Low-cost and sensitive chemiluminescence detection of phthalates in environment by signal sensing of carbon-based materials from PVC/coal gangue dechlorination.

BACKGROUND: The detection of plasticizers in the environment is important to prevent environmental risks and people's health hazards. Improving recycling efficiency of waste PVC still faced challenges. RESULTS: In this work, it was found that solid products from waste PVC/coal gangue dechlorination in subcritical water (dPVC) had strong catalysis activity for luminol-H2O2 chemiluminescence (CL) reaction. Phthalates, common plasticizers, could bond and adsorb on dPVC, which greatly inhibited the luminol-H2O2-dPVC CL reaction. Based on this, a low-cost CL analysis was constructed for the detection of phthalates combinations (PACs) and di-(2-ethylhexyl) phthalate (DEHP) in the environment. The detection limit for PACs and DEHP was 0.048 ng/L and 0.13 ng/L, respectively. Compared with HPLC standard method, the dPVC CL analysis had accuracy and reliability for the detection of phthalates in actual environmental samples. Besides, the results of life cycle assessment (LCA) revealed that dPVC for CL sensing materials had significantly small global warming potential (GWP). SIGNIFICANCE: The use of dPVC for CL sensing not only improved the recycling efficiency of PVC, but also reduced carbon emissions of obtaining CL sensing materials.

Mapping and functional characterization of structural variation in 1060 pig genomes.

BACKGROUND: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. RESULTS: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. CONCLUSIONS: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.

A new approach towards highly sensitive detection of endogenous N-acetylaspartic acid, N-acetylglutamic acid, and N-acetylaspartylglutamic acid in brain tissues based on strong anion exchange monolith microextraction coupled with UHPLC-MS/MS.

A novel in-tube solid-phase microextraction coupled with an ultra-high performance liquid chromatography-mass spectrometry method has been established for simultaneous quantification of three crucial brain biomarkers N-acetylaspartic acid (NAA), N-acetylglutamic acid (NAG), and N-acetylaspartylglutamic acid (NAAG). A polymer monolith with quaternary ammonium as the functional group was designed and exhibited efficient enrichment of target analytes through strong anion exchange interaction. Under the optimized conditions, the proposed method displayed wide linear ranges (0.1-80 nM for NAA and NAG, 0.2-160 nM for NAAG) with good precision (RSDs were lower than 15%) and low limits of detection (0.019-0.052 nM), which is by far the most sensitive approach for NAA, NAG, and NAAG determination. Furthermore, this approach has been applied to measure the target analytes in mouse brain samples, and endogenous NAA, NAG, and NAAG were successfully detected and quantified from only around 5 mg of cerebral cortex, cerebellum, and hippocampus. Compared with existing methods, the newly developed method in the current study provides highest sensitivity and lowest sample consumption for NAA, NAG, and NAAG measurements, which would potentially be utilized in determining and tracking these meaningful brain biomarkers in diseases or treatment processes, benefiting the investigations of pathophysiology and treatment of brain disorders.

The competition of heavy metals between hyporheic sediments and microplastics of driving factors in the Beiluo River Basin.

Both sediments and microplastics (MPs) are medias of heavy metals (HMs) in river ecosystems. This study investigated HMs (Mn, Cr, V, As, Cu, Co, Cd, Pb, and Ni) concentration and driving factors for competitive enrichment between hyporheic sediments versus MPs. The medias basic characteristics indicated that the sediments were mostly sand and rich in Fe2O3; three polymer types were identified, with blue, fragment, less than 500 µm being the main types of MPs. The results have shown that the average content of extracted HMs in MPs was much higher than that of the same metals accumulated in sediments. HMs in sediments and MPs reached heavily polluted at some points, among which As and Cd were ecological risks. Electrostatic adsorption and surface complexation, and biofilm-mediated and organic matter complexation were the interaction mechanism of HMs with sediments and MPs. Further, the driving factors affecting the distribution of HMs in the two carriers were analyzed by multivariate statistical analysis. The results demonstrated that carrier characteristics, hydrochemical factors, and the inherent metal load of MPs were the main causes of the high HMs content. These findings improved our understanding of HMs fate and environmental risks across multiple medias.

