Interstitial Fluid Shear Stress Induces the Synthetic Phenotype Switching of VSMCs to Release Pro-calcified Extracellular Vesicles via EGFR-MAPK-KLF5 Pathway.

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.

Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy.

BACKGROUND: The accumulation of senescent microglia has been highlighted as a critical contributor to the progression of tauopathies. Irisin, a muscle-derived hormone produced by the proteolytic cleavage of Fibronectin-domain III containing 5 (FNDC5), mediates the pleiotropic effects of exercise on the physical body. Herein, we investigate the potential role of irisin in microglial senescence in tauopathies. METHODS: To model tauopathies both in vivo and in vitro, we utilized P301S tau transgenic mice and tau K18 fibril-treated microglia BV2 cells, respectively. We first examined the expression of the irisin expression and senescence phenotypes of microglia in tauopathies. Subsequently, we investigated the impact of irisin on microglial senescence and its underlying molecular mechanisms. RESULT: We observed a reduction in irisin levels and an onset of premature microglial senescence both in vivo and in vitro. Irisin administration was found to counteract microglial senescence and ameliorate cognitive decline in P301S mice. Mechanistically, irisin effectively inhibited microglial senescence by stimulating the expression of mitochondrial transcription factor A (TFAM), a master regulator of mitochondrial respiratory chain biogenesis, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS). Silencing TFAM eliminated the inhibitory effect of irisin on microglial senescence as well as the restorative effect of irisin on mitochondrial OXPHOS. Furthermore, the SIRT1/PGC1α signaling pathway appeared to be implicated in irisin-mediated upregulation of TFAM. CONCLUSION: Taken together, our study revealed that irisin mitigated microglial senescence via TFAM-driven mitochondrial biogenesis, suggesting a promising new avenue for therapeutic strategies targeting tauopathies.

STAT3 phosphorylation at Tyr705 affects DRP1 (dynamin-related protein 1) controlled-mitochondrial fission during the development of apoptotic-resistance in pulmonary arterial endothelial cells.

BACKGROUND: The apoptosis-resistant pulmonary arterial endothelial cells (PAECs) are known to be major players in the pulmonary remodeling of pulmonary arterial hypertension (PAH) and exhibit an abnormal metabolic profile with mitochondrial dysfunction. Mitochondrial fission has been shown to regulate the apoptosis of several cell types, but this is largely unexplored in the PAECs. OBJECTIVE: The roles of mitochondrial fission control by Dynamin related protein-1 (DRP1) in the development of PAECs apoptosis suppression were investigated in present study and the potential mechanisms behind this were furtherly explored. METHODS: The mitochondrial morphology was investigated in PAECs from PAH rats with the pulmonary plexiform lesions, and the relations of it with DRP1 expression and apoptosis were furtherly identified in apoptosis-resistant PAECs induced by hypoxia. PAECs were isolated from rats with severe PAH and from normal subjects, the apoptotic-resistant PAECs were induced by hypoxia. DRP1 gene knockdown was achieved via DRP1-siRNA, DRP1 and STAT3 phosphorylation were blocked using its inhibitors, respectively. Apoptosis was analyzed by flow cytometry, and mitochondrial morphology was investigated by transmission electron microscope and confocal microscopy. RESULTS: The PAECs isolated from PAH rats with the pulmonary plexiform-like lesions and displayed lower apoptotic rate with increased DRP1 expression and mitochondrial fragmentation. In addition, similar observations were achieved in apoptosis-resistant PAECs induced by hypoxia. Targeting DRP1 using siRNA and pharmacologic blockade prevented the mitochondrial fission and subsequent apoptotic resistance in PAECs under hypoxia. Mechanistically, STAT3 phosphorylation at Tyr705 was shown to be activated in both PAH and hypoxia-treated PAECs, leading to the regulation of DRP1 expression. Of importance, targeting STAT3Tyr705 phosphorylation prevented DRP1 disruption on apoptosis in PAECs under hypoxia. CONCLUSIONS: These data indicated that STAT3 phosphorylation at Tyr705 impacted DRP1-controlled mitochondrial fission during the development of apoptosis-resistance in PAECs, suggesting mitochondrial dynamics may represent a therapeutic target for PAH.

Ultrasonic-assisted green extraction and incorporation of Spirulina platensis bioactive components into turmeric essential oil-in-water nanoemulsion for enhanced antioxidant and antimicrobial activities.

