Preparation and modification of polymer microspheres, application in wastewater treatment: A review.

The removal of various pollutants from water is necessary due to the increasing requirements for the removal of various pollutants from wastewater and the quality of drinking water. Polymer microspheres are regarded as exemplary adsorbent materials due to their high adsorption efficiency, excellent adsorption performance, and ease of handling. Herein, the advantages and disadvantages of different preparation methods, modifications, applications and the current research status of polymer microspheres are summarized at large. Furthermore, the enhanced performance of modified composite microspheres is emphasized, including adsorption efficiency, thermal stability, and significant improvements in physical and chemical properties. Subsequently, the current applications and potential of polymeric microspheres for wastewater treatment, including the removal of inorganic and organic pollutants, heavy metal ions, and other contaminants are summarized. Finally, future research directions for polymer microspheres are proposed, outlining the challenges and solutions associated with the application of polymer microspheres in wastewater treatment.

Microsecretory adenocarcinoma of the hard palate: a case report and literature review.

Microsecretory adenocarcinoma (MSA) is a new type of salivary gland neoplasm identified in the 2022 World Health Organization Classification of Head and Neck Tumour (Skalova et al., Head Neck Pathol 16:40-53, 2022) and is characterized by a unique set of histomorphologic and immunohistochemical features and a recurrent MEF2C::SS18 fusion. MSA was initially misdiagnosed as another salivary gland tumour due to its similar morphology; until recently, only fewer than 50 cases were reported. We present a case of MSA of the hard palate with diverse architectural growth patterns, bland cytological features, abundant basophilic intraluminal secretions and fibromyxoid stroma. The tumour cells were positive for the SOX10, S100, and p63 protein and negative for the p40 protein according to immunohistochemistry. SS18 gene rearrangement was demonstrated via break-apart fluorescence in situ hybridization. We also provided a comprehensive literature review and integrated the clinicopathological features, immunophenotype, and molecular alterations of the disease. A comprehensive understanding of MSA enables us to accurately distinguish and categorize MSA from other salivary gland tumours with analogous morphologies.

A precise microdissection strategy enabled spatial heterogeneity analysis on the targeted region of formalin-fixed paraffin-embedded tissues.

In recent years, the development of spatial transcriptomic technologies has enabled us to gain an in-depth understanding of the spatial heterogeneity of gene expression in biological tissues. However, a simple and efficient tool is required to analyze multiple spatial targets, such as mRNAs, miRNAs, or genetic mutations, at high resolution in formalin-fixed paraffin-embedded (FFPE) tissue sections. In this study, we developed hydrogel pathological sectioning coupled with the previously reported Sampling Junior instrument (HPSJ) to assess the spatial heterogeneity of multiple targets in FFPE sections at a scale of 180 µm. The HPSJ platform was used to demonstrate the spatial heterogeneity of 9 ferroptosis-related genes (TFRC, NCOA4, FTH1, ACSL4, LPCAT3, ALOX12, SLC7A11, GLS2, and GPX4) and 2 miRNAs (miR-185-5p and miR522) in FFPE tissue samples from patients with triple-negative breast cancer (TNBC). The results validated the significant heterogeneity of ferroptosis-related mRNAs and miRNAs. In addition, HPSJ confirmed the spatial heterogeneity of the L858R mutation in 7 operation-sourced and 4 needle-biopsy-sourced FFPE samples from patients with lung adenocarcinoma (LUAD). The successful detection of clinical FFPE samples indicates that HPSJ is a precise, high-throughput, cost-effective, and universal platform for analyzing spatial heterogeneity, which is beneficial for elucidating the mechanisms underlying drug resistance and guiding the prescription of mutant-targeted drugs in patients with tumors.

Patient-reported physical well-being predicts good long-term survival of hematopoietic stem cell transplantation.

AIM: This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. METHODS: We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. RESULTS: Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. CONCLUSIONS: Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.

Distribution and transformation of potentially toxic elements in cracks under coal mining disturbance in farmland.

