Encapsulation and release of tetrabromobisphenol A in microplastics: Trade-off in their individual toxicity to Xenopus tropicalis tadpoles.

The toxicity of microplastics (MPs) to aquatic animals is closely related to the presence and release kinetics of contained additives, as most plastic products contain various additives. However, the relationship between the occurrence and release of additives from MPs, and their individual or combined toxicity remains unclear. In this study, the nanoscale distribution and release of tetrabromobisphenol A (TBBPA, a common flame retardant with endocrine-disrupting effect) in polystyrene (PS) MPs, and the long-term (60 days) toxicity of TBBPA and MPs containing TBBPA (at doses of 0 %, 1 %, 10 %, w/w) to Xenopus tropicalis tadpoles were investigated. Exposure to 10 µg/L TBBPA alone was the most toxics, while the encapsulation of TBBPA in MPs significantly delayed its lethal toxicity to tadpoles by inhibiting the rapid and extensive release of TBBPA. PS MPs alone and MPs containing 10 % TBBPA exhibited delayed survival toxicity compared to TBBPA alone, whereas PS MPs containing 1 % TBBPA did not show this effect but inhibited growth. These findings suggest that chronic toxicity assessments should be based on long-term (months or even years) exposure experiments due to the encapsulation-controlled slow release of toxic additives.

Genetic Manifestations and Phenotype Spectrum in Infants With Feeding Difficulty.

BACKGROUND: Feeding difficulties frequently co-occur with multisystem disorders attributed to rare genetic diseases. In this study, we aimed to describe the genetic manifestations and phenotype spectrum in infants experiencing feeding difficulties. METHODS: This case series included infants under 6 months old with feeding difficulties admitted to the neonatal department of Children's Hospital, Zhejiang University School of Medicine from October 2018 to May 2022. All infants underwent whole-exome sequencing (WES) during hospitalisation, and their clinical phenotypes and genetic results were analyzed. RESULTS: Among 28 infants studied, nine were preterm and 19 were full-term. Median admission age was 13.5 days (IQR 6.5, 35), with a median hospital stay of 16 days (IQR 10.5, 30). Overall, 12 (42.9%) cases were complicated with multiple malformations. Abnormal muscle tone (53.6%) and neurological issues (42.9%) were notable prevalent in these infants. Cranial MR abnormalities were noted in 96.2% of cases. Based on the combined analysis of WES results and clinical phenotypes, a total of 22 (78.3%) patients displayed disease-related genetic variation identified through WES; among them, 15 (53.6%) patients received genetic diagnoses, while 7 (25%) patients were suspected diagnoses. Positive findings were more frequent in full-term (89.5%) than preterm infants (55.6%). Ultimately, 24 (85.7%) patients were discharged alive, with 75% requiring post-discharge tube feeding. Following discharge, five patients developed new symptoms linked to genetic variants, and two patients died. CONCLUSIONS: Feeding difficulty may constitute a facet of the phenotypic spectrum of rare genetic diseases. Whole-exome sequencing can enhance molecular diagnosis accuracy for infants with feeding difficulties.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer.

BACKGROUND AND PURPOSE: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). METHODS: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. RESULTS: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. CONCLUSION: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

Effect of Short-term Deep Breathing Exercises on Perioperative Anxiety and Pain in Pediatric Orthopedic Patients: A Randomized Controlled Trial.