The utilization of essential oils as natural antioxidants and preservatives is limited by high volatility, poor water solubility, and long-term instability. To address this, a novel ultrasonic-assisted method was used to prepare and stabilize a nanoemulsion of turmeric essential oil-in-water, incorporating bioactive components extracted from Spirulina platensis. Ultrasonic treatment enhanced the extraction efficacy and nanoemulsion stability. Algal biomass subjected to ultrasonic treatment (30 min at 80% amplitude) yielded a dry extract of 73.66 ± 3.05%, with the highest protein, phenolic, phycocyanin, and allophycocyanin content, as well as maximum emulsifying activity. The resulting nanoemulsion (5% oil, 0.3% extract, 10 min ultrasonic treatment) showed reduced particle size (173.31 ± 2.24 nm), zeta potential (-36.33 ± 1.10 mV), low polydispersity index, and enhanced antioxidant and antibacterial properties. Rheology analysis indicated shear-thinning behavior, while microscopy and spectroscopy confirmed structural changes induced by ultrasonic treatment and extract concentration. This initiative developed a novel ultrasonic-assisted algal-based nanoemulsion with antioxidant and antibacterial properties.

Innovative orthogonal two-dimensional reversed-phase liquid chromatography × supercritical fluid chromatography with a phenyl/tetrazole stationary phase for the preparative isolation of diarylheptanoids.

In this investigation, we successfully isolated and purified natural diarylheptanoids using an orthogonal offline two-dimensional RPLC × SFC approach, employing only the phenyl/tetrazole stationary phase. First, a styrene-divinylbenzene matrix medium pretreatment liquid chromatography system effectively processed chlorophyll-containing plant extract solution with a recovery rate of 33.8 %, obviating the need for concentration steps. Subsequently, an offline two-dimensional RPLC × SFC employing only the phenyl/tetrazole stationary phase achieved a remarkable 96.38 % orthogonality and was established and utilized in the preparative separation and purification of natural products. Finally, the constructed single stationary phase highly orthogonal RPLC × SFC system was successfully applied in the preparative separation and purification of natural diarylheptanoids from the Saxifraga tangutica target fraction and yielded four diarylheptanoids with purities exceeding 95 %.

Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

Surface-Enriched Room-Temperature Liquid Bismuth for Catalytic CO2 Reduction.

Bismuth-based electrocatalysts are effective for carbon dioxide (CO2) reduction to formate. However, at room temperature, these materials are only available in solid state, which inevitably suffers from surface deactivation, declining current densities, and Faradaic efficiencies. Here, the formation of a liquid bismuth catalyst on the liquid gallium surface at ambient conditions is shown as its exceptional performance in the electrochemical reduction of CO2 (i.e., CO2RR). By doping a trace amount of bismuth (740 ppm atomic) in gallium liquid metal, a surface enrichment of bismuth by over 400 times (30 at%) in liquid state is obtained without atomic aggregation, achieving 98% Faradic efficiency for CO2 conversion to formate over 80 h. Ab initio molecular simulations and density functional theory calculations reveal that bismuth atoms in the liquid state are the most energetically favorable sites for the CO2RR intermediates, superior to solid Bi-sites, as well as joint GaBi-sites. This study opens an avenue for fabricating high-performing liquid-state metallic catalysts that cannot be reached by elementary metals under electrocatalytic conditions.

Optimizing focus: switchable modes and sub-diffraction spots in inverse circular Airy beams.

We report an experimental investigation into the tight-focusing characteristics of linearly polarized inverse circular Airy beams (ICABs). Our study reveals that tightly focused ICABs exhibit Bessel-like, needle-like, or dual foci profiles depending on whether the main ring's radius is smaller than, equal to, or larger than the critical radius. The emergence of the dual foci structure is attributed to the constrained entrance aperture of the microscope objective (MO). In contrast to traditional Gaussian beams (GBs), ICABs demonstrate remarkable advantages in terms of focal spot size. Notably, we observe a focal spot with a size of 245 nm, representing a 26.4% reduction compared to the diffraction limit. These unique properties open up promising avenues for potential applications in optical multi-plane particle trapping, conveying, and super-resolution optical imaging.

Histological and Single-nucleus Transcriptome Analyses Unveil the Specialized Functions of Ligular Sclerenchyma Cells and Key Regulators of Leaf Angle in Maize.