The ground cracks resulting from coal mining activities induce alterations in the physical and chemical characteristics of soil. However, limited knowledge exists regarding the impact of subsidence caused by coal mining on the distribution of potentially toxic elements (PTEs) fractions in farmland soil. In this study, we collected 19 soil profiles at varying depths from the soil surface and at horizontal distances of 0, 1, 2, and 5 m from the vertical crack. Using BCR extraction fractionation, we determined the geochemical fractions and total concentrations of Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) to investigate their ecological risk, spatial fraction distribution, and main influencing factors. Results showed that the E r i values of Cd appearing in 68.7% of the samples were higher than 40 and less than 80, presented a moderate ecological risk. Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were mainly bound to residual fractions (> 60%) with lower mobility and Cd was dominated by F1 (acid-soluble fractions, 50%) and F2 (reducible fractions, 29%) in surface soil (0-20 cm). The geochemical fractionation revealed that the mobile fractions (F1-acid-soluble and F2-reducible) of PTEs were primarily located near the crack, influenced by available potassium. In contrast, the less mobile fractions (F3-oxidizable and F4-residual) exhibited higher concentrations at distances of 2 and 5 m from the crack, except for arsenic, influenced by the presence of clay particles and available phosphorus.

Novel in-situ encapsulation of tin phosphide particles in MXene conductive networks as anode materials of the durable sodium-ion battery.

Sodium-ion battery (SIB) is one of potential alternatives to lithium-ion battery, because of abundant resources and lower price of sodium. High electrical conductivity and long-term durability of MXene are advantageous as the anode material of SIB, but low energy density restricts applications. Tin phosphide possesses high theoretical capacity, low redox potential, and large energy density, but volume expansion reduces its cycling stability. In this study, tin phosphide particles are in-situ encapsulated into MXene conductive networks (SnxPy/MXene) by hydrothermal and phosphorization processes as novel anode materials of SIB. MXene amounts and hydrothermal durations are investigated to evenly distribute SnxPy in MXene. After 100 cycles, SnxPy/MXene reaches high specific capacities of 438.8 and 314.1 mAh/g at 0.2 and 1.0 A/g, respectively. The capacity retentions of 6.0% and 73.6% at 0.2 A/g are respectively obtained by SnxPy and SnxPy/MXene. The better specific capacity and cycling stability of SnxPy/MXene are attributed to less volume expansion of SnxPy during charge/discharge processes and relieved self-stacking of MXene by encapsulating SnxPy particles between MXene layers. Electrochemical impedance spectroscopy and Galvanostatic intermittent titration technique are also applied to analyze the charge storage mechanism in SIB. Higher sodium ion diffusion coefficient and smaller charge-transfer resistance are obtained by SnxPy/MXene.

Antibiotics suppress the expression of antimicrobial peptides and increase sensitivity of Cydia pomonella to granulosis virus.

Cydia pomonella granulovirus (CpGV) is a highly specific and environmentally friendly pathogenic virus successfully used as a biological insecticide against codling moth larvae. Continuous application of CpGV has led to high levels of resistance in codling moth, Cydia pomonella (C. pomonella). Nevertheless, the specific molecular mechanisms underlying the development of resistance in codling moths to CpGV have been rarely investigated. This study explored the potential antiviral immune roles of codling moth antimicrobial peptides (AMPs) against CpGV. A total of 11 AMP genes classified in cecropin, defensin, gloverin, and attacin subfamilies, were identified in the codling moth genome. The cecropin and gloverin subfamilies were found to be the ancestral genes of the AMP gene family. The expression of two AMP genes (CmGlo1 and CmAtt1) significantly increased following CpGV challenge, and CmGlo1 and CmAtt1 gene silencing resulted in a significant increase in CpGV replication in codling moth larvae. The hemolymph and fat body serve as major viral immune functional tissues in codling moth larvae. Moreover, zhongshengmycin significantly reduced the diversity and abundance of codling moth larvae gut microbiota, thereby suppressing the expression of CmAtt1 AMP gene. We also found that the combination of the virus with zhongshengmycin would enhance the insecticidal effects of CpGV. This study provides the first explanation of the molecular mechanisms driving CpGV immune function development in codling moths, approached from the perspective of the codling moth itself. Additionally, we introduced an alternative approach to combat codling moth in the field by combining antibiotics with biopesticides to amplify the insecticidal effects of the latter.

