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Cadmium is one of the environmental and occupational pollutants and its potential adverse effects on human health have given rise to substantial concern. Cadmium causes damage to the male reproductive system via induction of germ-cell apoptosis; however, the underlying mechanism of cadmium-induced reproductive toxicity in Leydig cells remains unclear. In this study, twenty mice were divided randomly into four groups and exposed to CdCl 2 at concentrations of 0, 0.5, 1.0 and 2.0 mg/kg/day for four consecutive weeks. Testicular injury, abnormal spermatogenesis and apoptosis of Leydig cells were observed in mice. In order to investigate the mechanism of cadmium-induced apoptosis of Leydig cells, a model of mouse Leydig cell line (i.e. TM3 cells) was subjected to treatment with various concentrations of CdCl 2 . It was found that mitochondrial function was disrupted by cadmium, which also caused a significant elevation in levels of mitochondrial superoxide and cellular ROS. Furthermore, while cadmium increased the expression of mitochondrial fission proteins (DRP1 and FIS1), it reduced the expression of mitochondrial fusion proteins (OPA1 and MFN1). This led to excessive mitochondrial fission, the release of cytochrome c and apoptosis. Conversely, cadmium-induced accumulation of mitochondrial superoxide was decreased by the inhibition of mitochondrial fission through the use of Mdivi-1 (an inhibitor of DRP1). Mdivi-1 also partially prevented the release of cytochrome c from mitochondria to cytosol and attenuated cell apoptosis. Finally, given the accumulation of LC3II and SQSTM1/p62 and the obstruction of Parkin recruitment into damaged mitochondria in TM3 cells, the autophagosome-lysosome fusion was probably inhibited by cadmium. Overall, these findings suggest that cadmium induces apoptosis of mouse Leydig cells via the induction of excessive mitochondrial fission and inhibition of mitophagy.

Background The fatty acid content represents a crucial quality trait in Brassica napus or rapeseed. Improvements in fatty acid composition markedly enhance the quality of rapeseed oil. Results Here, we perform a genome-wide association study (GWAS) to identify quantitative trait locus (QTLs) associated with fatty acid content. We identify a total of seven stable QTLs and find two loci, qFA.A08 and qFA.A09.1 , subjected to strong selection pressure. By transcriptome-wide association analysis (TWAS), we characterize 3295 genes that are significantly correlated with the composition of at least one fatty acid. To elucidate the genetic underpinnings governing fatty acid composition, we then employ a combination of GWAS, TWAS, and dynamic transcriptomic analysis during seed development, along with the POCKET algorithm. We predict six candidate genes that are associated with fatty acid composition. Experimental validation reveals that four genes ( BnaA09.PYRD , BnaA08.PSK1 , BnaA08.SWI3 , and BnaC02.LTP15 ) positively modulate oleic acid content while negatively impact erucic acid content. Comparative analysis of transcriptome profiles suggests that BnaA09.PYRD may influence fatty acid composition by regulating energy metabolism during seed development. Conclusions This study establishes a genetic framework for a better understanding of plant oil biosynthesis in addition to providing theoretical foundation and valuable genetic resources for enhancing fatty acid composition in rapeseed breeding.

Rapeseed ( Brassica napus ) is an important oilseed crop widely planted in the world, providing substantial edible oil and other nutrients for mankind. The composition of fatty acids affects the edible and processing quality of vegetable oils, among which erucic acid (EA) is potentially to cause health problems. Therefore, low erucic acid (LEA) has always been a breeding trait of B. napus . Fatty acid elongase 1 ( FAE1 ) plays a decisive role in the synthesis of EA. There are two functional homologous copies of FAE1 on the A08 and C03 chromosomes in B. napus . In this study, we used CRISPR/Cas9 technology to create targeted mutations on these two homologous copies of BnaFAE1 in three B. napus germplasms with high EA (>30%) and high oil (>50%). Our results show that the EA content was significantly reduced by more than 10 percentage points in the mutant of BnaC03.FAE1 ( c03 ), while the double mutation of BnaA08.FAE1 and BnaC03.FAE1 ( a08c03 ) resulted in nearly zero EA in three BnaFAE1- edited germplasms, and the oleic acid content was increased in different degrees. In addition, knockout of BnaA08.FAE1 or/and BnaC03.FAE1 mildly decreased seed oil content, but had no significant effect on other agronomic traits. In general, we successfully created low EA germplasms of B. napus , which provides a feasible way for future low EA breeding.

[This corrects the article DOI: 10.3389/fimmu.2025.1638156.].