PURPOSE: There are currently no pediatric studies examining the effects of deep breathing on perioperative pain and anxiety. This study sought to determine the effect of short-term deep breathing exercises on perioperative anxiety and pain in pediatric patients and their parents. DESIGN: A randomized controlled trial was conducted in the Department of Orthopaedic Surgery where pediatric patients about to undergo surgery were allocated to a control group or a deep breathing group. In the intervention group, patients and their main guardian were guided to practice 10 minutes of deep breathing exercises twice a day for 3 to 4 days prior to surgery. Perioperative anxiety and pain were measured for both the children and parents as outcome indicators. METHODS: Perioperative anxiety was measured using the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) and state anxiety was measured using the State-Trait Anxiety Inventory (STAI). Patients reported their pain levels daily using the Wong-Baker FACES Pain Rating Scale. The following cutoffs were determined as high levels of anxiety: STAI (adult) > 44, STAI (child) > 36, and mYPAS-SF ≥ 30. FINDINGS: No significant differences were found in the STAI, mYPAS-SF, and Wong-Baker FACES Pain Rating Scale scores of the patients between the intervention and control group. Overall statistics showed that parents had significantly higher postoperative state anxiety levels toward female children (44.93 ± 9.01) compared to male children (40.18 ± 9.89). Preoperative and postoperative parental state anxiety levels were correlated with the child's postoperative anxiety. Furthermore, children's postoperative state anxiety was slightly correlated with postoperative pain. CONCLUSIONS: Short-term use of our deep breathing exercises was ineffective in reducing incidences of perioperative pain and anxiety in pediatric orthopedic patients. A longer period of deep breathing administration may be required for the intervention to be effective. Parental anxiety may have an effect on anxiety levels in children, and postoperative parental anxiety may be affected by the gender of the child.

High-Throughput Screening for Oligonucleotide Detection by ADE-OPI-MS.

Oligonucleotides represent a class of shorter DNA or RNA nucleic acid polymers extensively applied in the biomedical field. Despite progress in detecting and analyzing oligonucleotides, high-throughput analysis of the samples remains challenging. In this work, a high-throughput analysis method for oligonucleotide analysis was developed based on acoustic droplet ejection-open port interface-mass spectrometry (ADE-OPI-MS) technology. This approach was applied to determine the enzymatic activity of terminal deoxynucleotide transferase (TdT) for DNA synthesis, with a rate of 3 s/sample, which enhanced single-sample analysis efficiency approximately 60-fold over the previous gel analysis. After testing approximately 10,000 TdT mutants, we obtained three new variants with higher catalytic activities. Finally, by integrating these mutants, the catalytic activity of TdT was improved about 4 times compared to the starting mutant. Our results successfully established a high-throughput screening method for oligonucleotide analysis, which not only provides a foundation to engineer highly efficient TdT for ab initio synthesis of DNA but also paves the way for the potential application of oligonucleotide analysis in biomedical fields.

Characterization of a novel multifunctional glycoside hydrolase family in the metagenome-assembled genomes of horse gut.

The gut microbiota is a treasure trove of carbohydrate-active enzymes (CAZymes). To explore novel and efficient CAZymes, we analyzed the 4,142 metagenome-assembled genomes (MAGs) of the horse gut microbiota and found the MAG117.bin13 genome (Bacteroides fragilis) contains the highest number of polysaccharide utilisation loci sites (PULs), indicating its high capability for carbohydrate degradation. Bioinformatics analysis indicate that the PULs region of the MAG117.bin13 genome encodes many hypothetical proteins, which are important sources for exploring novel CAZymes. Interestingly, we discovered a hypothetical protein (595 amino acids). This protein exhibits potential CAZymes activity and has a lower similarity to CAZymes, we named it BfLac2275. We purified the protein using prokaryotic expression technology and studied its enzymatic function. The hydrolysis experiment of the polysaccharide substrate showed that the BfLac2275 protein has the ability to degrade α-lactose (156.94 U/mg), maltose (92.59 U/mg), raffinose (86.81 U/mg), and hyaluronic acid (5.71 U/mg). The enzyme activity is optimal at pH 5.0 and 30 ℃, indicating that the hypothetical protein BfLac2275 is a novel and multifunctional CAZymes in the glycoside hydrolases (GHs). These properties indicate that BfLac2275 has broad application prospects in many fields such as plant polysaccharide decomposition, food industry, animal feed additives and enzyme preparations. This study not only serves as a reference for exploring novel CAZymes encoded by gut microbiota but also provides an example for further studying the functional annotation of hypothetical genes in metagenomic assembly genomes.