Facile synthesis of tantalum decorated on iron selenide with nitrogen-doped graphene hybrid for the sensitive detection of trolox in berries: Density functional theory interpretation.

This work presents a hydrothermal method followed by a sonochemical treatment for synthesizing tantalum decorated on iron selenide (Ta/FeSe2) integrated with nitrogen-doped graphene (NGR) as a susceptible electrode material for detecting trolox (TRX) in berries samples. The surface morphology, structural characterizations, and electrochemical performances of the synthesized Ta/FeSe2/NGR composite were analyzed via spectrophotometric and voltammetry techniques. The GCE modified with Ta/FeSe2/NGR demonstrated an impressive linear range of 0.1 to 580.3 µM for TRX detection. Additionally, it achieved a remarkable limit of detection (LOD) of 0.059 µM, and it shows a high sensitivity of 2.266 µA µÐœ-1 cm-2. Here, we used density functional theory (DFT) to investigate the structures of TRX and TRX quinone and the locations of energy levels and electron transfer sites. The developed sensor exhibits significant selectivity, satisfactory cyclic and storage stability, and notable reproducibility. Moreover, the practicality of TRX was assessed in different types of berries, yielding satisfactory recoveries.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Dual Z-scheme heterojunction Ce2Sn2O7/Ag3PO4/V@g-C3N4 for increased photocatalytic degradation of the food additive tartrazine, in the presence of persulfate: Kinetics, toxicity, and density functional theory studies.

This study involved the synthesis of a Ce2Sn2O7/Ag3PO4/V@g-C3N4 composite through hydrothermal methods, followed by mechanical grinding. The resulting heterojunction exhibited improved catalytic activity under visible light by effectively separating electrons and holes (e-/h+). The degradation of Tartrazine (TTZ) reached 93.20% within 50 min by employing a ternary composite at a concentration of 10 mg L-1, along with 6 mg L-1 of PS. The highest pseudo-first-order kinetic constant (0.1273 min-1 and R2 = 0.951) was observed in this system. The dual Z-scheme heterojunction is developed by Ce2Sn2O7, Ag3PO4, and V@g-C3N4, and it may increase the visible light absorption range while also accelerating charge carrier transfer and separation between catalysts. The analysis of the vulnerability positions and degradation pathways of TTZ involved the utilization of density functional theory (DFT) and gas chromatography-mass spectrometry (GC-MS) to examine the intermediate products. Therefore, Ce2Sn2O7/Ag3PO4/V@g-C3N4 is an excellent ternary nanocomposite for the remediation of pollutants.

Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery.

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the ß-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

Caspase-8 promotes NLRP3 inflammasome activation mediates eye development defects in zebrafish larvae exposed to perfulorooctane sulfonate (PFOS).

Epidemiological evidence showed that serum high perfluorooctane sulfonate (PFOS) levels are associated with multiple eye related diseases, but the potential underlying molecular mechanisms remain poorly understood. Zebrafish and photoreceptor cell (661w) models were used to investigate the molecular mechanism of PFOS induced eye development defects. Our results showed a novel molecular mechanism of PFOS-induced inflammation response-mediated photoreceptor cell death associated with eye development defects. Inhibition of Caspase-8 activation significantly decreased photoreceptor cell death in PFOS exposure. Mechanistically, Toll-like receptor 4 (TLR4) mediates activation of Caspase-8 promote activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome to elicit maturation of interleukin-1 beta (IL-1ß) via Caspase-1 activation, facilitating photoreceptor cell inflammation damage in PFOS exposure. In addition, we also made a novel finding that Caspase-3 activation was increased via Caspase-8 activation and directly intensified cell death. Our results show the important role of Caspase-8 activation in PFOS induced eye development defects and highlight Caspase-8 mediated activation of the NLRP3 inflammation triggers activation of Caspase-1 and promote the maturation of IL-1ß in retinal inflammatory injury.

Transcriptional Regulation and Gene Mapping of Internode Elongation and Late Budding in the Chinese Cabbage Mutant lcc.

