Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line.

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer's disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

Screening of key immune-related gene in Parkinson's disease based on WGCNA and machine learning. / 基于WGCNAå’Œæœºå™¨å­¦ä¹ ç­›é€‰å¸•é‡‘æ£®ç— å ç–«ç›¸å ³å ³é”®åŸºå› .

OBJECTIVES: Abnormal immune system activation and inflammation are crucial in causing Parkinson's disease. However, we still don't fully understand how certain immune-related genes contribute to the disease's development and progression. This study aims to screen key immune-related gene in Parkinson's disease based on weighted gene co-expression network analysis (WGCNA) and machine learning. METHODS: This study downloaded the gene chip data from the Gene Expression Omnibus (GEO) database, and used WGCNA to screen out important gene modules related to Parkinson's disease. Genes from important modules were exported and a Venn diagram of important Parkinson's disease-related genes and immune-related genes was drawn to screen out immune related genes of Parkinson's disease. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the the functions of immune-related genes and signaling pathways involved. Immune cell infiltration analysis was performed using the CIBERSORT package of R language. Using bioinformatics method and 3 machine learning methods [least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and support vector machine (SVM)], the immune-related genes of Parkinson's disease were further screened. A Venn diagram of differentially expressed genes screened using the 4 methods was drawn with the intersection gene being hub nodes (hub) gene. The downstream proteins of the Parkinson's disease hub gene was identified through the STRING database and a protein-protein interaction network diagram was drawn. RESULTS: A total of 218 immune genes related to Parkinson's disease were identified, including 45 upregulated genes and 50 downregulated genes. Enrichment analysis showed that the 218 genes were mainly enriched in immune system response to foreign substances and viral infection pathways. The results of immune infiltration analysis showed that the infiltration percentages of CD4+ T cells, NK cells, CD8+ T cells, and B cells were higher in the samples of Parkinson's disease patients, while resting NK cells and resting CD4+ T cells were significantly infiltrated in the samples of Parkinson's disease patients. ANK1 was screened out as the hub gene. The analysis of the protein-protein interaction network showed that the ANK1 translated and expressed 11 proteins which mainly participated in functions such as signal transduction, iron homeostasis regulation, and immune system activation. CONCLUSIONS: This study identifies the Parkinson's disease immune-related key gene ANK1 via WGCNA and machine learning methods, suggesting its potential as a candidate therapeutic target for Parkinson's disease.

Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy.

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.

Crosstalk of non-apoptotic RCD panel in hepatocellular carcinoma reveals the prognostic and therapeutic optimization.

Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients' tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.

Lipoproteins and metabolites in diagnosing and predicting Alzheimer's disease using machine learning.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD. METHODS: A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer's disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants' age, sex, and marital status, were used to construct a random forest predictive model. RESULTS: Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with "mtry" set to 3 and "ntree" set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645-0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables. CONCLUSIONS: Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.

Mendelian randomization study on causal association of FAM210B with drug-induced lupus.

OBJECTIVE: Due to the complexity of drug-induced lupus (DIL) pathogenesis, more susceptibility factors need to be discovered. FAM210B is a new mitochondrial protein whose function has not been fully elucidated. This study will explore whether there is a correlation between FAM210B and the risk of DIL. METHODS: At first, we extracted three FAM210B genetic variants from the GTEx database (n = 948), and extracted their corresponding genome-wide association study (GWAS) summary statistics from DIL (101 DIL cases and 218691 controls). Then, we performed a Mendelian randomization (MR) study to evaluate the causal association of the expression of FAM210B with DIL using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test. RESULTS: We successfully extracted three FAM210B single-nucleotide polymorphisms (SNPs) (rs116032784, rs34361943 and rs33923703) from the GTEx_Analysis_v8_eQTL data that can reduce FAM210B expression. The results of the MR analysis showed that genetically reduced expression of FAM210B was significantly associated with increased risk of DIL in European ancestry based on the IVW method (ß = 1.037, p = 0.001, odds ratio [OR] = 2.821, 95% confidence interval [CI]:1.495-5.322). CONCLUSION: MR analysis showed a causal relationship between FAM210B expression and the risk of DIL disease. Our results suggested that FAM210B may be a marker that can mark susceptibility of DIL in the future. It provides evidence for the study of DIL, but its specific mechanism of action in DIL needs to be further studied. Key Points •This is the first MR analysis to examine the association between FAM210B and DIL. •The findings of this study suggested that reduced FAM210B expression is associated with the increased risk of DIL. •FAM210B may be a marker that can mark susceptibility of DIL in the future.

