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Abstract Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstrated prominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported. In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD (Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation. We revealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylated MNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, but no related pathological change was found. Both MNPs are not mutagenic, while recoverable mild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrated a research approach for the non-clinical safety evaluation of nanoparticles. It also provided comprehensive valuable safety data for PEGylated and p-PEGylated MNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications in the cancer diagnosis and therapy.

IntroductionAir pollution imposes a significant burden on public health. Compared with the popular air quality index (AQI), the air quality health index (AQHI) provides a more comprehensive approach to measuring mixtures of air pollutants and is suitable for overall assessments of the short-term health effects of such mixtures.MethodsWe established an AQHI and cumulative risk index (CRI)-AQHI for Tianjin using single–and multi-pollutant models, respectively, as well as environmental, meteorological, and daily mortality data of residents in Tianjin between 2018 and 2020.Results and discussionCompared with the AQI, the AQHI and CRI-AQHI established herein correlated more closely with the exposure-response relationships of the total mortality effects on residents. For each increase in the interquartile range of the AQHI, CRI-AQHI and AQI, the total daily mortality rates increased by 2.06, 1.69 and 0.62%, respectively. The AQHI and CRI-AQHI predicted daily mortality rate of residents more effectively than the AQI, and the correlations of AQHI and CRI-AQHI with health were similar. Our AQHI of Tianjin was used to establish specific (S)-AQHIs for different disease groups. The results showed that all measured air pollutants had the greatest impact on the health of persons with chronic respiratory diseases, followed by lung cancer, and cardiovascular and cerebrovascular diseases. The AQHI of Tianjin established in this study was accurate and dependable for assessing short-term health risks of air pollution in Tianjin, and the established S-AQHI can be used to separately assess health risks among different disease groups.

Breast cancer is currently the most frequent malignant tumor and the leading cause of cancer death among women globally. Although the five-year survival rate for early breast cancer has risen to more than 90%, medication resistance persists in advanced breast cancer and some intractable breast cancer, resulting in a poor prognosis, a high recurrence rate, and a low survival rate. Single-cell sequencing (SCS) is the study of a single cell's gene structure and expression level differences in order to discover unusual molecular subgroups, disease development, and a variety of mechanisms. This review briefly discusses single-cell sequencing and its application, and lists the research on single-cell sequencing in the development and metastasis of breast cancer, in order to bring fresh ideas for the comprehensive treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Lithium (Li) metal anodes have received sustained attention due to their remarkable theoretical specific capacities and low electrochemical potentials. However, the nucleation and growth of Li dendrites during cycling have hindered their application in Li metal batteries (LMBs). As an indispensable battery component, separators offer an ideal platform for mitigating Li dendrites. Herein, an ion‐management membrane (IMM) concept utilizing polydopamine (PDA)‐modified polyetherimide track‐etched membranes (PEITEMs) is proposed. The PDA@PEITEM‐based IMM features vertically aligned uniform electronegative nanochannels, serving as ion distributors and "Li‐ion guides" to simultaneously smooth ion concentration fluctuations and accelerate Li+ selective conduction. The IMM's unique structural and chemical properties yield exceptional ionic conductivity (0.73 mS cm−1) and high Li+ transfer number (0.80) while minimizing Li+ concentration fluctuations. When employed in Li/Cu cells, the IMM facilitates a Coulombic efficiency exceeding 96% over 100 cycles at 0.5 mA cm−2. Moreover, it extends the cycle lifespan of Li/Li cells to 1 200 h at 1.0 mA cm−2. For Li/LiFePO4 cells, this approach enables a specific capacity of 146 mAh g−1, maintaining capacity retention of 79.84% after 1 000 cycles. This novel strategy for constructing free‐standing functional separators is convenient, efficient, and scalable, providing valuable insights into multifunctional separators for dendrite‐free LMBs. [ABSTRACT FROM AUTHOR]

The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118–2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145–0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019–0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042–2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration. [ABSTRACT FROM AUTHOR]

Background: There are currently no uniform treatments for post-stroke comorbid cognitive impairment and depression (PSCCID). Objective: To verify whether repetitive transcranial magnetic stimulation (rTMS) can improve PSCCID symptoms and explore the underlying roles of resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Thirty PSCCID patients were randomized in a 1 : 1 ratio to receive 4 weeks of rTMS (intervention group) or sham rTMS (control group) over the left dorsolateral prefrontal cortex (DLPFC). rs-fMRI was acquired to analyze the functional plasticity of brain regions at baseline and immediately after the last intervention. Results: Cognition, depression status, and neural electrophysiology were improved in both intervention and control groups after treatment (p = 0.015–0.042), and the intervention group had more significant improvement than the control group. Analysis of functional connectivities (FCs) within the default mood network (DMN) showed that the connection strength of the left temporal pole/left parahippocampal cortex and right lateral temporal cortex/right retrosplenial cortex in the intervention group were enhanced compared with its pre-intervention and that in the control group after treatment (p < 0.05), and the both FC values were positively correlated with MMSE scores (p < 0.001). The intervention group had stronger FCs within the DMN compared with the control group after treatment, and some of the enhanced FCs were correlated with the P300 latency and amplitude. Conclusions: rTMS over the left DLPFC is an effective treatment for improving both cognitive impairment and depression among patients with PSCCID. The enhanced FCs within the DMN may serve as a compensatory functional recombination to promote clinical recovery. [ABSTRACT FROM AUTHOR]

The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.