Simultaneous blastic plasmacytoid dendritic cell neoplasm and myelofibrosis: A case report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare and aggressive tumor with an unknown pathogenesis. Myelofibrosis (MF) is a type of myeloproliferative neoplasm. MF can be secondary to several hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndrome and hairy cell leukemia. In the present report, a rare case of BPDCN secondary to MF is described. A 70-year-old male patient developed a large purplish-red rash with recurrent symptoms. BPDCN was confirmed by immunohistochemistry of a biopsy specimen and flow cytometry of bone marrow cells. Bone marrow histopathology revealed MF. Next-generation sequencing of peripheral blood revealed mutations in the Tet methylcytosine dioxygenase 2 and NRAS proto-oncogene GTPase genes. The patient underwent one cycle of chemoimmunotherapy, but the condition progressed, an infection developed and the patient eventually died. The present case suggests that BPDCN can occur in conjunction with MF and that the prognosis of such patients is poor. Pathological examination and genetic testing aided in the diagnosis and treatment. This case emphasizes the need to raise awareness of BPDCN among clinicians and to be alert to the potential for fatal infection in patients with BPDCN combined with MF following myelosuppression triggered during chemotherapy.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

Exploring the Structural Plasticity Mechanism of Corticospinal Tract during Stroke Rehabilitation Based Automated Fiber Quantification Tractography.

BACKGROUND: Corticospinal tract (CST) is the principal motor pathway; we aim to explore the structural plasticity mechanism in CST during stroke rehabilitation. METHODS: A total of 25 patients underwent diffusion tensor imaging before rehabilitation (T1), 1-month post-rehabilitation (T2), 2 months post-rehabilitation (T3), and 1-year post-discharge (T4). The CST was segmented, and fractional anisotropy (FA), axial diffusion (AD), mean diffusivity (MD), and radial diffusivity (RD) were determined using automated fiber quantification tractography. Baseline level of laterality index (LI) and motor function for correlation analysis. RESULTS: The FA values of all segments in the ipsilesional CST (IL-CST) were lower compared with normal CST. Repeated measures analysis of variance showed time-related effects on FA, AD, and MD of the IL-CST, and there were similar dynamic trends in these 3 parameters. At T1, FA, AD, and MD values of the mid-upper segments of IL-CST (around the core lesions) were the lowest; at T2 and T3, values for the mid-lower segments were lower than those at T1, while the values for the mid-upper segments gradually increased; at T4, the values for almost entire IL-CST were higher than before. The highest LI was observed at T2, with a predominance in contralesional CST. The LIs for the FA and AD at T1 were positively correlated with the change rate of motor function. CONCLUSIONS: IL-CST showed aggravation followed by improvement from around the lesion to the distal end. Balance of interhemispheric CST may be closely related to motor function, and LIs for FA and AD may have predictive value for mild-to-moderate stroke rehabilitation. Clinical Trial Registration. URL: http://www.chictr.org.cn; Unique Identifier: ChiCTR1800019474.

Adipose-derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis.

Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.

DiffGAN: An adversarial diffusion model with local transformer for MRI reconstruction.

Magnetic resonance imaging (MRI) is non-invasive and crucial for clinical diagnosis, but it has long acquisition time and aliasing artifacts. Accelerated imaging techniques can effectively reduce the scanning time of MRI, thereby decreasing the anxiety and discomfort of patients. Vision Transformer (ViT) based methods have greatly improved MRI image reconstruction, but their computational complexity and memory requirements for the self-attention mechanism grow quadratically with image resolution, which limits their use for high resolution images. In addition, the current generative adversarial networks in MRI reconstruction are difficult to train stably. To address these problems, we propose a Local Vision Transformer (LVT) based adversarial Diffusion model (Diff-GAN) for accelerating MRI reconstruction. We employ a generative adversarial network (GAN) as the reverse diffusion model to enable large diffusion steps. In the forward diffusion module, we use a diffusion process to generate Gaussian mixture distribution noise, which mitigates the gradient vanishing issue in GAN training. This network leverages the LVT module with the local self-attention, which can capture high-quality local features and detailed information. We evaluate our method on four datasets: IXI, MICCAI 2013, MRNet and FastMRI, and demonstrate that Diff-GAN can outperform several state-of-the-art GAN-based methods for MRI reconstruction.