ObjectiveA growing body of evidence points to a role for herpesviruses in the development of Alzheimer’s disease (AD) and a reduced risk of AD among patients receiving antiherpetic medications. We investigated the association between herpes simplex virus type 1 (HSV-1) and AD using real-world data (RWD) from USA.DesignIn a matched case–control study, patients with AD aged ≥50 years diagnosed between 2006 and 2021 were identified from the IQVIA PharMetrics Plus claims database. Controls were matched in a 1:1 ratio with subjects with AD on age, sex, region, database entry year and healthcare visit numbers.ResultsThe study included 344 628 AD case–control pairs. History of HSV-1 diagnosis was present in 1507 (0.44%) patients with AD compared with 823 (0.24%) controls. HSV-1 diagnosis was found to be associated with AD (adjusted OR 1.80; 95% CI 1.65 to 1.96). Patients with HSV-1 who used antiherpetics were less likely to develop AD compared with those who did not use antiherpetics (adjusted HR 0.83, 95% CI 0.74 to 0.92).ConclusionsFindings from this large RWD study implicate HSV-1 in the development of AD and highlight antiherpetic therapies as potentially protective for AD and related dementia.

Early diagnosis of sepsis is essential to reducing mortality. Immune cells and telomeres play important roles in sepsis, but their mechanisms were still unclear. This study aimed to explore the value of immune cells and telomere-related genes in sepsis. In this study, the transcriptomic data with sepsis and control samples were obtained from public database. Multiple methods including differential expression analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), 101-machine learning algorithm combinations were used to identify biomarkers which related to the immune cells and telomere. Afterwards, a nomogram was constructed to assess the clinical predictive value of biomarkers. In addition, gene set enrichment analysis (GSEA), regulatory network construction and drug prediction analysis were adopted to demonstrate the role of biomarkers in sepsis. The key cells were also identified using a single-cell dataset. Finally, the expression of biomarkers was further validated in clinical samples by reverse transcription quantitative polymerase chain reaction (RT-qPCR). This study obtained a total of 4 biomarkers ( , , , and ), and the analysis of nomogram showed that the biomarkers had good clinical predictive value to sepsis. The enrichment analysis results revealed that the four biomarkers were enriched in the ribosome pathway. Besides, a lncRNAs-miRNAs-biomarkers network was constructed for the four biomarkers. Finally, we obtained a candidate drug (MS-275) and a key cell (CD16+ and CD14+ monocytes) respectively based on drug prediction and cell identification analysis. In addition, we found that the expression levels of and had significant changes during the process of key cell differentiation. The RT-qPCR results showed biomarkers were upregulated in the sepsis group, consistent with the bioinformatics analysis results. This study identified 4 biomarkers, namely , , , and and explored the pathogenesis of sepsis, providing new insights for potential treatment strategies by integrating transcriptomic data and single-cell analysis.

Pseudorabies virus (PRV), a swine alphaherpesvirus, is a double-stranded DNA virus. It may infect various animals, especially pigs. PRV infection in pigs leads to high mortality rates, and causes huge economic lose for swine industry. Currently, there are few effective antiviral treatments available. Rosmarinic acid (RA), a hydrophilic phenolic compound, shows potential for inhibiting herpes simplex virus. Given that PRV is a member of the Herpesviridae family, this study investigated the antiviral effects of RA against PRV infection through both in vitro and in vivo, as well as the underlying molecular mechanisms. PK-15 cells were used to assess the cytotoxicity of RA in vitro, followed by an investigation of its anti-PRV activity. The study then explored how RA regulates the cGAS-STING signaling pathway, along with inflammatory and apoptotic factors in PRV-infected cells. Molecular docking and dynamics simulations further elucidated the binding interactions between RA and cGAS-STING, providing insight into how RA activates the cGAS-STING pathway against PRV infection. In vivo, the antiviral efficacy of RA was evaluated in a PRV-infected mouse model by assessing tissue viral genome copies, the innate immune cGAS-STING signaling pathway activation, and inflammatory and apoptotic responses. The results showed that RA exhibited a half-maximal cytotoxic concentration (CC 50 ) of 26.23 µg/mL on PK-15 cells and a half-maximal inhibitory concentration (IC 50 ) of 0.84 µg/mL against PRV, resulting in a selectivity index (SI) of 31.22. These findings suggest that RA is a highly effective and low-toxicity compound. RA significantly inhibited PRV adsorption, penetration, and replication within cells. Additionally, while PRV infection suppresses the cGAS-STING signaling pathway, RA treatment activates the innate immune response, enhances downstream antiviral effector IFN-β expression, and reduces inflammation and apoptosis in PRV-infected cells. Molecular docking results showed that the docking scores of cGAS_RA and STING_RA complexes were both less than − 5 kcal/mol, suggesting that RA binds well to cGAS and STING proteins. Molecular dynamics simulations, including RMSD, RMSF, and MM-GBSA analyses, confirmed the high binding stability of cGAS with RA, further validating the potential activity of RA as a cGAS agonist. In vivo studies revealed that RA dramatically lowered viral genome copies in various organs, activated the cGAS-STING signaling pathway, inhibited PRV-induced inflammation and apoptosis, alleviated clinical symptoms, and decreased mortality rate in PRV-infected mice. Overall, RA significantly inhibited PRV proliferation in vitro and in vivo, effectively reduced inflammation and apoptosis, and decreased the mortality rate in infected mice. The study supports the development of RA as an antiviral drug and emphasizes its potential as a candidate for PRV therapy.