Two important traits of Chinese cabbage, internode length and budding time, destroy the maintenance of rosette leaves in the vegetative growth stage and affect flowering in the reproductive growth stage. Internodes have received much attention and research in rice due to their effect on lodging resistance, but they are rarely studied in Chinese cabbage. In Chinese cabbage, internode elongation affects not only the maintenance of rosette leaves but also bolting and yield. Budding is also an important characteristic of Chinese cabbage entering reproductive growth. Although many studies have reported on flowering and bolting, studies on bud emergence and the timing of budding are scarce. In this study, the mutant lcc induced by EMS (Ethyl Methane Sulfonate) was used to study internode elongation in the seedling stage and late budding in the budding stage. By comparing the gene expression patterns of mutant lcc and wild-type A03, 2280 differentially expressed genes were identified in the seedling stage, 714 differentially expressed genes were identified in the early budding stage, and 1052 differentially expressed genes were identified in the budding stage. Here, the transcript expression patterns of genes in the plant hormone signaling and clock rhythm pathways were investigated in relation to the regulation of internode elongation and budding in Chinese cabbage. In addition, an F2 population was constructed with the mutants lcc and R500. A high-density genetic map with 1602 marker loci was created, and QTLs for internode length and budding time were identified. Specifically, five QTLs for internode length and five QTLs for budding time were obtained. According to transcriptome data analysis, the internode length candidate gene BraA02g005840.3C (PIN8) and budding time candidate genes BraA02g003870.3C (HY5-1) and BraA02g005190.3C (CHS-1) were identified. These findings provide insight into the regulation of internode length and budding time in Chinese cabbage.

Adaptive UAV Navigation Method Based on AHRS.

To address the inaccuracy of the Constant Acceleration/Constant Velocity (CA/CV) model as the state equation in describing the relative motion state in UAV relative navigation, an adaptive UAV relative navigation method is proposed, which is based on the UAV attitude information provided by Attitude and Heading Reference System (AHRS). The proposed method utilizes the AHRS output attitude parameters as the benchmark for dead reckoning and derives a relative navigation state equation with attitude error as process noise. By integrating the extended Kalman filter output for relative state estimation and employing an adaptive decision rule designed using the innovation of the filter update phase, the proposed method recalculates motion states deviating from the actual motion using the Tasmanian Devil Optimization (TDO) algorithm. The simulation results show that, compared with the CA/CV model, the proposed method reduces the relative position errors by 12%, 23%, and 32% in the X, Y, and Z directions, respectively, and that it reduces the relative velocity errors by 350%, 330%, and 300%, respectively. There is a significant improvement in the relative navigation accuracy.

Systematic optimization and evaluation of culture conditions for the construction of circulating tumor cell clusters using breast cancer cell lines.

BACKGROUND: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. METHODS: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. RESULTS: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. CONCLUSIONS: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

[Land Change Simulation and Grassland Carbon Storage in the Loess Plateau Based on SSP-RCP Scenarios].

Exploring the spatial distribution of land use/coverage (LUCC) and ecosystem carbon reserves in the future of climate change can provide a scientific basis for optimizing the distribution of land resources and formulating social economic sustainable development policies. In this study, we integrated the plaques generating land use simulation (PLUS) model and ecosystem services and weighing comprehensive evaluation (InVEST) model. Based on the CMIP6-based sharing socio-economic path and representative concentration path (SSP-RCP), we evaluated the Loess Plateau for time and space dynamic changes in LUCC and ecosystem carbon reserves, analyzed the impact of driving factors on different regions, and explored the correlation between carbon reserves in various regions. The results showed:① In the future, the three scenarios were similar to the LUCC changes. The area of cultivated land, grassland, and unused land would be reduced to varying degrees, and the construction land had expanded sharply. The increase in the three scenarios was 29.23%-53.56% (SSP126), 34.59%-63.28% (SSP245), and 42.80%-73.27% (SSP585). ② Compared with that in 2020, the carbon reserves of SSP126 sites in 2040 increased by 1.813 8×106 t, and in the remaining scenarios it would continue to decline. By 2060, the grassland carbon reserves in the three scenarios decreased by 13.391×106, 33.548×106, and 85.871×106 t, respectively. ③ From the perspective of space correlation, the carbon reserves of the Loess Plateau were correlated between cities. The difference in future scenarios was not significant. The hotspots were distributed in the middle and north of the research area. There was no obvious cold spot area. ④ The changes in land use were predicted to increase or lose carbon reserves. Forestry, cultivated land, and grassland had more carbon reserves those in than other land types. Increasing their area and restrictions on the conversion of other land types should increase the ecosystem carbon reserves.