Toxicological effects and mechanisms of lithium on growth, photosynthesis and antioxidant system in the freshwater microalga Chromochloris zofingiensis.

The growing prevalence of lithium (Li) batteries has drawn public attention to Li as an emerging pollutant. The present study investigates the toxicity of Li+ on Chromochloris zofingiensis, examining physiological, biochemical and omics aspects. Results reveal hormesis effects of Li+ on C. zofingiensis growth. At Li+ concentrations below 5 mg L-1, Li+ can enhance chlorophyll content, mitochondrial activity, and antioxidant capacity, leading to increased dry cell weight and cell number. Conversely, when it exceeded 10 mg L-1, Li+ can reduce chlorophyll content, induce oxidative stress, and disrupt chloroplast and mitochondria structure and function, ultimately impeding cell growth. In addition, under 50 mg L-1 Li+ stress, microalgae optimize absorbed light energy use (increasing Fv/Fm and E TR ) and respond to stress by up-regulating genes in starch and lipid biosynthesis pathways, promoting the accumulation of storage components. Weighted gene co-expression network analysis indicates that peptidylprolyl cis/trans isomerase, GTPase and L-ascorbate oxidase might be the key regulators in response to Li+ stress. This research marks the toxic effects and molecular mechanisms of Li+ on freshwater microalga, which would improve our understanding of Li's toxicology and contributing to the establishment of Li pollution standards.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

Next-Generation Preclinical Functional Testing Models in Cancer Precision Medicine: CTC-Derived Organoids.

Basic and clinical cancer research requires tumor models that consistently recapitulate the characteristics of prima tumors. As ex vivo 3D cultures of patient tumor cells, patient-derived tumor organoids possess the biological properties of primary tumors and are therefore excellent preclinical models for cancer research. Patient-derived organoids can be established using primary tumor tissues, peripheral blood, pleural fluid, ascites, and other samples containing tumor cells. Circulating tumor cells acquired by non-invasive sampling feature dynamic circulation and high heterogeneity. Circulating tumor cell-derived organoids are prospective tools for the dynamic monitoring of tumor mutation evolution profiles because they reflect the heterogeneity of the original tumors to a certain extent. This review discusses the advantages and applications of patient-derived organoids. Meanwhile, this work highlights the biological functions of circulating tumor cells, the latest advancement in research of circulating tumor cell-derived organoids, and potential application and challenges of this technology.

Sex-specific effects of organophosphate ester exposure on child growth trajectories in the first two years.

The connections between urinary organophosphate ester (OPE) metabolites and child growth have been identified in prior research, but there is currently a dearth of epidemiological evidence regarding the sex-specific impact of OPEs on child growth trajectories. This study enrolled 804 maternal-child pairs, and five OPE congeners were quantified in maternal serum during pregnancy. In this study, the impact of prenatal OPE exposure on child growth trajectories was assessed using linear mixed-effect models and a group-based trajectory model (GBTM), with consideration given to sex-specific effects. Fetuses were frequently exposed to OPEs in utero, and tris(2-butoxyethel) phosphate (TBEP) exhibited the highest concentration levels in maternal serum. Among male children, an increase of 2.72 ng/g lipid in TBEP concentration was associated with a 0.11-unit increase in head circumference-for-age z-score (HCAZ), and the effect was mainly concentrated at 1 and 2 months of age. Among female children, an increase of 2.72 ng/g lipid in tris(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) concentration was associated with a 0.15-unit increase in length-for-age z-score (LAZ) and a 0.14-unit increase in weight-for-age z-score (WAZ), and the effects were mainly concentrated at 9 months of age. For HCAZ trajectories, higher prenatal TBEP exposure was associated with higher odds for the fast growth group in male children. For the LAZ and WAZ trajectories, higher prenatal TDCPP exposure was associated with higher odds for the fast growth group in female children. The trajectory analysis approach provided insight into the complex associations between OPE exposure and child growth.

Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats.

Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococcaceae may contribute to the alteration in serum L-carnitine and trigonelline, leading to hepatic lipid accumulation following CP exposure. Additionally, Ruminococcaceae, Lachnospiraceae, and Porphyromonadaceae were associated with CP-induced glutamatergic hypofunction and overproduction of TNF-α, potentially contributing to the brain neurotoxicity. Overall, the study provides important insights into the potential mechanisms underlying CP-induced toxicity and highlights the need for continued research to fully understand the implications for CP-induced health risks. The incorporation of the gut-organ axis theory in the study provides a promising avenue for future research into the potential interactions between gut microbiota and organ toxicity, and the potential for targeted interventions to mitigate the adverse effects of environmental toxins.

Process-based dynamic identification indicators of soybean chilling damage and analysis of the corresponding spatiotemporal characteristics in Northeast China.

Northeast China (NEC) is one of the main soybean-producing areas among the northern-latitude regions. Climate warming leads to frequent extreme disasters, and the threat of chilling damage to soybean production in NEC cannot be ignored. The study aimed to construct a dynamic disaster identification index based on the static evaluation of soybean after the disaster, taking into account the process of soybean chilling damage and using the historical disaster records to realize the dynamic prediction and analysis before the disaster. Taking soybean in NEC as the research object, chilling damage indicators of soybeans in NEC were constructed by dividing the mature regions, using daily temperature anomaly and negative temperature anomaly day data with the comprehensive consideration of the chilling damage intensity, duration, and temperature recovery. The results showed that the comprehensive indicators determined by the cumulative value of temperature anomaly-the cumulative days of negative temperature anomaly had better applicability in NEC than the single factor indicator. The indicator results were basically consistent with the historical disaster records, and the accuracy rate of the indicator verification reached 90.9%. Based on the analysis of the constructed indicators, the frequency of delayed chilling damage in NEC showed a fluctuating downward trend from 1961 to 2020. The station ratio of delayed chilling damage in NEC showed a fluctuating downward trend, with the most obvious downward trend occurring for severe damage, followed by moderate damage, and the least obvious trend observed for light damage. The scope of chilling damage gradually narrowed, with the frequency increasing from southeast to northwest. The high-risk areas of chilling damage were concentrated mainly in the northern part of Heilongjiang Province and the East Four Leagues. The risk of chilling damage in most areas of Jilin Province and Liaoning Province was relatively low. The study results provide basic support for the risk research of soybean chilling damage and for ensuring disaster monitoring and early warnings, and the risk assessment based on the chilling damage process has positive significance for adjusting agricultural structure and improving the distribution of soybean varieties.

The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer.

BACKGROUND: Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. METHODS: Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. RESULTS: Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. CONCLUSIONS: PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients.

Mendelian randomization study on causal association of IL-6 signaling with pulmonary arterial hypertension.

BACKGROUND: A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. METHODS: Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. RESULTS: We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013-0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024-0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16-1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10-1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05-1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12-1.63; p = .0035). CONCLUSION: Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH.

Dynamic gene screening enabled identification of a 10-gene panel for early detection and progression assessment of gastric cancer.

Early diagnosis and progression assessment are critical for the timely detection and treatment of gastric cancer (GC) patients. Identification of diagnostic biomarkers for early detection of GC represents an unmet clinical need, and how these markers further influence GC progression is explored rarely. We performed dynamic gene screening based on high-throughput data analysis from patients with precancerous lesions and early gastric cancer (EGC) and identified a 10-gene panel by the lasso regression model. This panel demonstrated good diagnostic performance in TCGA (AUC = 0.95, sensitivity = 86.67 %, specificity = 90.63 %) and GEO (AUC = 0.84, sensitivity = 91.67 %, specificity = 78.13 %) cohorts. Moreover, three GC subtypes were clustered based on this panel, in which cluster 2 (C2) demonstrated the highest tumor progression level with a high expression of 10 genes, showing a decreased tumor mutation burden, significantly enriched epithelial-mesenchymal transition hallmark and increased immune exclusion/exhausted features. Finally, the cell localization of these panel genes was explored in scRNA-seq data based on more than 40,000 cells. The 10-gene panel is expected to be a new clinical early detection signature for GC and may aid in progression assessment and personalized treatment of patients.