Handan is a typical city affected by regional particulate pollution. In order to investigate particulate matter (PM) characterization, source contributions and health risks for the general populations, we collected PM samples at two sites affected by a pollution event (12–18 May 2020) during the COVID-19 pandemic and analyzed the major components (SNA, OCEC, WSIIs, and metal elements). A PCA-MLR model was used for source apportionment. The carcinogenic and non-carcinogenic risks caused by metal elements in the PM were assessed. The results show that the renewal of old neighborhoods significantly influences local PM, and primarily the PM10; the average contribution to PM10 was 27 μg/m3. The source apportionment has indicated that all other elements came from dust, except Cd, Pb and Zn, and the contribution of the dust source to PM was 60.4%. As PM2.5 grew to PM10, the PM changed from basic to acidic, resulting in a lower NH4+ concentration in PM10 than PM2.5. The carcinogenic risk of PM10 was more than 1 × 10−6 for both children and adults, and the excess mortality caused by the renewal of the community increased by 23%. Authorities should pay more attention to the impact of renewal on air quality. The backward trajectory and PSCF calculations show that both local sources and short-distance transport contribute to PM—local sources for PM10, and short-distance transport in southern Hebei, northern Henan and northern Anhui for PM2.5, SO2 and NO2.

Abstract To understand the genotoxicity induced in the liver by silver nanoparticles (AgNPs) and silver ions, an engineered gold nanorod core/silver shell nanostructure (Au@Ag NR) and humanized hepatocyte HepaRG cells were used in this study. The involvement of oxidative stress and cell cycle arrest in the DNA and chromosome damage induced by 0.4–20 µg mL−1 Au@Ag NR were investigated by comet assay, γ-H2AX assay and micronucleus test. Further, the distribution of Au@Ag NR was analyzed. Our results demonstrated that both Ag+ and Au@Ag NR led to DNA cleavage and chromosome damage (clastogenicity) in HepaRG cells and that the Au@Ag NR retained in the nucleus may further release Ag+, aggravating the damages, which are mainly caused by cell cycle arrest and ROS formation. The results reveal the correlation between the intracellular accumulation, Ag+ ion release and the potential genotoxicity of AgNPs.

Air pollution places a considerable disease burden on the public. Compared with the widely applied air quality index (AQI), the air quality health index (AQHI) provides a more comprehensive measure of multiple pollutants. In this study, AQHI was constructed using environmental data, meteorological data, and the daily mortality data of Beijing residents from 2018 to 2020. Factors increasing the susceptibility of the population to the health effects of air pollution were identified to aid the construction of a specific AQHI (S-AQHI) for susceptible populations. The findings indicated that older adults, women, and people with respiratory disease are more susceptible to the short-term health effects of air pollution. The relative deviation in the AQHI and S-AQHI for changes in daily mortality percentage of various specific populations ranged from only 1.4% to 10.3%, indicating the universality of the AQHI in its capacity to predict health risks. The Spearman coefficient of correlation between the AQHI and AQI was 0.78 (p < 0.01). Each increase in the interquartile range of the AQHI and AQI results in an increase of 1.894% and 1.029% in the total daily mortality, respectively, demonstrating the stronger capacity of the AQHI to predict daily mortality compared to the AQI.

As a widely applied nanomaterial, silver nanomaterials (AgNMs) have increased public concern about their potential adverse biological effects. However, there are few related researches on the long-term toxicity, especially on the reversibility of AgNMs in vivo. In the current study, this issue was tackled by exploring liver damage after an intravenous injection of silver nanorods with golden cores (Au@AgNRs) and its potential recovery in a relatively long term (8 w). After the administration of Au@AgNRs into rats, Ag was found to be rapidly cleared from blood within 10 min and mainly accumulated in liver as well as spleen until 8 w. All detected parameters almost displayed a two-stage response to Au@AgNRs administration, including biological markers, histological changes and metabolic variations. For the short-term (2 w) responses, some toxicological parameters (hematological changes, cytokines, liver damages etc.) significantly changed compared to control and AuNRs group. However, after a 6-week recovery, all abovementioned changes mostly returned to the normal levels in the Au@AgNRs group. These indicated that after a lengthy period, acute bioeffects elicited by AgNMs could be followed by the adaptive recovery, which will provide a novel and valuable toxicity mechanism of AgNMs for potential biomedical applications of AgNMs.