Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment (TME) which are closely associated with the tumor malignant progression. However, the regulatory mechanisms by which TAMs influence the progression of triple-negative breast cancer (TNBC) remain unclear. Here, we report that hepatic leukemia factor (HLF) acts as a novel oncoprotein in TNBC. We found that HLF was regulated by transforming growth factor-beta1 (TGF-β1) that is secreted by TAMs. Then, HLF transactivated gamma-glutamyltransferase 1 (GGT1) to promote the ferroptosis resistance, thus driving TNBC cell proliferation, metastasis and cisplatin resistance. Reciprocally, IL-6 produced by TNBC cells activated the JAK2/STAT3 axis to induce TGF-β1 secretion by TAMs, thus constituted a feed-forward circuit. The accuracy of TNBC patient prognosis could be improved by employing a combination of HLF and GGT1 values. Thus, our findings document that the interactive dialogue between TNBC cells and TAMs promotes sustained activation of HLF in tumor cells through the IL-6-TGF-β1 axis. Subsequently, HLF promotes the ferroptosis resistance in TNBC cells via GGT1 and ultimately facilitates the malignant tumor progression. Our study provides a potential target for the treatment of TNBC.

No abstract

Graphene family nanomaterials, with superior mechanical, chemical, and biological properties, have grabbed appreciable attention on the path of researches seeking new materials for future biomedical applications. Although potential applications of graphene had been highly reviewed in other fields of medicine, especially for their antibacterial properties and tissue regenerative capacities, in vivo and in vitro studies related to dentistry are very limited. Therefore, based on current knowledge and latest progress, this article aimed to present the recent achievements and provide a comprehensive literature review on potential applications of graphene that could be translated into clinical reality in dentistry.

In this study, we describe a new strategy for producing narrowly dispersed functional colloidal particles stabilized by a nanocomposite with hydrophilic clay faces and hydrophobic polystyrene (PS) brushes on the edges. This method involves preparation of polymer brushes on the edges of clay layers and Pickering suspension polymerization of styrene in the presence of the nanocomposites. PS brushes on the edges of clay layers were prepared by atom transfer radical polymerization. X-ray diffraction and thermogravimetric analysis results indicated that PS chains were grafted to the edges of clay platelets. Transmission electron microscope results showed that different morphologies of clay-PS particles could be obtained in different solvents. In water, clay-PS particles aggregated together, in which PS chains collapsed forming nanosized hydrophobic domains and hydrophilic clay faces stayed in aqueous phase. In toluene, clay-PS particles formed face-to-face structure. Narrowly dispersed PS colloidal particles stabilized by clay-PS were prepared by suspension polymerization. Because of the negatively charged clay particles on the surface, the zeta potential of the PS colloidal particles was negative. Positively charged poly(2-vinyl pyridine) (P2VP) chains were adsorbed to the surface of PS colloidal particles in aqueous solution at a low pH value, and gold nanoparticles were prepared in P2VP brushes. Such colloidal particles may find important applications in a variety of fields including waterborne adhesives, paints, catalysis of chemical reactions, and protein separation. V

Background The aim of this study was to investigate the relationship between Talin-1 and stability of carotid atherosclerosis plaque and also find out the role of miRNA, as an upstream regulator, in regulating the expression level of Talin-1. Methods Human carotid plaques were obtained from 20 symptomatic carotid stenosis patients who underwent carotid endarterectomy (CEA) in our hospital between October 2014 and August 2017. Western blot analysis and immunohistochemistry was carried out to detect the distribution and expression level of Talin-1 in each plaque sample. The content of miRNAs in carotid plaque was decected by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the relative expression levels were calculated by 2 -△△Ct method after the (cycle threshold) Ct value (power amplification knee point) was obtained. Dual-luciferase reporter assays were applied to verify the successful transfections. Finally, we compared all the groups with independent-samples t-test and one-way analysis of variance (ANOVA). Results Talin-1 was significantly downregulated in human unstable carotid plaque samples compared with stable carotid plaques ( P < 0.05), and the distribution of Talin-1 was mainly found in the fibrous cap of carotid plaque. The overexpression of miRNA-330-5p was found in unstable carotid plaque, which significantly induced the inhibition of expression level of Talin-1. Conclusion Upregulated miR-330-5p may lead to unstable carotid plaques by targeting Talin-1 in symptomatic carotid stenosis patients. This might be a new target for the treatment of atherosclerotic diseases through future studies.

BackgroundThis study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function.MethodsHuman aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample. We inhibited the expression of Talin-1 via RNA interference in VSMCs. VSMC proliferation was detected by Cell-counting Kit-8 analyses. Scratch test and flow cytometry were used to identify the migration and apoptosis ability. Antibody microarray analysis and qRT-PCR were used to detect some protein and mRNA changes which were induced by Talin-1 downregulation.ResultsTalin-1 was significantly downregulated in the media of aortic dissection samples compared with controls (P < 0.05). Talin-1 knockdown significantly induced VSMC proliferation and migration in vitro. Proteins which involved in cell cycle can be regulated by downregulating Talin-1. Down regulation of Talin-1 can significanly increased the expression of anaphase-promoting complex subunit 2 (APC2) and decreased p19 alternative reading frame (p19ARF), Cullin-3, and beta actin’s expression.ConclusionsTalin-1 induces VSMCs proliferation and migration. It downregulated in aortic dissection, which might play a potential role in the development of aortic dissection.

Increasing researches suggest that inflammatory response is involved in vascular remodeling, which plays an important role in the development of aortic dissection. Glucocorticoids have been widely used in the clinical practice due to its powerful and effective anti-inflammatory property. However, the potential relationship between glucocorticoids and aortic dissection was still obscure. This study sought to elucidate the effect of glucocorticoids on the development and progression of aortic dissection, and the potential mechanism involved. Serum cortisol in aortic dissection patients was significantly higher than that in non-ruptured aortic aneurysm patients and healthy volunteers by radioimmunoassay. In modified C57BL/6 mouse model of aortic dissection, glucocorticoids reduced the incidence of aortic dissection and protected the collagen from degradation. Furthermore, glucocorticoids inhibited the TNF-α secretion of THP-1 monocytes, decreased the migration, phenotype switch from contractile type to synthetic type, and the apoptosis of human aortic smooth muscle cells induced by TNF-α. Finally, TNF-sRII was identified as an important cytokine in cellular interaction that participated in vascular remodeling by targeting the p38 MAPK-HSP27 pathway. These results indicate that glucocorticoids inhibit the incidence of aortic dissection by decreasing the TNF-α secretion and increasing the uncombined TNF-sRII, positively participating in vascular remodeling.