Fulvic acid enhanced peroxymonosulfate activation over Co-Fe binary metals for efficient degradation of emerging bisphenols.

Bisphenol F (BPF) and bisphenol S (BPS) are emerging bisphenols, which have become the main substitutes for bisphenol A (BPA) in industrial production and are also considered as new environmental pollution challenges. Thus, the necessity for an effective approach to remove BPF and BPS is essential. In this study, fulvic acid (FA) was used to modify Co-Fe binary metals (CFO) for peroxymonosulfate (PMS) activation. The characterization results demonstrated that CFO changed significantly in morphology after compounding with FA, with smaller particle size and 5.6 times larger specific surface area, greatly increasing the active sites of catalyst; Moreover, humic acid-like compounds increased the surface functional groups of CFO, especially phenolic hydroxyl, which could effectively prolong the PMS activation. The concentration of all reactive species, such as SO4•-, •OH, O2•-, and 1O2 increased in FA@CFO/PMS system. As a result, the degradation efficiency of CFO for both BPF and BPS was significantly improved after compounding FA, which also had a wide range of pH applications. The degradation pathways of both BPF and BPS were proposed based on liquid chromatography-mass spectrometry (LC-MS) analysis and the density functional theory (DFT) calculations. Our findings are expected to provide new strategies and methods for remediation of environmental pollution caused by emerging bisphenols.

Risk Factors Analysis for Different Types of Unfavorable Fracture Patterns During Sagittal Split Ramus Osteotomy: A Retrospective Study of 2008 Sides.

PURPOSE: To summarize unfavorable fracture patterns during sagittal split ramus osteotomy (SSRO) and investigate the association with influencing factors. MATERIALS AND METHODS: We conducted a retrospective analysis of 1007 patients with 2008 sides of SSRO and classified unfavorable fracture patterns into three types: fracture lines involving the sigmoid notch, condylar process, or coronoid process (Type A); fracture lines extending from the posterior border of the mandibular ramus to the mandibular body or the anterior border of the ramus (Type B); and unfavorable fractures located in the anterior horn of the proximal segment with free fragment (Type C). Logistic regression analysis was used to evaluate factors influencing unfavorable fracture patterns, including sex, age at the time of operation, class of occlusion, presence of the third molar, uni- or bi-maxillary surgery, and the distance from the mandibular canal to the buccal cortex. RESULTS: The distance from the mandibular canal to the buccal cortex was significantly associated with unfavorable fracture patterns during SSRO. The presence of third molars was significantly associated with Type A fractures. The distance from the mandibular canal to the buccal cortex was significantly lower in Type B fractures. CONCLUSION: We found that the influencing factors for unfavorable fracture patterns varied. Clinicians should pay specific attention to patients with factors for each unfavorable fracture pattern during SSRO. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Epidemic versus economic performances of the COVID-19 lockdown: A big data driven analysis.

Lockdown measures have been a "panacea" for pandemic control but also a violent "poison" for economies. Lockdown policies strongly restrict human mobility but mobility reduce does harm to economics. Governments meet a thorny problem in balancing the pros and cons of lockdown policies, but lack comprehensive and quantified guides. Based on millions of financial transaction records, and billions of mobility data, we tracked spatio-temporal business networks and human daily mobility, then proposed a high-resolution two-sided framework to assess the epidemiological performance and economic damage of different lockdown policies. We found that the pandemic duration under the strictest lockdown is less about two months than that under the lightest lockdown, which makes the strictest lockdown characterize both epidemiologically and economically efficient. Moreover, based on the two-sided model, we explored the spatial lockdown strategy. We argue that cutting off intercity commuting is significant in both epidemiological and economical aspects, and finally helped governments figure out the Pareto optimal solution set of lockdown strategy.

Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits and psychiatric symptoms. The gut microbiota-brain axis plays a pivotal role during AD development, which could target nutritional intervention. The prebiotic mannan oligosaccharide (MOS) has been reported to reshape the gut microbiome and enhanced the formation of the neuroprotective metabolites short-chain fatty acids (SCFAs). Here, we found that an 8-week treatment of MOS (0.12%, w/v in the drinking water) significantly improved cognitive function and spatial memory, accompanied by attenuated the anxiety- and obsessive-like behaviors in the 5xFAD transgenic AD mice model. MOS substantially reduced the Aß accumulation in the cortex, hippocampus, and amygdala of the brain. Importantly, MOS treatment significantly balanced the brain redox status and suppressed the neuroinflammatory responses. Moreover, MOS also alleviated the HPA-axis disorders by decreasing the levels of hormones corticosterone (CORT) and corticotropin-releasing hormone (CRH) and upregulated the norepinephrine (NE) expressions. Notably, the gut barrier integrity damage and the LPS leak were prevented by the MOS treatment. MOS re-constructed the gut microbiota composition, including increasing the relative abundance of Lactobacillus and reducing the relative abundance of Helicobacter. MOS enhanced the butyrate formation and related microbes levels. The correlation analysis indicated that the reshaped gut microbiome and enhanced butyrate formation are highly associated with behavioral alteration and brain oxidative status. SCFAs supplementation experiment also attenuated the behavioral disorders and Aß accumulation in the AD mice brain, accompanied by balanced HPA-axis and redox status. In conclusion, the present study indicated that MOS significantly attenuates the cognitive and mental deficits in the 5xFAD mice, which could be partly explained by the reshaped microbiome and enhanced SCFAs formation in the gut. MOS, as a prebiotics, can be translated into a novel microbiota-targeted approach for managing metabolic and neurodegenerative diseases.

Docetaxel-encapsulating small-sized polymeric micelles with higher permeability and its efficacy on the orthotopic transplantation model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance, and the small-sized nanocarrier loaded with platinum has been adopted to address this problem which is not suitable for loading docetaxel (DTX). In the present study, we used the poly(D,L-lactide)-b-polyethylene glycol-methoxy (mPEG-b-PDLLA) to encapsulate DTX and got a small-sized polymeric micelle (SPM); meanwhile we functionalized the SPM's surface with TAT peptide (TAT-PM) for a higher permeability. The diameters of both SPM and TAT-PM were in the range of 15-26 nm. In vitro experiments demonstrated that TAT-PM inhibited Capan-2 Luc PDAC cells growth more efficiently and induced more apoptosis compared to SPM and Duopafei. The in vivo therapeutic efficiencies of SPM and TAT-PM compared to free DTX was investigated on the orthotopic transplantation model of Capan-2 Luc. SPM exerted better therapeutic efficiency than free DTX, however, TAT-PM didn't outperformed SPM. Overall, these results disclosed that SPM could represent a new therapeutic approach against pancreatic cancer, but its permeability to PDAC was not the only decisive factor.

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge. The identification of reliable prognostic biomarkers and construction of an accurate prognostic model are crucial. Methods: In this study, mRNA expression data and clinical data of HNSCC patients from The Cancer Genome Atlas were used. Overlapping candidate genes (OCGs) were identified by intersecting differentially expressed genes and prognosis-related genes. Best prognostic genes were selected using the least absolute shrinkage and selection operator Cox regression based on OCGs, and a risk score was developed using the Cox coefficient of each gene. The prognostic power of the risk score was assessed using Kaplan-Meier survival analysis and time-dependent receiver operating characteristic analysis. Univariate and multivariate Cox regression were performed to identify independent prognostic parameters, which were used to construct a nomogram. The predictive accuracy of the nomogram was evaluated using calibration plots. Functional enrichment analysis of risk score related genes was performed to explore the potential biological functions and pathways. External validation was conducted using data from the Gene Expression Omnibus and ArrayExpress databases. Results: FADS3, TNFRSF12A, TJP3, and FUT6 were screened to be significantly related to prognosis in HNSCC patients. The risk score effectively stratified patients into high-risk group with poor overall survival (OS) and low-risk group with better OS. Risk score, age, clinical M stage and clinical N stage were regarded as independent prognostic parameters by Cox regression analysis and used to construct a nomogram. The nomogram performed well in 1-, 2-, 3-, 5- and 10-year survival predictions. Functional enrichment analysis suggested that tight junction was closely related to the cancer. In addition, the prognostic power of the risk score was validated by external datasets. Conclusions: This study constructed a gene-based model integrating clinical prognostic parameters to accurately predict prognosis in HNSCC patients.

