductive network, which effectively accelerates the charge transfer and improves the conduction loss. And notably, the NCNT/NiCo/C composite delivers excellent electromagnetic wave absorption performance with minimum reflection loss of -66.1 dB and wide effective absorption bandwidth up to 4.64 GHz when the Ni/Co ratio is 1:1. This work provides a novel method for the preparation of morphology controllable MOFs-derived composites and realizes high-performance electromagnetic wave absorption properties.

Characteristics of Migration Among HIV-Positive MSM - Guangxi Zhuang Autonomous Region, China, 2005-2021.

What is already known about this topic?: Migration has a significant impact on the transmission of human immunodeficiency virus (HIV). To date, there have been few studies examining the characteristics of migration among HIV-positive men who have sex with men (MSM). What is added by this report?: The prevalence of migrants among newly reported HIV-positive MSM in Guangxi Zhuang Autonomous Region increased from 2005 to 2021. Yulin Prefecture had the highest proportion of out-migrant MSM (12.6%), while Nanning Prefecture had the highest proportion of in-migrant MSM (55.9%). Risk factors associated with migration among MSM included being in the 18-24 age range, having a college education or higher, and being a student. What are the implications for public health practice?: A complex prefecture-level network of HIV-positive MSM exists in Guangxi. To ensure effective follow-up management and antiretroviral therapy for migrant MSM, effective measures must be taken.

Global 1 km × 1 km gridded revised real gross domestic product and electricity consumption during 1992-2019 based on calibrated nighttime light data.

As fundamental data, gross domestic product (GDP) and electricity consumption can be used to effectively evaluate economic status and living standards of residents. Some scholars have estimated gridded GDP and electricity consumption. However, such gridded data have shortcomings, including overestimating real GDP growth, ignoring the heterogeneity of the spatiotemporal dynamics of the grid, and limited time-span. Simultaneously, the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS) and National Polar-orbiting Partnership's Visible Infrared Imaging Radiometer (NPP/VIIRS) nighttime light data, adopted in these studies as a proxy tool, still facing shortcomings, such as imperfect matching results, discontinuity in temporal and spatial changes. In this study, we employed a series of methods, such as a particle swarm optimization-back propagation (PSO-BP) algorithm, to unify the scales of DMSP/OLS and NPP/VIIRS images and obtain continuous 1 km × 1 km gridded nighttime light data during 1992-2019. Subsequently, from a revised real growth perspective, we employed a top-down method to calculate global 1 km × 1 km gridded revised real GDP and electricity consumption during 1992-2019 based on our calibrated nighttime light data.

Exocyst controls exosome biogenesis via Rab11a.

Tumor cells actively release large quantities of exosomes, which pivotally participate in the regulation of cancer biology, including head and neck cancer (HNC). Exosome biogenesis and release are complex and elaborate processes that are considered to be similar to the process of exocyst-mediated vesicle delivery. By analyzing the expression of exocyst subunits and their role in patients with HNC, we aimed to identify exocyst and its functions in exosome biogenesis and investigate the molecular mechanisms underlying the regulation of exosome transport in HNC cells. We observed that exocysts were highly expressed in HNC cells and could promote exosome secretion in these cells. In addition, downregulation of exocyst expression inhibited HN4 cell proliferation by reducing exosome secretion. Interestingly, immunofluorescence and electron microscopy revealed the accumulation of multivesicular bodies (MVBs) after the knockdown of exocyst. Autophagy, the major pathway of exosome degradation, is not activated by this intracellular accumulation of MVBs, but these MVBs are consumed when autophagy is activated under the condition of cell starvation. Rab11a, a small GTPase that is involved in MVB fusion, also interacted with the exocyst. These findings suggest that the exocyst can regulate exosome biogenesis and participate in the malignant behavior of tumor cells.

Structural Alternation in Heat Shock Proteins of Activated Macrophages.

The inflammatory response of macrophages is an orderly and complex process under strict regulation accompanied by drastic changes in morphology and functions. It is predicted that proteins will undergo structural changes during these finely regulated processes. However, changes in structural proteome in macrophages during the inflammatory response remain poorly characterized. In the present study, we applied limited proteolysis coupled mass spectrometry (LiP-MS) to identify proteome-wide structural changes in lipopolysaccharide (LPS)-activated macrophages. We identified 386 structure-specific proteolytic fingerprints from 230 proteins. Using the Gene Ontology (GO) biological process enrichment, we discovered that proteins with altered structures were enriched into protein folding-related terms, in which HSP60 was ranked as the most changed protein. We verified the structural changes in HSP60 by using cellular thermal shift assay (CETSA) and native CETSA. Our results showed that the thermal stability of HSP60 was enhanced in activated macrophages and formed an HSP10-less complex. In conclusion, we demonstrate that in situ structural systems biology is an effective method to characterize proteomic structural changes and reveal that the structures of chaperone proteins vary significantly during macrophage activation.