Association between sleep duration, suicidal ideation, suicidal attempt and suicidal behavior among Chinese adolescents.

BACKGROUND: A relatively small number of studies have researched the relationship between sleep duration and suicidal ideation, attempts, and behavior. This research aims to investigate the link between sleep duration and suicide in Chinese adolescents, and to examine the role of depression as a mediating factor. METHOD: Data were collected from 3315 students using a multi-stage random cluster sampling method and self-administered questionnaires. The study applied logistic regression to investigate the relationship between sleep duration and various forms of suicidal behavior, and mediation analysis to understand how depression might influence this relationship. RESULTS: The average sleep duration among the adolescents was 7.25 h (±0.20), with 59.67 % reporting insufficient sleep. The logistic regression analysis showed that longer sleep duration is linked with lower risks of suicidal ideation (OR: 0.753, 95%CI: 0.696 to 0.814), suicidal attempts (OR: 0.830, 95%CI: 0.748 to 0.922), and suicidal behavior (OR: 0.841, 95%CI: 0.713 to 0.992). Analysis using restricted cubic spline plots indicated the connection between sleep duration and these suicidal factors was not linear. The study found that depression plays a partial mediating role between sleep duration and suicidal ideation, with an effect of 52.29 %. LIMITATIONS: The cross-sectional study design could not prove causation. CONCLUSIONS: There is a clear non-linear association between sleep duration and suicidal tendencies in adolescents, with depression acting as a mediator. This suggests that future research could focus on sleep and mood management as ways to address suicide risk in this age group.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane.

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.

Immune Dysfunction-Associated Elevated RDW, APACHE-II, and SOFA Scores Were a Possible Cause of 28-Day Mortality in Sepsis Patients.

Objective: To explore the early predictors and their predicting value of 28-day mortality in sepsis patients and to investigate the possible causes of death. Methods: 127 sepsis patients were included, including 79 cases in the survival group and 48 cases in the death group. The results of all patients on admission were recorded. After screening the risk factors of 28-day mortality, the receiver operating characteristic curve (ROC) was used to determine their predictive value for the 28-day mortality rate on admission, and the Kaplan-Meier curve was drawn to compare the 28-day mortality rate between groups. Finally, patients with cytokine and lymphocyte subsets results were included for investigating the possible causes of death through correlation analysis. Results: APACHE II (acute physiology and chronic health evaluation II), SOFA (Sequential Organ Failure Assessment) and red blood cell distribution width (RDW) were the risk factors for 28-day mortality in sepsis patients (OR: 1.130 vs.1.160 vs.1.530, P < 0.05). The area under the curve (AUC), sensitivity and specificity of APACHE II, SOFA and RDW in predicting the mortality rate at 28 days after admission in sepsis patients were 0.763 vs 0.806 vs 0.723, 79.2% vs 68.8% vs 75.0%, 65.8% vs 89.9% vs 68.4%. The combined predicted AUC was 0.873, the sensitivity was 89.6%, and the specificity was 82.3%. The Kaplan-Meier survival curve showed that the 28-day mortality rates of sepsis patients with APACHE II≥18.5, SOFA≥11.5 and RDW≥13.8 were 58.5%, 80.5% and 59.0%, respectively. In the death group, APACHE II was positively correlated with SOFA, IL-2, and IL-10, and RDW was positively correlated with PLT, TNF-α, CD3+ lymphocyte count, and CD8+ lymphocyte count. Conclusion: Sepsis patients with high APACHE II, SOFA and RDW levels at admission have an increased 28-day mortality rate. The elevation of these indicators in dead patients are related to immune dysfunction.

High-Temperature Tolerance Protein Engineering through Deep Evolution.