Modeling long-term transfers of radiocesium in farmland under different tillage and cover crop treatments.

The 2011 nuclear accident at Japan's Fukushima Daiichi Nuclear Power Plant (FDNPP) prompted inquiries about the long-term transfer of Cesium-137 (137Cs) from soil to agricultural plants. In this context, numerical modeling is particularly useful for the long-term evaluation of the consequences of agroecosystem contamination. Agricultural practices, such as tillage and cover cropping, play key roles in 137Cs recycling in agroecosystems. In this study, we used 10-year monitoring data to develop a dynamic model to predict 137Cs redistribution (via uptake, litterfall, translocation, and percolation) under different tillage (no-tillage, NT; rotary cultivation, RC; moldboard plow, MP) and cover crop (rye; hairy vetch; fallow weed) treatments. The verification exercise and assessment results indicated the model's reliability, as the temporal dynamics of predicted values agreed with observed values. Tillage significantly influenced the 137Cs distribution in soil, thereby decreasing plant uptake of 137Cs, whereas cover crop exerted a minimal effect on 137Cs cycling. Furthermore, while the 137Cs concentrations in soybean grain under RC and NT treatments were comparable 62 years after the FDNPP accident, the concentration under MP treatment remained consistently the lowest. Despite natural decay being the main cause of the decreased global 137Cs level in the agroecosystem, with minimal losses from percolation to deeper soil layers and soybean harvesting, adopting an appropriate tillage practice was shown to promote a long-term reduction of 137Cs concentration in crops. Finally, to improve the model's accuracy, further research should consider incorporating the effects of soil properties and extreme weather events on 137Cs flow into the model, as these factors are essential for realizing improved agroecosystem predictions.

Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins.

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions. Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen "cryo-shock" strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety. Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice. Discussion: The results of this study demonstrate the potential of autologous "cryo-shocked" neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

Peptide S4 is an entry inhibitor of SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant socioeconomic burden, and combating COVID-19 is imperative. Blocking the SARS-CoV-2 RBD-ACE2 interaction is a promising therapeutic approach for viral infections, as SARS-CoV-2 binds to the ACE2 receptors of host cells via the RBD of spike proteins to infiltrate these cells. We used computer-aided drug design technology and cellular experiments to screen for peptide S4 with high affinity and specificity for the human ACE2 receptor through structural analysis of SARS-CoV-2 and ACE2 interactions. Cellular experiments revealed that peptide S4 effectively inhibited SARS-CoV-2 and HCoV-NL63 viruses from infecting host cells and was safe for cells at effective concentrations. Based on these findings, peptide S4 may be a potential pharmaceutical agent for clinical application in the treatment of the ongoing SARS-CoV-2 pandemic.

Generation of Hypoparathyroid Rats via Carbon-Nanoparticle-Assisted Parathyroidectomy.