Mendelian randomization study on the causal effect of chickenpox on dementia.

Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome-wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two-sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse-variance weighted analysis (ß = 0.070, 95% confidence interval [CI] for ß: 0.014-0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015-1.134; p = 0.014) and weighted median (ß = 0.071, 95% CI for ß: 0.002-0.141; OR = 1.074, 95% CI for OR: 1.002-1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia.

Chickenpox and multiple sclerosis: A Mendelian randomization study.

Observational studies have suggested a suspected association between varicella-zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS. We performed a two-sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome-wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107 769 cases and 15 982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14 802 MS cases and 26 703 controls. We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27, 95% confidence interval [CI] = 22.97-54.17, p = 1.46E-59). Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention.

Older Adults Show Intraindividual Variation in the Use of Predictive Processing.

BACKGROUND: The use of prediction can aid language comprehension through preactivation of relevant word features. However, predictions can be wrong, and it has been proposed that resolving the mismatch between the predicted and presented item requires cognitive resources. Older adults tend not to predict and instead rely more on passive comprehension. Here, we tested, using an intraindividual approach, whether older adults consistently use this less demanding processing strategy while reading or whether they attempt to predict on some trials. METHODS: We used a cross-task conflict paradigm. Younger and older participants self-paced to read sentences that ended with either an expected or unexpected word. Each sentence was then followed by a flanker stimulus that could be congruent or incongruent. We examined responses within and across the two tasks. RESULTS: Unexpected words were in general read as quickly as expected words, indicating that typical processing of these words was similar. However, for both younger and older adults, there was a greater proportion of very slow trials for unexpected words, revealing different processing on a subset of trials. Critically, in older adults, these slowly read unexpected words engaged control, as seen in speeded responses to incongruent flanker stimuli. CONCLUSION: Using a cross-task conflict paradigm, we showed that older adults are able to predict and engage cognitive resources to cope with prediction violations, but do not opt to use these processes consistently.

Soil Storage Conditions Alter the Effects of Tire Wear Particles on Microbial Activities in Laboratory Tests.

In this study, we focused on the fact that soil storage conditions in the laboratory have never been considered as a key factor potentially leading to high variation when measuring effects of microplastics on soil microbial activity. We stored field-collected soils under four different conditions [room-temperature storage, low-temperature storage (LS), air drying (AD), and heat drying] prior to the experiment. Each soil was treated with tire wear particles (TWPs), and soil microbial activities and water aggregate stability were investigated after soil incubation. As a result, microbial activities, including soil respiration and three enzyme activities (ß-glucosidase, N-acetyl-ß-glucosaminidase, and phosphatase), were shown to depend on soil storage conditions. Soil respiration rates increased with the addition of TWPs, and the differences from the control group (no TWPs added) were more pronounced in the AD TWP treatment than in soils stored under other conditions. In contrast, phosphatase activity followed an opposing trend after the addition of TWPs. The AD soil had higher phosphatase activity after the addition of TWPs, while the LS soil had a lower level than the control group. We suggest that microplastic effects in laboratory experiments can strongly depend on soil storage conditions.

New separation protocol reveals spray painting as a neglected source of microplastics in soils.

Microplastics are recently discovered contaminants, yet knowledge on their sources and analysis is limited. For instance, paint microplastics are poorly known because soil separation protocols using flotation solutions cannot separate paint microplastics due to the higher density of paint microplastic versus common microplastics. Here, we designed a new two-step density separation protocol for paint microplastics, allowing paint microplastics to be separated from the soil without digestion. Paint particles were separated from soil samples collected around the graffiti wall at the Mauerpark, Berlin, then quantified according to their shape and color characteristic. The presence of polymers as binders in the paint particles was verified by Fourier transform infrared spectroscopy. Results show concentrations from 1.1 × 105 to 2.9 × 105 microplastics per Kg of dry soil, representing the highest microplastic concentration ever reported in the literature. Particle concentrations decreased and the median size increased with soil depth. Our results provide first evidence that spray painting, a technique with a wide range of applications from industry to art, leaves a legacy of environmental microplastic in soils that has so far gone unnoticed. Supplementary Information: The online version contains supplementary material available at 10.1007/s10311-022-01500-2.