Sepsis, a life‐threatening condition stemming from an uncontrolled host immune response to bacterial infections, continues to impose a significant global burden with high morbidity and mortality. ...Addressing the challenges posed by antimicrobial resistance and uncontrollable inflammation remains a challenge in sepsis treatment. Moreover, traditional antibacterial materials have low bacterial trapping efficiency and inevitable prolonged circulation within the bloodstream, resulting in suboptimal antibacterial effects, metabolic complications, and undesirable side effects. In this study, an innovative solution is introduced through the development of Fe3O4@SH@TBTCP‐PMB, an aggregation‐induced emission (AIE) photosensitizer (PS)‐armored magnetic nanoparticles (NPs). It has high reactive oxygen species (ROS) generation efficiency and an exceptional ability to capture Gram‐positive bacteria with over 80% enrichment efficiency within just 1 h, even at low bacterial concentrations. Under white light illumination, 100 µg mL−1 of Fe3O4@SH@TBTCP‐PMB effectively eliminated more than 99.9% of methicillin‐resistant Staphylococcus aureus (MRSA). Furthermore, its magnetic separation properties efficiently prevent systemic blood circulation and associated side effects. Most importantly, Fe3O4@SH@TBTCP‐PMB demonstrates superior anti‐inflammatory effects by regulating cytokines, reducing adhesion molecule expression, and managing oxidative stress levels. This multifunctional approach significantly enhances sepsis survival rates, offering a promising strategy for combating multidrug‐resistant (MDR) bacterial infections in sepsis patients while addressing inflammation‐related complications.
An aggregation‐induced emission photosensitizer‐armored magnetic nanoparticle, Fe3O4@SH@TBTCP‐PMB, that combines high ROS generation efficiency and magnetic trapping and separation character to circumvent the potential toxic side effects associated with prolonged blood circulation and metabolic challenges. It efficiently traps Gram‐positive bacteria, eliminates multidrug‐resistant bacteria, attenuates the inflammatory response, and restores the innate immune defense system to conquer sepsis in mouse model.
Neurocognitive deficits arising from anesthetic exposure have recently been debated, while studies have shown that the phosphorylation of cyclic AMP response element-binding protein (CREB) in the ...hippocampus is critical for long-term memory. To better understand the neural effects of inhalational anesthetics, we studied the behavioral and biochemical changes in aged rats that were exposed to sevoflurane (Sev) and nitrous oxide (N2O) for 4 h. Eighteen-month-old rats were randomly assigned to receive 1.3% sevoflurane and 50% nitrous oxide/50% oxygen or 50% oxygen for 4 h. Spatial learning and memory were tested with the Morris water maze 48 h after exposure, and the results showed that sevoflurane-nitrous oxide exposure induced a significant deficit in spatial learning acquisition and memory retention. Experiments revealed that the cAMP and pCREB levels in the dorsal hippocampus were decreased in rats with anesthetic exposure in comparison with control rats 48 h after anesthesia as well as 15 min after the probe trial, but there were no significant differences in CREB expression. Besides these, the current study also found the DG neurogenesis significantly decreased as well as neuronal loss and neuronal apoptosis increased in the hippocampus of rats exposed to Sev+N2O. The current study demonstrated that down-regulation of cAMP/CREB signaling, decrease of CREB-dependent neurogenesis and neuronal survival in the hippocampus contributed to the neurotoxicity and cognitive dysfunction induced by general anesthesia with sevoflurane-nitrous oxide.
Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, which seriously threatens people's physical and mental health. Coagulation is closely related to the occurrence and ...development of HCC. Whether coagulation-related genes (CRGs) can be used as prognostic markers for HCC remains to be investigated.
Firstly, we identified differentially expressed coagulation-related genes of HCC and control samples in the datasets GSE54236, GSE102079, TCGA-LIHC, and Genecards database. Then, univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis were used to determine the key CRGs and establish the coagulation-related risk score (CRRS) prognostic model in the TCGA-LIHC dataset. The predictive capability of the CRRS model was evaluated by Kaplan-Meier survival analysis and ROC analysis. External validation was performed in the ICGC-LIRI-JP dataset. Besides, combining risk score and age, gender, grade, and stage, a nomogram was constructed to quantify the survival probability. We further analyzed the correlation between risk score and functional enrichment, pathway, and tumor immune microenvironment.