Evaluating multifaceted effects of watershed properties and human activities on drought propagation in the Wei River Basin with an integrated framework.

Understanding the factors driving propagation from meteorological to hydrological drought is crucial for drought mitigation. In this study, an integrated framework based on the Soil and Water Assessment Tool model, standardised drought indices and Geographical Detector were used to investigate how and to what extent watershed properties and human activities affect the spatial heterogeneity of drought propagation in the Wei River Basin, a typical arid and semi-arid region in China. Results indicated that (1) spatially, the propagation times increased from southwest to northeast. Seasonally, the propagation was shorter and stronger in summer and autumn. (2) The aridity index significantly affected the spatial distribution of drought propagation time for the entire basin, especially in summer, while human activities primarily drove spatial distribution in the sub-basins. The explanatory power of any two independent factors was non-linearly enhanced after the interaction. (3) Watershed properties potentially impacted the anthropogenic driving factor of drought propagation. Strong anthropogenic effects on drought propagation often occurred in watersheds with moderate drought levels, steep slopes, low elevations, and small areas, and the key factors varied seasonally. These findings help elucidate the multifaceted effects of watershed properties and human activities on drought propagation. The proposed framework and the results of this study provide valuable guidance for formulating precise drought control strategies in the Wei River Basin and worldwide.

The impact of smoking and alcohol consumption on rosacea: a multivariable Mendelian randomization study.

Backgrounds: Observational studies have shown that cigarette smoking is inversely associated with risk of rosacea, However, it remains uncertain whether this association is causal or it is a result of reverse causation, and whether this association is affected by drinking behaviors. Methods: This study utilized the summary-level data from the largest genome-wide association study (GWAS) for smoking, alcohol consumption, and rosacea. The objective was to investigate the effect of genetically predicted exposures to smoking and alcohol consumption on the risk of developing rosacea. Two-sample bidirectional Mendelian randomization (MR) was applied, accompanied by sensitive analyses to validate the robustness of findings. Furthermore, multivariable MR was conducted to evaluate the direct impact of smoking on rosacea. Results: A decreased risk of rosacea was observed in individuals with genetically predicted lifetime smoking [odds ratio (OR)MR - IVW = 0.53; 95% confidence interval (CI), 0.318-0.897; P = 0.017], and number of cigarettes per day (ORMR - IVW = 0.55; 95% CI, 0.358-0.845; P = 0.006). However, no significant associations were found between initiation of regular smoking, smoking cessation, smoking initiation, alcohol consumption and rosacea. Reverse MR analysis did not show any associations between genetic liability toward rosacea and smoking or alcohol drinking. Importantly, the effect of lifetime smoking and the number of cigarettes per day on rosacea remained significant even after adjusting for alcohol consumption in multivariable MR analysis. Conclusion: Smoking was causally related to a lower risk of rosacea, while alcohol consumption does not appear to be associated with risk of rosacea.

Nonmetallic graphite for tumor magnetic hyperthermia therapy.

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.

Bioinspired BSA@polydopamine@Fe Nanoprobe with Self-Purification Capacity for Targeted Magnetic Resonance Imaging of Acute Kidney Injury.

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.

Magnetic Resonance Angiography with Hour-Scale Duration after Single Low-Dose Administration of Biocompatible Gadolinium Oxide Nanoprobe.

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15 mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.

One-Minute Preparation of Iron Foam-Drug Implant for Ultralow-Power Magnetic Hyperthermia-Based Combination Therapy of Tumors in Vivo.