Hypoparathyroidism (HypoPT) is a rare disease involving the parathyroid glands that is characterized by a reduced secretion or potency of the parathyroid hormone (PTH), which leads to high serum phosphorus levels and low serum calcium levels. HypoPT most commonly results from accidental damage to the glands or their removal during thyroid or other anterior neck surgery. Parathyroid/thyroid surgery has become more common in recent years, with a corresponding rise in the occurrence of HypoPT as a postoperative complication. There is a critical need for a HypoPT animal model to better understand the mechanisms underlying the effects of HypoPT on mineral ion homeostasis and to verify the therapeutic effectiveness of novel treatments. Here, a technique is reported to create acquired HypoPT in male rats by performing parathyroidectomy (PTX) using carbon nanoparticles. The rat model shows great promise over the mouse models of hypoparathyroidism. Importantly, the human PTH receptor binding region has an 84.2% sequence similarity with that of the rat, which is higher than the 73.7% similarity shared with mice. Moreover, the effects of estrogen, which can affect the PTH/PTHrP receptor signaling pathway, have not been fully investigated in male rats. Carbon nanoparticles are lymphatic tracers that stain the thyroid lymph nodes black without affecting their function, but they do not stain the parathyroid glands, which makes them easy to identify and remove. In this study, serum PTH levels were undetectable after PTX, and this resulted in significant hypocalcemia and hyperphosphatemia. Thus, the clinical state of postoperative HypoPT can be remarkably represented in the rat model. Carbon-nanoparticle-assisted PTX can, therefore, serve as an extraordinarily effective and readily implementable model for studying the pathogenesis, treatment, and prognosis of HypoPT.

Silver metallization-triggered liposome-embedded AIE fluorophore for dual-mode detection of biogenic amines to fight food freshness fraud.

To combat food freshness fraud, it is urgent to develop a method which could realize the detection of biogenic amines (BAs) present in food. In our study, we developed a colorimetric and ratiometric fluorescence dual-mode sensor which integrated with silver metallization-based response system of AIE liposome + OPD + RSM + Ag+ toward BAs in foods for fighting freshness fraud. With the hydrolysis from the alkaline of BAs to resorcinol monoacetate (RSM), the production resorcinol (RS) could metallize silver ion (Ag+) to silver atoms (Ag0) which could lead to a BAs concentration-dependent decrease of the oxidation product 2,3-diaminophenothiazine (DAP) of Ag+ to o-phenylenediamine (OPD). As a result, the dual-mode sensor has a low detection limit and wide linear range in the spiked detection of soy products, pork and milk samples for BAs. Thus, providing a reliable method for food safety and forestalling food freshness fraud.

Regulatory role of human fibrocartilage stem cells in condyle osteochondroma.

OBJECTIVE: Osteochondroma is a common benign skeletal disorder for which different molecular and histological features of long bones have been reported. We investigated cell-of-origin and molecular mechanisms of a rare condylar osteochondroma (CO). METHODS: Human fibrocartilage stem cells (hFCSCs) isolated from CO and normal condyle tissue were used for RNA sequencing, real-time PCR, Western Blotting, immunohistology, flowcytometry, as well as for chondrogenic differentiation, proliferation, and apoptosis detection assays. RESULTS: HFCSCs were fewer in number with weaker proliferative capacity and higher apoptosis ratio in the CO group. During the chondrogenic inducing process, hFCSCs from CO were prone to form more mature and hypertrophic cartilage. The result of RNA sequencing of hFCSCs from CO and normal condyle revealed a correlation between the PI3K/AKT signalling pathway and CO. Activated PI3K/AKT signalling might lead to functional changes in hFCSCs by enhancing cell apoptosis in the developmental process of CO. Increased expression of BCL2-like protein 11 (BIM) in CO tissue also supports this conclusion. Furthermore, the activation of the PI3K/AKT pathway in TMJ of mice induced histological disorder and increased apoptosis in condylar cartilage. CONCLUSION: We conclude that the activation of PI3K/AKT signalling in hFCSCs of CO suggests a new hypothesis for the cell-of-origin of human CO and another possible target to treat it.

The heteroaggregation behavior of nanoplastics on goethite: Effects of surface functionalization and solution chemistry.