We identified 5 key CRGs (FLVCR1, CENPE, LCAT, CYP2C9, and NQO1) and constructed the CRRS prognostic model. The overall survival (OS) of the high-risk group was shorter than that of the low-risk group. The AUC values for 1 -, 3 -, and 5-year OS in the TCGA dataset were 0.769, 0.691, and 0.674, respectively. The Cox analysis showed that CRRS was an independent prognostic factor for HCC. A nomogram established with risk score, age, gender, grade, and stage, has a better prognostic value for HCC patients. In the high-risk group, CD4
T cells memory resting, NK cells activated, and B cells naive were significantly lower. The expression levels of immune checkpoint genes in the high-risk group were generally higher than that in the low-risk group.
The CRRS model has reliable predictive value for the prognosis of HCC patients.
In this paper, we proposed a decentralized cooperative lane-changing decision-making framework for connected autonomous vehicles, which is composed of three modules, i.e., state prediction, candidate ...decision generation, and coordination. In other words, each connected autonomous vehicle makes cooperative lane-changing decision independently. In the state prediction module, we employed existing cooperative car-following models to predict the vehicles' future state. In the candidate decision generation module, we proposed incentive based model to generate a candidate decision. In the candidate decision coordination module, we proposed an algorithm to avoid candidate lane-changing decision that may lead to a vehicle collision or traffic deterioration to be final decision. Moreover, the effects of decentralized cooperative lane-changing decision-making framework on traffic stability, efficiency, homogeneity, and safety are investigated in a numerical simulation experiment. Some stability, efficiency, homogeneity, and safety indicators are evaluated and show the high potential of our proposed framework in traffic dynamics.
Abstract
Background
A stronger spatial clustering of cancer burden indicates stronger environmental and human behavioral effects. However, which common cancers in China have stronger spatial ...clustering and knowledge gaps regarding the environmental and human behavioral effects have yet to be investigated. This study aimed to compare the spatial clustering degree and hotspot patterns of 11 common cancers in mainland China and discuss the potential environmental and behavioral risks underlying the patterns.
Methods
Cancer incidence data recorded at 339 registries in 2014 was obtained from the “China Cancer Registry Annual Report 2017”. We calculated the spatial clustering degree of the common cancers using the global Moran’s Index and identified the hotspot patterns using the hotspot analysis.
Results
We found that esophagus, stomach and liver cancer have a significantly higher spatial clustering degree (
$$p<0.05$$
p
<
0.05
) than others. When by sex, female esophagus, male stomach, male esophagus, male liver and female lung cancer had significantly higher spatial clustering degree (
$$p<0.001$$
p
<
0.001
). The spatial clustering degree of male liver was significantly higher than that of female liver cancer (
$$p<0.001$$
p
<
0.001
), whereas the spatial clustering degree of female lung was significantly higher than that of male lung cancer (
$$p<0.001$$
p
<
0.001
). The high-risk areas of esophagus and stomach cancer were mainly in North China, Huai River Basin, Yangtze River Delta and Shaanxi Province. The hotspots for liver and male liver cancer were mainly in Southeast China and south Hunan. Hotspots of female lung cancer were mainly located in the Pearl River Delta, Shandong, North and Northeast China. The Yangtze River Delta and the Pearl River Delta were high-risk areas for multiple cancers.
Conclusions
The top highly clustered cancer types in mainland China included esophagus, stomach and liver cancer and, by sex, female esophagus, male stomach, male esophagus, male liver and female lung cancer. Among them, knowledge of their spatial patterns and environmental and behavioral risk factors is generally limited. Potential factors such as unhealthy diets, water pollution and climate factors have been suggested, and further investigation and validation are urgently needed, particularly for male liver cancer. This study identified the knowledge gap in understanding the spatial pattern of cancer burdens in China and offered insights into targeted cancer monitoring and control.
Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in ...predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.
