Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update

Breast cancer is one of the leading causes of cancer-related death in women. Currently, the treatment of breast cancer is limited by the lack of effectively targeted therapy and patients often suffer from higher severity, metastasis, and resistance. Extracellular vesicles (EVs) consist of lipid bilayers that encapsulate a complex cargo, including proteins, nucleic acids, and metabolites. These bioactive cargoes have been found to play crucial roles in breast cancer initiation and progression. Moreover, EV cargoes play pivotal roles in converting mammary cells to carcinogenic cells and metastatic foci by extensively inducing proliferation, angiogenesis, pre-metastatic niche formation, migration, and chemoresistance. The present update review mainly discusses EVs cargoes released from breast cancer cells and tumor-derived EVs in the breast cancer microenvironment, focusing on proliferation, metastasis, chemoresistance, and their clinical potential as effective biomarkers

Causal associations of sleep traits with cancer incidence and mortality

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00–1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06–1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11–1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08–1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15–9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27–1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis

Targeting of the Human Coagulation Factor IX Gene at rDNA Locus of Human Embryonic Stem Cells

BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs) in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs) but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA) gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50%) and homologous recombination frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs

Organophosphate Pesticides and Pyrethroids in Farmland of the Pearl River Delta, China: Regional Residue, Distributions and Risks

A regional-scale survey was conducted to assess the occurrence, distribution, and risk of two extensively used pesticides (organophosphate pesticides and pyrethroids) in agricultural soils from the Pearl River Delta (PRD), South China. All target organophosphate pesticides (OPPs) and pyrethroids (PYs) were detected in the soil samples and both with a detection rate of 100%. The residues of the sum of six OPPs and the sum of four PYs were in the range of LOD–991 ng/g and 8.76–2810 ng/g, respectively. Dimethoate was the dominant OPPs, and fenpropathrin was the predominant PYs in the soils of the PRD region. With intensive agricultural activities, higher residues of OPPs and PYs in soils were detected closer to the seaside, among which Zhuhai city and Huizhou city suffered more serious combined pesticide pollution. The vertical compositional profiles showed that dimethoate could be detected through each soil layer in the PRD region’s nine cities. The human exposure estimation of OPPs showed insignificant risks to the local population. In contrast, cypermethrin and fenpropathrin showed a potential ecological risk of 2.5% and 3.75% of the sampling sites, respectively. These results can facilitate those commonly used pesticide controls and promote sustainable soil management

Encapsulation of Fe3O4 nanoparticles into N, S co-doped graphene sheets with greatly enhanced electrochemical performance

Particular N, S co-doped graphene/Fe3O4 hybrids have been successfully synthesized by the combination of a simple hydrothermal process and a subsequent carbonization heat treatment. The nanostructures exhibit a unique composite architecture, with uniformly dispersed Fe3O4 nanoparticles and N, S co-doped graphene encapsulant. The particular porous characteristics with many meso/micro holes/pores, the highly conductive N, S co-doped graphene, as well as the encapsulating N, S co-doped graphene with the high-level nitrogen and sulfur doping, lead to excellent electrochemical performance of the electrode. The N-S-G/Fe3O4 composite electrode exhibits a high initial reversible capacity of 1362.2 mAhg−1, a high reversible specific capacity of 1055.20 mAhg−1 after 100 cycles, and excellent cycling stability and rate capability, with specific capacity of 556.69 mAhg−1 when cycled at the current density of 1000 mAg−1, indicating that the N-S-G/Fe3O4 composite is a promising anode candidate for Li-ion batteries

Levels, Distribution and Health Risk Assessment of Organochlorine Pesticides in Agricultural Soils from the Pearl River Delta of China

To reveal the pollution status of agricultural soils along with rapid urbanization and economic growth, a large regional survey of organochlorine pesticides (OCPs) in agricultural soils was conducted in the Pearl River Delta (PRD) of China. The results showed that the total residues of 23 OCPs were in the range of ND-946 ng/g dry weight. OCP residues showed distinct spatial distribution characteristics within the PRD. OCPs were mainly found in areas with high agricultural production and industrial activities. Higher OCP concentrations were observed in the top layer of soil, while the concentration decreases to marginal levels when the soil depth is greater than 50 cm. OCPs are mainly derived from historical use. Hexachlorocyclohexanes (HCHs) in the top soil of the study area are mainly from the use of lindane. Soil pH was negatively and significantly correlated with total OCP concentration. The human health risk assessment showed no health risk for children, while for adults, there is a non-carcinogenic risk, which needs to be noticed. Agricultural activities and industrial production have made the region a pollution hotspot and should arouse more stringent regulation to protect the environment and food safety

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14(+)CD206(+)CD86(-) and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-beta expression. IFN-beta further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-beta promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-beta production induced through TLR4 ligation.Peer reviewe

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb. Keywords: Esophageal cancer, Germline variants, Somatic mutations, Association database, Chinese populatio

Remarkable active-site dependent H2O promoting effect in CO oxidation

International audienc