Top Ten Breakthroughs in Clinical Hypertension Research in 2022

Hypertension is a major global public health concern whose disease burden affects an estimated 1.4 billion people worldwide and is associated with 10.8 million deaths annually. Despite substantial advances in medical care, the prevalence of hypertension has markedly increased, owing to population aging; poor treatment adherence; and increases in risk factors, such as excessive salt intake, and overweight and obesity. Consequently, the disability-adjusted life years have increased by 40%, primarily because of elevated risk of stroke, coronary atherosclerosis, heart failure, and kidney failure. Major outstanding problems associated with the treatment and management of hypertension include determining optimal blood pressure targets, developing innovative antihypertensive medications and devices, and implementing effective and feasible hypertension management strategies. To address these challenges, numerous clinical trials are currently underway. This article highlights the most influential ten clinical studies on hypertension in 2022. The rational use of antihypertensive medications is concluded to be important for effective hypertension management. Important considerations include medication types and dosing times; optimal blood pressure targets; the development of new drugs and therapeutic devices; specific community characteristics, such as village doctor-led care; and healthful diets

Innate immunity of vascular smooth muscle cells contributes to two-wave inflammation in atherosclerosis, twin-peak inflammation in aortic aneurysms and trans-differentiation potential into 25 cell types

IntroductionVascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in aortic diseases. Innate immunity is the main driving force for cardiovascular diseases. MethodsTo determine the roles of innate immunity in VSMC and aortic pathologies, we performed transcriptome analyses on aortas from ApoE–/– angiotensin II (Ang II)-induced aortic aneurysm (AAA) time course, and ApoE–/– atherosclerosis time course, as well as VSMCs stimulated with danger-associated molecular patterns (DAMPs).ResultsWe made significant findings: 1) 95% and 45% of the upregulated innate immune pathways (UIIPs, based on data of 1226 innate immune genes) in ApoE–/– Ang II-induced AAA at 7 days were different from that of 14 and 28 days, respectively; and AAA showed twin peaks of UIIPs with a major peak at 7 days and a minor peak at 28 days; 2) all the UIIPs in ApoE–/– atherosclerosis at 6 weeks were different from that of 32 and 78 weeks (two waves); 3) analyses of additional 12 lists of innate immune-related genes with 1325 cytokine and chemokine genes, 2022 plasma membrane protein genes, 373 clusters of differentiation (CD) marker genes, 280 nuclear membrane protein genes, 1425 nucleoli protein genes, 6750 nucleoplasm protein genes, 1496 transcription factors (TFs) including 15 pioneer TFs, 164 histone modification enzymes, 102 oxidative cell death genes, 68 necrotic cell death genes, and 47 efferocytosis genes confirmed two-wave inflammation in atherosclerosis and twin-peak inflammation in AAA; 4) DAMPs-stimulated VSMCs were innate immune cells as judged by the upregulation of innate immune genes and genes from 12 additional lists; 5) DAMPs-stimulated VSMCs increased trans-differentiation potential by upregulating not only some of 82 markers of 7 VSMC-plastic cell types, including fibroblast, osteogenic, myofibroblast, macrophage, adipocyte, foam cell, and mesenchymal cell, but also 18 new cell types (out of 79 human cell types with 8065 cell markers); 6) analysis of gene deficient transcriptomes indicated that the antioxidant transcription factor NRF2 suppresses, however, the other five inflammatory transcription factors and master regulators, including AHR, NF-KB, NOX (ROS enzyme), PERK, and SET7 promote the upregulation of twelve lists of innate immune genes in atherosclerosis, AAA, and DAMP-stimulated VSMCs; and 7) both SET7 and trained tolerance-promoting metabolite itaconate contributed to twin-peak upregulation of cytokines in AAA. DiscussionOur findings have provided novel insights on the roles of innate immune responses and nuclear stresses in the development of AAA, atherosclerosis, and VSMC immunology and provided novel therapeutic targets for treating those significant cardiovascular and cerebrovascular diseases

Robust reproduction of sound zones with local sound orientation

Pressure matching (PM) and planarity control (PC) methods can be used to re- produce local sound with a certain orientation at the listening zone, while suppressing the sound energy at the quiet zone. In this letter, regularized PM and PC, incorporating coarse error estimation, are introduced to increase the robustness in non-ideal reproduction scenarios. Facilitated by this, the interaction between regularization, robustness, (tuned) personal audio optimization and local directional performance is explored. Simulations show that under certain conditions, PC and weighted PM achieve comparable performance, while PC is more robust to a poorly selected regularization parameter

GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma

Abstract Background Lung adenocarcinoma is the most common type of lung cancer and one of the most lethal and prevalent cancers. Aberrant glycosylation was common and essential in tumorigenesis, with fucosylation as one of the most common types disrupted in cancers. However, it is still unknown whether genes involved in fucosylation are important for lung adenocarcinoma development and process. Methods GMDS is involved in cellular fucosylation. Here we examined GMDS expression level at both mRNA and protein level in lung adenocarcinoma. The impact of GMDS knockdown on lung adenocarcinoma in vitro and in vivo was investigated. Transcriptome changes with GMDS knockdown in lung adenocarcinoma cells were also examined to provide insights into related molecular mechanisms. Results GMDS expression is significantly upregulated in lung adenocarcinoma at both mRNA and protein levels. Lentivirus-mediated shRNA strategy inhibited GMDS expression efficiently in human lung adenocarcinoma cells A549 and H1299, and GMDS knockdown impaired cell proliferation, colony formation ability, induced cell cycle arrest, and apoptosis in both cell lines. Furthermore, GMDS knockdown inhibited tumorigenesis in a xenograft mice model of lung adenocarcinoma. Microarray analysis explored the GMDS-mediated molecular network and revealed that the CASP8-CDKN1A axis might be critical for lung adenocarcinoma development. Conclusions These findings suggest that GMDS upregulation is critical for cell proliferation and survival in human lung adenocarcinoma and might serve as a potential biomarker for lung adenocarcinoma diagnosis and treatment

Additional file 1: of GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma

Figure S1. Cell cycle arrest in human lung adenocarcinoma cell lines with GMDS knockdown 48 h after lentiviral infection. a-b. Cell cycle distribution in A549 cells (a) and H1299 cells (b) infected with lentivirus expressing either Scr-shRNA or GMDS-shRNA. Both cells infected with lentivirus expressing either Scr-shRNA or GMDS-shRNA were cultured for 48 h. After propidium iodide (PI) staining, cell cycle distribution was analyzed with flow cytometry. The graph represents the mean ± SEM of cell proportion in the G1 phase, S phase and G2/M phase from three independent experiments (*, p < 0.05; **, p < 0.01). (DOCX 151 kb

Additional file 1 of Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis

Supplementary Material 1: Hydrodynamic size distribution of RPPs by DLS (Figure S1); The magnetothermal effect of the nanosystem (Figure S2);UV − vis absorption spectra of RPPs and the encapsulation efficiency and loading efficiency of RPPs (Figure S3); Cell viabilities after incubation with SPIOs, RPPs and SPIOs + RPPs (Figure S4);CCK-8 assay of the cellular inhibition rate after different treatments (Figure S5); Morphology of BMDCs under optical microscope (Figure S6); Representative images of H&E staining, TUNEL, and Ki67 immunostaining of tumour slices after different treatments (Figure S7); The analysis of tumour growth after different treatments (Figure S8); Biosafety analysis of SPIOs + RPPs in vivo (Figure S9); CD8 + immunostaining of distant metastatic tumour slices after different treatments (Figure S10). (PDF