Behavioral toxicity and neurotoxic mechanisms of PLA-PBAT biodegradable microplastics in zebrafish.

Escalation of ecological concern due to biodegradable plastics has attracted the attention of many contemporary researchers. This study searched to investigate the acute and sub-chronic toxicity of polylactic acid (PLA) and polybutyleneadipate-co-terephthalate (PLA-PBAT) bio-microplastics on 3-month-old zebrafish to elucidate their potential toxic mechanisms. Acute toxicity assessments revealed 96 h-LC50 value of 12.69 mg/L for PLA-PBAT. Sub-chronic exposure of over 21 days revealed deviations in critical behavioral patterns and physiological indicators. In treated groups, weight gain and specific growth rates were significantly lower than those obtained for the control group, such that high doses induced significant reductions in total organ coefficient (p < 0.05). A positive correlation was observed between zebrafish mortality and increased doses. Detailed behavioral evaluations revealed a dose-dependent decrease in the speed and range of swimming, along with modifications in shoaling behavior, anxiety-like responses, and avoidance behaviors. Brain tissues transcriptomic analyses revealed the molecular responses underlying sub-chronic exposure to PLA-PBAT. Totally 702 DEGs and 5 KEGG pathways were significantly identified in low-dose group, with the top 2 significant pathways being ribosome pathway and cytokine-cytokine receptor interaction pathway. Totally 650 DEGs and 5 KEGG pathways were significantly identified in medium-dose group, with the top 2 significant pathways being Herpes simplex virus 1 infection pathway and complement and coagulation cascades pathway. Totally 1778 DEGs and 16 KEGG pathways were significantly identified in high-dose group, with the top 2 significant pathways being metabolism of xenobiotics by cytochrome P450 and drug metabolism - cytochrome P450 pathway. Most significantly enriched pathways are associated with immune responses. The validation of key gene in cytokine-cytokine receptor interaction pathway also confirmed its high correlation with behavioral indicators. These results indicate that PLA-PBAT is likely to cause behavioral abnormalities in zebrafish by triggering immune dysregulation in the brain.

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy.

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based disease modeling and drug assessment primarily operated at the cellular level, recent years have witnessed a significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling the observation of disease progression and drug metabolism in an in vivo-like environment, surpassing the capabilities of iPSC-derived cells. Furthermore, iPSC-based cell therapy has emerged as a focal point of clinical interest. In this review, we provide an extensive overview of non-integrative reprogramming methods that have evolved since the inception of iPSC technology. We also deliver a comprehensive examination of iPSC-derived organoids, spanning the realms of the nervous system, cardiovascular system, and oncology, as well as systematically elucidate recent advancements in iPSC-related cell therapies.

Low-Toxicity and High-Efficiency Streptomyces Genome Editing Tool Based on the Miniature Type V-F CRISPR/Cas Nuclease AsCas12f1.

Genome editing tools based on SpCas9 and FnCpf1 have facilitated strain improvements for natural product production and novel drug discovery in Streptomyces. However, due to high toxicity, their editing requires high DNA transformation efficiency, which is unavailable in most streptomycetes. The transformation efficiency of an all-in-one editing tool based on miniature Cas nuclease AsCas12f1 was significantly higher than those of SpCas9 and FnCpf1 in tested streptomycetes, which is due to its small size and weak DNA cleavage activity. Using this tool, in Streptomyces coelicolor, we achieved 100% efficiency for single gene or gene cluster deletion and 46.7 and 40% efficiency for simultaneous deletion of two genes and two gene clusters, respectively. AsCas12f1 was successfully extended to Streptomyces hygroscopicus SIPI-054 for efficient genome editing, in which SpCas9/FnCpf1 does not work well. Collectively, this work offers a low-toxicity, high-efficiency genome editing tool for streptomycetes, particularly those with low DNA transformation efficiency.