Nanoplastics have attracted extensive attention in recent years. However, little is known about the heteroaggregation behavior of nanoplastics on goethite (FeOOH), especially the contribution of surface functional groups. In this study, the heteroaggregation behavior between polystyrene nanoplastics (PSNPs) and FeOOH was systematically investigated under different reaction conditions. Moreover, the effect of different functional groups (-NH2, -COOH, and bare) of PSNPs and solution chemistry was evaluated. The results showed that PSNPs could heteroaggregate with FeOOH, and the heteroaggregation rate of PSNPs with surface functionalization was significantly faster. The removal of suspended PSNPs was enhanced with increasing NaCl or CaCl2 concentration. However, heteroaggregation was significantly inhibited with the increase of solution pH. The zeta potentials analysis, time-resolved dynamic light scattering (DLS) and heteroaggregation experiments suggested that the electrostatic force affected the heteroaggregation process significantly. Fourier transform infrared (FTIR) spectra proved that the adsorption affinity between PSNPs and FeOOH was stronger after surface functionalization, especially for CH, O-C=O, and -CH2- groups, indicating that chemical bonding also made a contribution during the heteroaggregation process. This work is expected to provide a theoretical basis for predicting the environmental behavior between PSNPs and FeOOH.

Igf1 Regulates Fibrocartilage Stem Cells, Cartilage Growth, and Homeostasis in the Temporomandibular Joint of Mice.

Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER+ ; Tmflfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER+ ; Igf1fl/fl mice. In Gli1-CreER+ ; Tmflfl mice, red fluorescence+ (RFP+ ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1+ /Col2+ cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER+ ; Igf1fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1+ FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1+ -specific deletion of Igf1. In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).

A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury.

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11+ mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2+ non-chondrogenic fibroblasts instead of Chad+ chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

A Smart DNA-Based Nanosystem Containing Ribosome-Regulating siRNA for Enhanced mRNA Transfection.

Messenger RNA (mRNA) transfection is the prerequisite for the application of mRNA-based therapeutics. In hard-to-transfect cells, such as macrophages, the effective transfection of mRNA remains a long-standing challenge. Herein, a smart DNA-based nanosystem is reported containing ribosome biogenesis-promoting siRNA, realizing efficient mRNA transfection in macrophages. Four monomers are copolymerized to form a nanoframework (NF), including N-isopropylacrylamide (NIPAM) as the skeleton and acrydite-DNA as the initiator to trigger the cascade assembly of DNA hairpins (H1-polyT and H2-siRNA). By virtue of the phase transition characteristic of polymeric NIPAM, below the lower critical solution temperature (LCST, ≈34 °C), the NF swells to expose polyT sequences to hybridize with the polyA tail of mRNA. Above the LCST, the NF deswells to encapsulate mRNA. The disulfide bond in the NF responds to glutathione, triggering the disassembly of the nanosystem; the siRNA and mRNA are released in response to triphosadenine and RNase H. The siRNA down-regulates the expression of heat shock protein 27, which up-regulates the expression of phosphorylated ribosomal protein S6. The nanosystem shows satisfactory mRNA transfection and translation efficiency in a mouse model. It is envisioned that the DNA-based nanosystem will provide a promising carrier to deliver mRNA in hard-to-transfect cells and promote the development of mRNA-based therapeutics.

MobCovid: Confirmed Cases Dynamics Driven Time Series Prediction of Crowd in Urban Hotspot.

Monitoring the crowd in urban hot spot has been an important research topic in the field of urban management and has high social impact. It can allow more flexible allocation of public resources such as public transportation schedule adjustment and arrangement of police force. After 2020, because of the epidemic of COVID-19 virus, the public mobility pattern is deeply affected by the situation of epidemic as the physical close contact is the dominant way of infection. In this study, we propose a confirmed case-driven time-series prediction of crowd in urban hot spot named MobCovid. The model is a deviation of Informer, a popular time-serial prediction model proposed in 2021. The model takes both the number of nighttime staying people in downtown and confirmed cases of COVID-19 as input and predicts both the targets. In the current period of COVID, many areas and countries have relaxed the lockdown measures on public mobility. The outdoor travel of public is based on individual decision. Report of large amount of confirmed cases would restrict the public visitation of crowded downtown. But, still, government would publish some policies to try to intervene in the public mobility and control the spread of virus. For example, in Japan, there are no compulsory measures to force people to stay at home, but measures to persuade people to stay away from downtown area. Therefore, we also merge the encoding of policies on measures of mobility restriction made by government in the model to improve the precision. We use historical data of nighttime staying people in crowded downtown and confirmed cases of Tokyo and Osaka area as study case. Multiple times of comparison with other baselines including the original Informer model prove the effectiveness of our proposed method. We believe our work can make contribution to the current knowledge on forecasting the number of crowd in urban downtown during the Covid epidemic.

Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma.

BACKGROUND: Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches. METHODS: To obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single-cell RNA sequencing and T-cell/B-cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour-infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence in situ hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma. RESULTS: Promoting natural killer (NK) cell and CD8_GZMK T-cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2-like activity of tumour-associated macrophages (TAMs) could be an effective approach. Antigen-presenting cancer-associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen-presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro. CONCLUSION: Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.

Radiocesium distribution caused by tillage inversion affects the soil-to-crop transfer factor and translocation in agroecosystems.

This study reports the translocation of cesium-137 (137Cs) into deep soil layers, and the 137Cs transfer from soil to soybean in farmland under three tillage (no tillage, NT; rotary cultivation, RC; moldboard plow; MP) treatments and an undisturbed grassland (GL) at eight years after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident on 11 March 2011 in Japan. Tillage influences the 137Cs distribution in the 0-30 cm of soil; the distribution of 137Cs in the soil was uniform under RC and MP treatments, while in the grassland, most 137Cs was concentrated on the soil surface (0-2.5 cm). The center of vertical 137Cs radioactivity concentration (the thickness of the soil from surface which containing half of the 137Cs inventory) in GL was 5.5 cm, which was shallower than that in farmland (9.5 cm in NT, 13.6 cm in RC and 15.2 cm in MP). Hence, the total translocation distance of 137Cs 8 years after FDNPP accident showed the following trend: GL (2.4 cm) < NT (7.0 cm) < RC (10.0 cm) < MP (12.3 cm). Meanwhile, a significant positive correlation was observed between 137Cs radioactivity concentration and organic carbon and nitrogen content in the soil. However, the 137Cs radioactivity concentration in soybean grains was negatively correlated with the center of vertical 137Cs radioactivity concentration but positively correlated with the ratio of exchangeable 137Cs (ExCs) and K content in the soil. The ExCs/K and 137Cs distributions in the soil were combined into a statistical model to predict the 137Cs radioactivity concentration in soybean grain. The results revealed the magnitude of the impact of 137Cs distribution on the 137Cs transfer from soil to crop. The addition of the 137Cs distribution dramatically improved the accuracy of the prediction model of 137Cs radioactivity concentration in soybean.

Biodegradable Inks in Indirect Three-Dimensional Bioprinting for Tissue Vascularization.

Mature vasculature is important for the survival of bioengineered tissue constructs, both in vivo and in vitro; however, the fabrication of fully vascularized tissue constructs remains a great challenge in tissue engineering. Indirect three-dimensional (3D) bioprinting refers to a 3D printing technique that can rapidly fabricate scaffolds with controllable internal pores, cavities, and channels through the use of sacrificial molds. It has attracted much attention in recent years owing to its ability to create complex vascular network-like channels through thick tissue constructs while maintaining endothelial cell activity. Biodegradable materials play a crucial role in tissue engineering. Scaffolds made of biodegradable materials act as temporary templates, interact with cells, integrate with native tissues, and affect the results of tissue remodeling. Biodegradable ink selection, especially the choice of scaffold and sacrificial materials in indirect 3D bioprinting, has been the focus of several recent studies. The major objective of this review is to summarize the basic characteristics of biodegradable materials commonly used in indirect 3D bioprinting for vascularization, and to address recent advances in applying this technique to the vascularization of different tissues. Furthermore, the review describes how indirect 3D bioprinting creates blood vessels and vascularized tissue constructs by introducing the methodology and biodegradable ink selection. With the continuous improvement of biodegradable materials in the future, indirect 3D bioprinting will make further contributions to the development of this field.