Secondhand smoke (SHS), a common environmental exposure factor, has become a serious public health problem. Metabolic syndrome is another worldwide clinical challenge. Our study tried to determine ...the age differences in the relationship between SHS and the risk of metabolic syndrome. Studies were searched in PubMed and Web of Science from 11 November to 30 November 2018. Eighteen studies were finally included based on inclusion and exclusion criteria. The relationship between SHS and the risk indicators of metabolic syndrome was analyzed. The weighted mean difference (WMD) of fasting plasma glucose (FPG), insulin, body mass index (BMI), and waist circumference (WC), and the standard mean difference (SMD) of total cholesterol, triglycerides, and low- and high-density lipoprotein-cholesterol (LDL-C, HDL-C) were calculated in a meta-analysis. SHS was positively associated with the level of insulin and WC. According to the subgroup analysis based on age difference, SHS was positively associated with FPG in the upper age group, and positively associated with LDL-C and negatively associated with HDL-C in the lower age group. BMI showed a more obvious positive correlation in the adults group than in the children and the teenagers group. In conclusion, the association of metabolic syndrome with SHS varies with age. When exposed to SHS, older people may be more susceptible to glucose metabolic disorder, but younger people may be more susceptible to lipid metabolic disorder.
Abstract Objectives Rheumatoid arthritis (RA) is a heterogenic and systemic autoimmune disease characterized by synovitis and joint structural damage. However, the pathogenesis of RA is still ...obscure. It has been reported microRNA-20a (miRNA-20a) was significantly associated with the regulation of pro-inflammatory cytokines release in RA FLS. The purpose of this study was to explore the function and underlying mechanisms of miRNA-20a on NLRP3-inflammasome in adjuvant-induced arthritis (AA) fibroblast-like synoviocytes (FLSs) in vitro. Methods In this study, using a combination of Western blotting, Q-PCR, and ELISA analysis, we investigated the influence and function of miRNA-20a on NLRP3-inflammasome by targeting TXNIP in AA FLSs. Results In the present study, the expression of NLRP3-inflammasome was significant up-regulated in AA model in vitro. Our study indicated that silence of NLRP3 down-regulated the expression of NLRP3-inflammasome and the secretion of IL-1β and MMP-1. Moreover, over-expression of miR-20a decreased formation of NLRP3-inflammasome, including NLRP3, ASC and caspase-1, and suppressed the secretion of IL-1β and MMP-1, along with down-regulated the expressions of TXNIP in primary FLSs isolated from AA. With the combined use of prediction programs and luciferase assay, the rat TXNIP mRNA 3′UTR predicted to be targeted by miR-20a. Similarly, inhibitor TXNIP expression by TXNIP-siRNA markedly repressed formation of NLRP3-inflammasome and the secretion of IL-1β and MMP-1. Conclusion Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.
Quantitative real-time PCR (qRT-PCR) is the most classical technique in the field of gene expression study. This method requires an appropriate reference gene to normalize mRNA levels. In this study, ...the expression stability of four frequently-used reference genes in epididymal white adipose tissue (eWAT), inguinal beige adipose tissue (iBeAT) and brown adipose tissue (BAT) from obese and lean rats were evaluated by geNorm, NormFinder and BestKeeper. Based on the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, the two most stable reference genes were recommended in each type of adipose tissue. Two target genes were applied to test the stability of the reference genes. The geNorm and NormFinder results revealed that GAPDH and 36B4 exhibited the highest expression stabilities in eWAT, while 36B4 and β-actin had the highest expression stabilities in iBeAT and BAT. According to the results of the BestKeeper analysis, 36B4 was the most stable gene in eWAT, iBeAT and BAT, in terms of the coefficient of variance. In terms of the coefficient of correlation, GAPDH, 36B4 and β-actin were the most stable genes in eWAT, iBeAT and BAT, respectively. Additionally, expected results and statistical significance were obtained using a combination of two suitable reference genes for data normalization. In conclusion, 36B4 and GAPDH, in combination, are the best reference genes for eWAT, while 36B4 and β-actin are two most suitable reference genes for both iBeAT and BAT. We recommend using these reference genes accordingly.
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