Leaf angle (LA) is a crucial factor affecting planting density and yield in maize. However, the regulatory mechanisms underlying LA formation remain largely unknown. In this study, we conducted a comparative histological analysis of the ligular region across various maize inbred lines, revealing that LA size is significantly influenced by a two-step regulatory process involving initial cell elongation followed by subsequent lignification in the ligular adaxial sclerenchyma cells (SC). We performed both bulk and single-nucleus RNA sequencing, generated a comprehensive transcriptomic atlas of the ligular region, and identified numerous genes enriched in the hypodermal cells that may influence their specialization into SC. Furthermore, we functionally characterized two genes encoding atypical basic helix-loop-helix (bHLH) transcription factors, bHLH30 and its homolog bHLH155, respectively, which are highly expressed in the elongated adaxial cells. Genetic analyses revealed that bHLH30 and bHLH155 positively regulate LA expansion, and molecular experiments demonstrated their ability to activate the transcription of genes involved in cell elongation and lignification of SC. These findings highlight the specialized functions of ligular adaxial SC in LA regulation by restricting the further extension of ligular cells and enhancing mechanical strength. The transcriptomic atlas of ligular region at single -nucleus resolution not only deepens our understanding of LA regulation but also identifies numerous potential targets for optimizing plant architecture in modern maize breeding.

Major changes in prevalence and genotypes of rotavirus diarrhea in Beijing, China after RV5 rotavirus vaccine introduction.

To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test-negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011-2018, RVA-positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9-VIP[8]-III between 2019 and 2021 to G8-VP[8]-III in 2022, and P[8] sequences from G8-VP[8]-III strains formed a new branch called P[8]-IIIb. The complete genotype of G8-VP[8]-III was G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%-98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P[8], which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.

Controllable Fabrication of Highly Ordered Spherical Microcavity Arrays by Replica Molding of In Situ Self-Emulsified Droplets.

Ordered spherical hollow micro- and nanostructures hold great appeal in the fields of cell biology and optics. However, it is extremely challenging for standard lithography techniques to achieve spherical micro-/nanocavities. In this paper, we describe a simple, cost-effective, and scalable approach to fabricate highly ordered spherical microcavity arrays by replica molding of in situ self-emulsified droplets. The in situ self-emulsion involves a two-step process: discontinuous dewetting-induced liquid partition and interfacial tension-driven liquid spherical transformation. Subsequent replica molding of the droplets creates spherical microcavity arrays. The shapes and sizes of the microcavities can be easily modulated by varying the compositions of the droplet templates or utilizing an osmotically driven water permeation. To demonstrate the utility of this method, we employed it to create a spherical microwell array for the mass production of embryoid bodies with high viability and minimal loss. In addition, we also demonstrated the optical functions of the generated spherical microcavities by using them as microlenses. We believe that our proposed method will open exciting avenues in fields ranging from regenerative medicine and microchemistry to optical applications.

Pulsed electric field treatment improves the oil yield, quality, and antioxidant activity of virgin olive oil.

Pulsed electric field (PEF) is an innovative technique used to assist in the extraction of vegetable oils. There has been no research on the effects of PEF on virgin olive oil (VOO) quality and antioxidant activity to date. The present study aimed to analyze the effects of PEF on oil yield, quality, and in vitro antioxidant activity of "Koroneiki" extra virgin olive oil. The results show that the PEF treatment increased the oil yield by 5.6%, but had no significant effect on the saponification value, K232, K270, and ∆K value of the VOO. PEF treatment reduced the oleic acid content by 3.12%, but had no significant effect on the content of palmitic acid, linoleic acid, linolenic acid, arachidonic acid, stearic acid, oleic acid, and palmitic acid. After PEF treatment, the levels of total phenolics, total flavonoids, and oleuropein increased by 7.6%, 18.3% and 76%, respectively. There was no significant effect on the levels of 4 phenolic acids (vanillic acid, p-coumaric acid, ferulic acid and cinnamic acid), 2 lignans (lignans and apigenin), hydroxytyrosol, and 3 pigments (lutein, demagnetized chlorophyll, and carotenoids). In addition, PEF treatment significantly increased the content of tocopherols, with α, ß, γ, and δ tocopherols increasing by 9.8%, 10.7%, 13.6% and 38.4%, respectively. The free radical scavenging ability of DPPH and ABTS was also improved. In conclusion, the use of PEF significantly increased the yield of VOO oil as well as the levels of total phenolics, total flavonoids, oleuropein, tocopherol, and in vitro antioxidant activity.