Orai-vascular endothelial-cadherin signaling complex regulates high-glucose exposure-induced increased permeability of mouse aortic endothelial cells.

INTRODUCTION: Diabetes-associated endothelial barrier function impairment might be linked to disturbances in Ca2+ homeostasis. To study the role and molecular mechanism of Orais-vascular endothelial (VE)-cadherin signaling complex and its downstream signaling pathway in diabetic endothelial injury using mouse aortic endothelial cells (MAECs). RESEARCH DESIGN AND METHODS: The activity of store-operated Ca2+ entry (SOCE) was detected by calcium imaging after 7 days of high-glucose (HG) or normal-glucose (NG) exposure, the expression levels of Orais after HG treatment was detected by western blot analysis. The effect of HG exposure on the expression of phosphorylated (p)-VE-cadherin and VE-cadherin on cell membrane was observed by immunofluorescence assay. HG-induced transendothelial electrical resistance was examined in vitro after MAECs were cultured in HG medium. FD-20 permeability was tested in monolayer aortic endothelial cells through transwell permeability assay. The interactions between Orais and VE-cadherin were detected by co-immunoprecipitation and immunofluorescence technologies. Immunohistochemical experiment was used to detect the expression changes of Orais, VE-cadherin and p-VE-cadherin in aortic endothelium of mice with diabetes. RESULTS: (1) The expression levels of Orais and activity of SOCE were significantly increased in MAECs cultured in HG for 7 days. (2) In MAECs cultured in HG for 7 days, the ratio of p-VE-cadherin to VE-cadherin expressed on the cell membrane and the FD-20 permeability in monolayer endothelial cells increased, indicating that intercellular permeability increased. (3) Orais and VE-cadherin can interact and enhance the interaction ratio through HG stimulation. (4) In MAECs cultured with HG, the SOCE activator ATP enhanced the expression level of p-VE-cadherin, and the SOCE inhibitor BTP2 decreased the expression level of p-VE-cadherin. (5) Significantly increased expression of p-VE-cadherin and Orais in the aortic endothelium of mice with diabetes. CONCLUSION: HG exposure stimulated increased expression of Orais in endothelial cells, and increased VE-cadherin phosphorylation through Orais-VE-cadherin complex and a series of downstream signaling pathways, resulting in disruption of endothelial cell junctions and initiation of atherosclerosis.

China's city-level carbon emissions during 1992-2017 based on the inter-calibration of nighttime light data.

Accurate, long-term, full-coverage carbon dioxide (CO2) data in units of prefecture-level cities are necessary for evaluations of CO2 emission reductions in China, which has become one of the world's largest carbon-emitting countries. This study develops a novel method to match satellite-based Defense Meteorological Satellite Program's Operational Landscan System (DMSP/OLS) and Suomi National Polar-orbiting Partnership's Visible Infrared Imaging Radiometer Suite (NPP/VIIRS) nighttime light data, and estimates the CO2 emissions of 334 prefecture-level cities in China from 1992 to 2017. Results indicated that the eastern and coastal regions had higher carbon emissions, but their carbon intensity decreased more rapidly than other regions. Compared to previous studies, we provide the most extensive and long-term CO2 dataset to date, and these data will be of great value for further socioeconomic research. Specifically, this dataset provides a foundational data source for China's future CO2 research and emission reduction strategies. Additionally, the methodology can be applied to other regions around the world.

County-level CO2 emissions and sequestration in China during 1997-2017.

With the implementation of China's top-down CO2 emissions reduction strategy, the regional differences should be considered. As the most basic governmental unit in China, counties could better capture the regional heterogeneity than provinces and prefecture-level city, and county-level CO2 emissions could be used for the development of strategic policies tailored to local conditions. However, most of the previous accounts of CO2 emissions in China have only focused on the national, provincial, or city levels, owing to limited methods and smaller-scale data. In this study, a particle swarm optimization-back propagation (PSO-BP) algorithm was employed to unify the scale of DMSP/OLS and NPP/VIIRS satellite imagery and estimate the CO2 emissions in 2,735 Chinese counties during 1997-2017. Moreover, as vegetation has a significant ability to sequester and reduce CO2 emissions, we calculated the county-level carbon sequestration value of terrestrial vegetation. The results presented here can contribute to existing data gaps and enable the development of strategies to reduce CO2 emissions in China.

Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells.

INTRODUCTION: Diabetes-associated endothelium dysfunction might be linked to disturbances in Ca2+ homeostasis. Our main objective is to reveal the potential mechanisms by which high-glucose (HG) exposure promotes increased proliferation of human coronary artery endothelial cells (HCAECs) in culture, and that store-operated Ca2+ entry (SOCE) and insulin-like growth factor binding protein 3 (IGFBP3) contribute to this proliferation. RESEARCH DESIGN AND METHODS: We detected the expression levels of Ca2+ release-activated calcium channel proteins (Orais), IGFBP3 and proliferating cell nuclear antigen of HCAECs cultured in HG medium for 1, 3, 7, and 14 days and in streptozotocin-induced diabetic mouse coronary endothelial cells. Coimmunoprecipitation and immunofluorescence technologies were used to detect the interactions between Orais and IGFBP3 of HCAECs exposed to HG environment, and to detect IGFBP3 expression and proliferation after treatment of HCAECs cultured in HG medium with an agonist or inhibitor of SOCE. Similarly, after transfection of specific small interfering RNA to knock down IGFBP3 protein expression, SOCE activity and Orais expression were tested. Some processes related to endothelial dysfunction, such as migration, barrier function and adhesion marker expression, are also measured. RESULTS: HG exposure promoted increased proliferation of HCAECs in culture and that SOCE and IGFBP3 contributed to this proliferation. In addition, we also found that Orais and IGFBP3 were physically associated and regulated each other's expression levels. Besides, their expression levels and interactions were enhanced in HCAECs after exposure to HG. HG exposure promotes cell migration, but reduces barrier function and adherens junction protein expression levels in HCAECs. CONCLUSION: Orais and IGFBP3 formed a signaling complex that mediated HCAEC proliferation during HG exposure in culture. Meanwhile, we also found that SOCE stimulates proliferation of HCAECs by regulating IGFBP3, thereby promoting the occurrence and progression of coronary atherosclerosis in diabetes. It is worth noting that our findings may shed new light on the mechanisms of increased proliferation in HCAECs in diabetes and suggest the potential value of SOCE and IGFBP3 as therapeutic targets for coronary atherosclerosis in individuals with diabetes.

Intelligent Occlusion Stabilization Splint with Stress-Sensor System for Bruxism Diagnosis and Treatment.

Bruxism is a masticatory muscle activity characterized by high prevalence, widespread complications, and serious consequences but without specific guidelines for its diagnosis and treatment. Although occlusal force-based biofeedback therapy is proven to be safe, effective, and with few side effects in improving bruxism, its mechanism and key technologies remain unclear. The purpose of this study was to research a real-time, quantitative, intelligent, and precise force-based biofeedback detection device based on artificial intelligence (AI) algorithms for the diagnosis and treatment of bruxism. Stress sensors were integrated and embedded into a resin-based occlusion stabilization splint by using a layering technique (sandwich method). The sensor system mainly consisted of a pressure signal acquisition module, a main control module, and a server terminal. A machine learning algorithm was leveraged for occlusal force data processing and parameter configuration. This study implemented a sensor prototype system from scratch to fully evaluate each component of the intelligent splint. Experiment results showed reasonable parameter metrics for the sensors system and demonstrated the feasibility of the proposed scheme for bruxism treatment. The intelligent occlusion stabilization splint with a stress sensor system is a promising approach to bruxism diagnosis and treatment.

Role of TRPP2 in mouse airway smooth muscle tension and respiration.

The transient receptor potential polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle-Pkd2 conditional knockout (Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed more shallowly and faster, and their cross-sectional area ratio of bronchi to accompanying pulmonary arteries was higher, suggesting that TRPP2 may regulate ASM tension and contribute to the occurrence of bronchiectasis in ADPKD. In a bioassay examining isolated tracheal ring tension, no significant difference was found for high-potassium-induced depolarization of the ASM between the two groups, indicating that TRPP2 does not regulate depolarization-induced ASM contraction. By contrast, carbachol-induced contraction of the ASM derived from Pkd2SM-CKO mice was significantly reduced compared with that in wild-type mice. In addition, relaxation of the carbachol-precontracted ASM by isoprenaline, a ß-adrenergic receptor agonist that acts through the cAMP/adenylyl cyclase pathway, was also significantly attenuated in Pkd2SM-CKO mice compared with that in wild-type mice. Thus, TRPP2 deficiency suppressed both contraction and relaxation of the ASM. These results provide a potential target for regulating ASM tension and for developing therapeutic alternatives for some ADPKD complications of the respiratory system or for independent respiratory disease, especially bronchiectasis.