The recent availability of digital traces generated by cellphone calls has significantly increased the scientific understanding of human mobility. Until now, however, based on low time resolution measurements, previous works have ignored to study human mobility under various time scales due to sparse and irregular calls, particularly in the era of mobile Internet. In this paper, we introduced Mobile Flow Records, flow-level data access records of online activity of smartphone users, to explore human mobility. Mobile Flow Records collect high-resolution information of large populations. By exploiting this kind of data, we show the models and statistics of human mobility at a large-scale (3,542,235 individuals) and finer-granularity (7.5min). Next, we investigated statistical variations and biases of mobility models caused by different time scales (from 7.5min to 32h), and found that the time scale does influence the mobility model, which indicates a deep coupling of human mobility and time. We further show that mobility behaviors like transportation modes contribute to the diversity of human mobility, by exploring several novel and refined features (e.g., motion speed, duration, and trajectory distance). Particularly, we point out that 2-hour sampling adopted in previous works is insufficient to study detailed motion behaviors. Our work not only offers a macroscopic and microscopic view of spatial-temporal human mobility, but also applies previously unavailable features, both of which are beneficial to the studies on phenomena driven by human mobility.

Long-term sequelae of COVID-19 remain critical public health concerns, with limited therapeutic options available. We conducted two case-control studies among COVID-19 infected individuals in the UK Biobank to explore the association of sociodemographic factors, clinical biomarkers, and comorbidities with the risk of two key phenotypes: Long COVID (LC, defined by patient self-report symptoms) and post-acute complications of SARS-CoV-2 infection (PACS, defined by clinical diagnosis), separately. Our study included 8,668 participants in the LC cohort (32% classified as cases) and 108,407 in the PACS cohort (with 2% being cases). Findings showed that age and sex were associated with both LC and PACS but in opposite directions. Additionally, obesity, socioeconomic deprivation, elevated C-reactive protein, triglyceride, vitamin D, HbA1c, cystatin C, urate, and alanine aminotransferase, and decreased HDL cholesterol and IGF-1, as well as CKD and COPD, were associated with LC. Most of these factors were also significant for PACS, except for alanine aminotransferase and vitamin D. These findings have potential mechanistic implications for the distinction between LC and PACS and can guide clinical implementation of identifying high-risk groups for targeted vaccination or other public health mitigation strategies. Long-term consequences of COVID-19 can be identified by patient reported symptoms (long COVID) or clinical diagnosis (post-acute complications of SARS-CoV-2). Here, the authors perform two case control studies using data from UK Biobank to investigate risk factors for both outcomes.

When biochars are produced, feedstock is a crucial factor that determines their physicochemical properties. However, the characteristics of tropical crop waste-derived biochar have not been described and limit its availability. In this study, pineapple leaf (PAL), banana stem (BAS), sugarcane bagasse (SCB) and horticultural substrate (HCS), were used to prepare biochar at 300, 500 and 700 °C. Properties of biochars and their applications were analysed. The results indicated that hydrophobicity, nonpolarity and aromaticity of SCB biochar (SCBB) were higher than other biochars due to the loss of H (hydrogen), O (oxygen), and N (nitrogen). The pH of PAL biochar (PALB) and BAS biochar (BASB) ranged from 9.69 to 10.30 higher than that of SCBB and HCS biochar (HCSB) with 7.17–9.77. In PALB and BASB, sylvite was the dominant crystal structure. With temperature rising, C–H stretching, C=C stretching and H–O in alcohol groups decreased, and Si–O stretching in HCSB and SCBB strengthened. Biochars obtained at 500 °C, especially SCBB and HCSB, significantly promoted the growth of maize. The PALB and BASB greatly increased the soil pH/EC to 6.90–7.35 and 0.67–0.95 ms/cm, while those of SCBB and HCSB were 5.97–6.74 and 0.23–0.45 ms/cm. The application of the biochars to the soil increased soil pH, reducing the acidic soil stress in maize growth, especially PAL and BAS biochars prepared at 300 °C. Biochar prepared at lower temperature will greatly reduce energy consumption and increase the utilization efficiency of tropical agricultural waste resources.