The magnetic hyperthermia-based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)-drug implant is established in an ultra-facile and universal way for ultralow-power MHCT of tumors in vivo for the first time. The IF-drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra-high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via "capillary action". In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large-scale preparation of IF-drug implants for biological application. As a proof of concept, IF-doxorubicin (IF-DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF-drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow-power combination therapy.

Enhanced gene transfection and induction of apoptosis in melanoma cells by branched poly(ß-amino ester)s with uniformly distributed branching units.

Melanoma, one of the most devastating forms of skin cancer, currently lacks effective clinical treatments. Delivery of functional genes to modulate specific protein expression to induce melanoma cell apoptosis could be a promising therapeutic approach. However, transfecting melanoma cells using non-viral methods, particularly with cationic polymers, presents significant challenges. In this study, we synthesized three branched poly(ß-amino ester)s (HPAEs) with evenly distributed branching units but varying space lengths through a two-step "oligomer combination" strategy. The unique topological structure enables HPAEs to condense DNA to form nano-sized polyplexes with favorable physiochemical properties. Notably, HPAEs, especially HPAE-2 with intermediate branching unit space length, demonstrated significantly higher gene transfection efficiency than the leading commercial gene transfection reagent, jetPRIME, in human melanoma cells. Furthermore, HPAE-2 efficiently delivered the Bax-encoding plasmid into melanoma cells, leading to a pronounced pro-apoptotic effect without causing noticeable cytotoxicity. This study establishes a potent non-viral platform for gene transfection of melanoma cells by harnessing the distribution of branching units, paving the way for potential clinical applications of gene therapy in melanoma treatment.

AT1R autoantibody promotes phenotypic transition of smooth muscle cells by activating AT1R-OAS2.

Phenotypic transition of vascular smooth muscle cells (VSMCs) is an early event in the onset and progression of several cardiovascular diseases. As an important mediator of the renin-angiotensin system (RAS), activation of the angiotensin II type 1 receptor (AT1R) induces phenotypic transition of VSMCs. AT1R autoantibodies (AT1-AAs), which are agonistic autoantibodies of AT1R, have been detected in the sera of patients with a variety of cardiovascular diseases associated with phenotypic transition. However, the effect of AT1-AA on phenotypic transition is currently unknown. In this study, AT1-AA-positive rat model was established by active immunization to detect markers of VSMCs phenotypic transition. The results showed that AT1-AA-positive rats showed phenotypic transition of VSMCs, which was evidenced by the decrease of contractile markers, while the increase of synthetic markers in the thoracic aorta. However, in AT1-AA-positive AT1R knockout rats, the phenotypic transition-related proteins were not altered. In vitro, after stimulating human aortic smooth muscle cells with AT1-AA for 48 h, 2'-5' oligoadenylate synthase 2 (OAS2) was identified as the key differentially expressed gene by RNA sequencing and bioinformatics analysis. Furthermore, high expression of OAS2 was found in aorta of AT1-AA-positive rats; knockdown of OAS2 by siRNA can reverse the phenotypic transition of VSMCs induced by AT1-AA. In summary, this study suggests that AT1-AA can promote phenotypic transition of VSMCs through AT1R-OAS2 pathway, and OAS2 might serve as a potential therapeutic target to prevent pathological phenotypic transition of smooth muscle cells.

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis.

Thermomorphogenesis and the heat shock (HS) response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and HEAT SHOCK FACTOR A1s (HSFA1s), respectively. Little is known about whether these responses are interconnected and whether they are activated by similar mechanisms. An analysis of transcriptome dynamics in response to warm temperature (28°C) treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis thaliana. Meanwhile, a loss-of-function HSFA1 quadruple mutant (hsfa1-cq) was insensitive to warm temperature-induced hypocotyl growth. In hsfa1-cq plants grown at 28°C, the protein and transcript levels of PIF4 were greatly reduced, and the circadian rhythm of many thermomorphogenesis-related genes (including PIF4) was disturbed. Additionally, the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure, whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the mutant. Taken together, these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature, and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.