Many aspects of human health and disease are influenced by sex as a biological variable and gender as a social construct. A recent study from Nature Communications reported the landscape of outcome ...comparisions by sex in oncology clinical trials, highlighting the need for a more thorough reporting of sex differences.
Exosomes are considered promising indicators for early cancer diagnosis. The multiple protein biomarkers carried by exosomes are associated with diverse significant biological processes and are ...important biomarkers of cancer subtypes. However, it is challenging to sensitively and accurately quantify protein biomarkers from a few exosomes. Herein, we propose an ultrasensitive method for quantitatively profiling protein biomarkers on the surface of exosomes by integrating mass spectrometry imaging and gold nanoparticle (AuNP)-based signal amplification. Organic oligomers as mass tags and specific antibodies are modified on AuNPs to form biomarker probes. Exosomes captured by the antibody-coated gold chip are recognized by the AuNPs probes, forming a sandwich immunoassay. By mass spectrometry imaging the mass tags, multiple protein biomarkers can be quantitatively detected from the exosomes, with a limit-of-detection (LOD) down to 50 exosome particles. As a proof of concept, exosomes secreted by different breast-cancer cell subtypes, i.e. MCF-7 and MDA-MB231, were distinguished by the level of surface protein biomarkers of CD9, CD44, and epithelial cell adhesion molecule (EpCAM) acquired by the method, demonstrating that exosomes could be used for the diagnosis of cancer at subtype level. In consideration of the advantages of the ultrasensitivity, accuracy, and simplicity, the strategy has potential prospects in biomarker discovery, cellular phenotype characterization, and cancer diagnosis.
Precise and rapid monitoring of metabolites in biofluids is a desirable but unmet goal for disease diagnosis and management. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) ...exhibits advantages in metabolite analysis. However, the low accuracy in quantification of the technique limits its transformation to clinical usage. We report herein the use of Au nanoparticle arrays self-assembled at liquid–liquid interfaces for mass spectrometry (MS)-based quantitative biofluids metabolic profiling. The two-dimensional arrays feature uniformly and closely packed Au nanoparticles with 3 nm interparticle gaps. The experimental study and theoretical simulation show that the arrays exhibit high photothermal conversion and heat confinement effects, which enhance the laser desorption/ionization efficacy. With the nanoscale roughness, the AuNP arrays as laser desorption/ionization substrates can interrupt the coffee-ring effect during droplet evaporation. Therefore, high reproducibility (RSD <5%) is obtained, enabling accurate quantitative analysis of diverse metabolites from 1 μL of biofluids in seconds. By quantifying glucose in the cerebrospinal fluid (CSF), it allows us to identify patients with brain infection and rapidly evaluate the clinical therapy response. Consequently, the method shows potential in advanced metabolite analysis and biomedical diagnostics.
TGF-β, a negative cytokine, exerts critical roles in shaping immunosuppressive TME, thereby promoting tumor progression and resistance 1. ...evolving approaches to blocking TGF-β signaling in CAR-T ...cell therapy have been emerging, such as combining with TGF-β-targeted neutralizing antibodies or small molecule inhibitors, directly deleting TGF-βRII via CRISPR/Cas9 technology, or co-expressing a dominant-negative TGF-β receptor II (DNTGF-βRII). Table S2). ...solid tumors were ideal indications for DNTGF-βR armored CAR-T cell therapy due to the crucial negative role of TGF-β in TME (Fig. 1D). Additionally, a recent study reported that a CD200R-CD28 switch optimally outperformed in enhancing CAR-T function in CD200 + multiple myeloma (MM) models than the approach of CD200R-dominant negative 6.
Background:
Exercise is medicine. Multiple studies on the effects and mechanisms of exercise in treating depression among teenagers and adolescents have been widely reported. However, literature ...involving scientometric analysis of this topic is sparse. Here, we endeavored to conduct a bibliometric study and visualization analysis to give a bird's-eye view of publications between 2000 and 2020 on exercise therapy treating depression.
Methods:
Relevant original publications were obtained from the Science Citation Index Expanded in the Web of Science Core Collection (WoSCC) database between 2000 and 2020. CiteSpace (5.7.R 5) and VOSviewer (1.6.16) software were used to perform bibliometric analysis of countries, institutions, categories, journals, authors, references, and keywords involved in this topic.
Results:
A total number of 975 articles on this field were retrieved from the WoSCC database and we identified an overall increase in the amount of publications over the past two decades, with the United States and Harvard University leading the field. Most related publications were published in the journals with a focus on sport, medicine, rehabilitation, psychology, and health, as represented by the dual-map overlay. A series of authors and co-cited authors were identified as main contributors in the exercise-depression-teenager domain. Three major clusters were explored based on the reference co-citation analysis: “exercise,” “suicide,” and “concussion”.