Ketogenesis attenuated KLF5 disrupts iron homeostasis via LIF to confer oxaliplatin vulnerability in colorectal cancer.

Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

Nanobubble technology to enhance energy recovery from anaerobic digestion of organic solid wastes: Potential mechanisms and recent advancements.

Nanobubble (NB) technology has gained popularity in the environmental field owing to its distinctive characteristics and ecological safety. More recently, the application of NB technology in anaerobic digestion (AD) systems has been proven to promote substrate degradation and boost the production of biogas (H2 and/or CH4). This review presents the recent advancements in the application of NB technology in AD systems. Meanwhile, it also sheds light on the underlying mechanisms of NB technology that contribute to the enhanced biogas production from AD of organic solid wastes. Specifically, the working principles of the NB generator are first summarized, and then the structure of the NB generator is optimized to accommodate the demand for NB characteristics in the AD system. Subsequently, it delves into a detailed discussion of how the addition of nanobubble water (NBW) affects AD performance and the different factors that NB can potentially contribute. As a simple and environmentally friendly additive, NBW was commonly used in the AD process to enhance the fluidity and mass transfer characteristics of digestate. Additionally, NB has the potential to enhance the functionality of different types of microbial enzymes that play crucial roles in the AD process. This includes boosting extracellular hydrolase activities, optimizing coenzyme F420, and improving cellulase function. Finally, it is proposed that NBW has development potential for the pretreatment of substrate and inoculum, with future development being directed towards this aim.

Elevated type I IFN signalling directly affects CD8+ T-cell distribution and autoantigen recognition of the skeletal muscles in active JDM patients.

The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.

Early autism diagnosis based on path signature and Siamese unsupervised feature compressor.

Autism spectrum disorder has been emerging as a growing public health threat. Early diagnosis of autism spectrum disorder is crucial for timely, effective intervention and treatment. However, conventional diagnosis methods based on communications and behavioral patterns are unreliable for children younger than 2 years of age. Given evidences of neurodevelopmental abnormalities in autism spectrum disorder infants, we resort to a novel deep learning-based method to extract key features from the inherently scarce, class-imbalanced, and heterogeneous structural MR images for early autism diagnosis. Specifically, we propose a Siamese verification framework to extend the scarce data, and an unsupervised compressor to alleviate data imbalance by extracting key features. We also proposed weight constraints to cope with sample heterogeneity by giving different samples different voting weights during validation, and used Path Signature to unravel meaningful developmental features from the two-time point data longitudinally. We further extracted machine learning focused brain regions for autism diagnosis. Extensive experiments have shown that our method performed well under practical scenarios, transcending existing machine learning methods and providing anatomical insights for autism early diagnosis.

PEG-crosslinked O-carboxymethyl chitosan films with degradability and antibacterial activity for food packaging.

This study developed a kind of PEG-crosslinked O-carboxymethyl chitosan (O-CMC-PEG) with various PEG content for food packaging. The crosslinking agent of isocyanate-terminated PEG was firstly synthesized by a simple condensation reaction between PEG and excess diisocyanate, then the crosslink between O-carboxymethyl chitosan (O-CMC) and crosslinking agent occurred under mild conditions to produce O-CMC-PEG with a crosslinked structure linked by urea bonds. FT-IR and 1H NMR techniques were utilized to confirm the chemical structures of the crosslinking agent and O-CMC-PEGs. Extensive research was conducted to investigate the impact of the PEG content (or crosslinking degree) on the physicochemical characteristics of the casted O-CMC-PEG films. The results illuminated that crosslinking and components compatibility could improve their tensile features and water vapor barrier performance, while high PEG content played the inverse effects due to the microphase separation between PEG and O-CMC segments. The in vitro degradation rate and water sensitivity primarily depended on the crosslinking degree in comparison with the PEG content. Furthermore, caused by the remaining -NH2 groups of O-CMC, the films demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. When the PEG content was 6% (medium crosslinking degree), the prepared O-CMC-PEG-6% film possessed optimal tensile features, high water resistance, appropriate degradation rate, low water vapor transmission rate and fine broad-spectrum antibacterial capacity, manifesting a great potential for application in food packaging to extend the shelf life.

Decoding the molecular concerto: Toxicotranscriptomic evaluation of microplastic and nanoplastic impacts on aquatic organisms.