Conclusions:
Current concerns and hotspots of exercise intervention in depression treatments were summarized by “individual level,” “social level,” “role of exercise,” and “research quality.” We considered that the following four directions were potential future perspectives: “research on the effect of specific exercise intervention,” “research on the essence of exercise and sports,” “research on the combination mode of ‘exercise + X',” and “research on the micro and molecular level,” which should receive more attention.
•HRW can reduce the rot incidence inhibited the respiration intensity of kiwifruit.•HRW delays the decrease of firmness by alleviating pectin solubilization in kiwifruit.•HRW reduces the lipid ...peroxidation level and activates superoxide dismutase in kiwifruit.•HRW excites the radical scavenging activities in kiwifruit.
The effect of hydrogen-rich water (HRW) on prolonging the shelf life of kiwifruit and possible underlying mechanisms were assessed. Our results revealed that HRW (30%, 80%, and 100%) displayed different effects in inhibiting the rot of kiwifruit. Among these treatments, 80% HRW had the most significant effect by decreasing the rot incidence and preserving the firmness of kiwifruit. This conclusion was supported by the fact that 80% HRW treatment could effectively alleviate pectin solubilization and reduce the activities of cell wall-degrading enzymes. On the other hand, HRW treatment was able to reduce the respiration intensity, increase the activity of superoxide dismutase, decrease lipid peroxidation level, and maintain the radical (DPPH,O2-,andOH)-scavenging activity of kiwifruit. Moreover, the inner membrane of mitochondria exhibited higher integrity. Thus, our results demonstrate that HRW treatment could delay fruit ripening and senescence during storage by regulating the antioxidant defence.
Abstract
Exposure to extreme temperatures or fine particles is associated with adverse health outcomes but their interactive effects remain unclear. We aimed to explore the interactions of extreme ...temperatures and PM
2.5
pollution on mortalities. Based on the daily mortality data collected during 2015–2019 in Jiangsu Province, China, we conducted generalized linear models with distributed lag non-linear model to estimate the regional-level effects of cold/hot extremes and PM
2.5
pollution. The relative excess risk due to interaction (RERI) was evaluated to represent the interaction. The relative risks (RRs) and cumulative relative risks (CRRs) of total and cause-specific mortalities associated with hot extremes were significantly stronger (
p
< 0.05) than those related to cold extremes across Jiangsu. We identified significantly higher interactions between hot extremes and PM
2.5
pollution, with the RERI range of 0.00–1.15. The interactions peaked on ischaemic heart disease (RERI = 1.13 95%CI: 0.85, 1.41) in middle Jiangsu. For respiratory mortality, RERIs were higher in females and the less educated. The interaction pattern remained consistent when defining the extremes/pollution with different thresholds. This study provides a comprehensive picture of the interactions between extreme temperatures and PM
2.5
pollution on total and cause-specific mortalities. The projected interactions call for public health actions to face the twin challenges, especially the co-appearance of hot extremes and PM pollution.
The prognostic value of copper homeostasis-related genes in breast cancer (BC) remains largely unexplored. We analyzed copper homeostasis-related gene profiles within The Cancer Genome Atlas Program ...breast cancer cohorts and performed correlation analysis to explore the relationship between copper homeostasis-related mRNAs (chrmRNA) and lncRNAs. Based on these results, we developed a gene signature-based risk assessment model to predict BC patient outcomes using Cox regression analysis and a nomogram, which was further validated in a cohort of 72 BC patients. Using the gene set enrichment analysis, we identified 139 chrmRNAs and 16 core mRNAs via the Protein-Protein Interaction network. Additionally, our copper homeostasis-related lncRNAs (chrlncRNAs) (PINK1.AS, OIP5.AS1, HID.AS1, and MAPT.AS1) were evaluated as gene signatures of the predictive model. Kaplan-Meier survival analysis revealed that patients with a high-risk gene signature had significantly poorer clinical outcomes. Receiver operating characteristic curves showed that the prognostic value of the chrlncRNAs model reached 0.795 after ten years. Principal component analysis demonstrated the capability of the model to distinguish between low- and high-risk BC patients based on the gene signature. Using the pRRophetic package, we screened out 24 anticancer drugs that exhibited a significant relationship with the predictive model. Notably, we observed higher expression levels of the four chrlncRNAs in tumor tissues than in the adjacent normal tissues. The correlation between our model and the clinical characteristics of patients with BC highlights the potential of chrlncRNAs for predicting tumor progression. This novel gene signature not only predicts the prognosis of patients with BC but also suggests that targeting copper homeostasis may be a viable treatment strategy.
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