The pervasive and steadily increasing presence of microplastics/nanoplastics (MPs/NPs) in aquatic environments has raised significant concerns regarding their potential adverse effects on aquatic organisms and their integration into trophic dynamics. This emerging issue has garnered the attention of (eco)toxicologists, promoting the utilization of toxicotranscriptomics to unravel the responses of aquatic organisms not only to MPs/NPs but also to a wide spectrum of environmental pollutants. This review aims to systematically explore the broad repertoire of predicted molecular responses by aquatic organisms, providing valuable intuitions into complex interactions between plastic pollutants and aquatic biota. By synthesizing the latest literature, present analysis sheds light on transcriptomic signatures like gene expression, interconnected pathways and overall molecular mechanisms influenced by various plasticizers. Harmful effects of these contaminants on key genes/protein transcripts associated with crucial pathways lead to abnormal immune response, metabolic response, neural response, apoptosis and DNA damage, growth, development, reproductive abnormalities, detoxification, and oxidative stress in aquatic organisms. However, unique challenge lies in enhancing the fingerprint of MPs/NPs, presenting complicated enigma that requires decoding their specific impact at molecular levels. The exploration endeavors, not only to consolidate existing knowledge, but also to identify critical gaps in understanding, push forward the frontiers of knowledge about transcriptomic signatures of plastic contaminants. Moreover, this appraisal emphasizes the imperative to monitor and mitigate the contamination of commercially important aquatic species by MPs/NPs, highlighting the pivotal role that regulatory frameworks must play in protecting all aquatic ecosystems. This commitment aligns with the broader goal of ensuring the sustainability of aquatic resources and the resilience of ecosystems facing the growing threat of plastic pollutants.

Targeted metabolomics-based understanding of the sleep disturbances in drug-naïve patients with schizophrenia.

BACKGROUND: Sleep disturbances are a common occurrence in patients with schizophrenia, yet the underlying pathogenesis remain poorly understood. Here, we performed a targeted metabolomics-based approach to explore the potential biological mechanisms contributing to sleep disturbances in schizophrenia. METHODS: Plasma samples from 59 drug-naïve patients with schizophrenia and 36 healthy controls were subjected to liquid chromatography-mass spectrometry (LC-MS) targeted metabolomics analysis, allowing for the quantification and profiling of 271 metabolites. Sleep quality and clinical symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS), respectively. Partial correlation analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) model were used to identify metabolites specifically associated with sleep disturbances in drug-naïve schizophrenia. RESULTS: 16 characteristic metabolites were observed significantly associated with sleep disturbances in drug-naïve patients with schizophrenia. Furthermore, the glycerophospholipid metabolism (Impact: 0.138, p<0.001), the butanoate metabolism (Impact: 0.032, p=0.008), and the sphingolipid metabolism (Impact: 0.270, p=0.104) were identified as metabolic pathways associated with sleep disturbances in drug-naïve patients with schizophrenia. CONCLUSIONS: Our study identified 16 characteristic metabolites (mainly lipids) and 3 metabolic pathways related to sleep disturbances in drug-naïve schizophrenia. The detection of these distinct metabolites provide valuable insights into the underlying biological mechanisms associated with sleep disturbances in schizophrenia.

Optimization Design of Mix Proportion for Fly Ash-Silica Fume-Basalt Fiber-Polypropylene Fiber Concrete under Steam Curing Condition.

To enhance the physical and mechanical characteristics of steam-cured concrete, an orthogonal experimental design was utilized to examine the effects of varying contents of fly ash (0 wt%, 10 wt%, 15 wt%, 20 wt%), silica fume (0 wt%, 5 wt%, 10 wt%, 15 wt%), basalt fiber (0 vol%, 0.05 vol%, 0.1 vol%, 0.2 vol%), and polypropylene fiber (0 vol%, 0.05 vol%, 0.1 vol%, 0.2 vol%) on its mechanical properties. Utilizing range and variance analyses, this study identified four preliminary optimized compositions of concrete incorporating fly ash, silica fume, basalt fiber, and polypropylene fiber. On this basis, in order to determine the optimal mix proportion, the mechanical performances, the pore characteristics, and the microstructure of four optimized mix proportions were analyzed. According to the results of macroscopic, fine, and microscopic multi-scale tests, the addition of 15 wt% fly ash, 10 wt% silica ash, 0.2 vol% basalt fiber, and 0.1 vol% polypropylene fiber to the steamed concrete is the best to improve the performance of the steamed concrete. Compared to ordinary concrete, the compressive strength increases by 28%, the tensile strength increases by 40%, and the porosity decreases by 47.2%.