Protein engineering aimed at increasing temperature tolerance through iterative mutagenesis and high-throughput screening is often labor-intensive. Here, we developed a deep evolution (DeepEvo) strategy to engineer protein high-temperature tolerance by generating and selecting functional sequences using deep learning models. Drawing inspiration from the concept of evolution, we constructed a high-temperature tolerance selector based on a protein language model, acting as selective pressure in the high-dimensional latent spaces of protein sequences to enrich those with high-temperature tolerance. Simultaneously, we developed a variant generator using a generative adversarial network to produce protein sequence variants containing the desired function. Afterward, the iterative process involving the generator and selector was executed to accumulate high-temperature tolerance traits. We experimentally tested this approach on the model protein glyceraldehyde 3-phosphate dehydrogenase, obtaining 8 variants with high-temperature tolerance from just 30 generated sequences, achieving a success rate of over 26%, demonstrating the high efficiency of DeepEvo in engineering protein high-temperature tolerance.

Skeleton-derived extracellular vesicles in bone and whole-body aging: From mechanisms to potential applications.

The skeleton serves as a supportive and protective organ for the body. As individuals age, their bone tissue undergoes structural, cellular, and molecular changes, including the accumulation of senescent cells. Extracellular vesicles (EVs) play a crucial role in aging through the cellular secretome and have been found to induce or accelerate age-related dysfunction in bones and to contribute further via the circulatory system to the aging of phenotypes of other bodily systems. However, the extent of these effects and their underlying mechanisms remain unclear. Therefore, this paper attempts to give an overview of the current understanding of age-related alteration in EVs derived from bones. The role of EVs in mediating communications among bone-related cells and other body parts is discussed, and the significance of bones in the whole-body aging process is highlighted. Ultimately, it is hoped that gaining a clearer understanding of the relationship between EVs and aging mechanisms may serve as a basis for new treatment strategies for age-related degenerative diseases in the skeleton and other systems.

Phthalocyanine blue leaching and exposure effects on Microcystis aeruginosa (cyanobacteria) of photoaged microplastics.

Light-stabilizing additives may contribute to the overall pollution load of microplastics (MPs) and potentially enter the food chain, severely threatening aquatic life and human health. This study investigated the variation between polystyrene (PS) MPs and phthalocyanine blue (CuPC)-containing MPs before and after photoaging, as well as their effects on Microcystis aeruginosa. The presence of PS-MPs increased cell mortality, antioxidant enzyme activity, and the variation in extracellular components, while the presence of CuPC exacerbated these variations. CuPC-containing MPs caused different increasing trends in superoxide dismutase and malondialdehyde activities due to electron transfer across the membrane. Transcriptomic analysis revealed that the MPs and CuPC affected various cellular processes, with the greatest impact being on cell membranes. Compared with MPs, CuPC negatively affected ribosome and polysaccharide formation. These findings provide insights into the molecular mechanisms underlying the cellular response to MPs and their associated light-stabilizer pollution and imply the necessity for mitigating the pollution of both MPs and light-stabilizers.

Stress-induced hyperglycemia is associated with the mortality of thrombotic thrombocytopenic purpura patients.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy with a rapid progression and high mortality rate. We aimed to explore early risk factors for mortality in patients with TTP. METHODS: We conducted a retrospective analysis of 42 TTP patients that were admitted to our hospital between 2000 and 2021, with a median age of 49 (29-63) years. Risk factors for mortality were evaluated using multivariate logistic regression. Receiver operating characteristic curve analysis was used to determine the cut-off value of glucose for predicting mortality in patients, which was validated by comparison to a similar cohort in the published literature. RESULTS: Elevated glucose level and reduced red blood cells (RBC) counts were risk factors for mortality in patients with TTP (glucose, odds ratio and 95% confidence interval: 2.476 [1.368-4.484]; RBC, odds ratio and 95% confidence interval: 0.095 [0.011-0.799]). The area under the curve of glucose was 0.827, and the cut-off value was 9.2 mmol/L, with a sensitivity of 75.0% and specificity of 95.8%. A total of 26 cases from the validation cohort had a sensitivity of 71.0% and a specificity of 84.0%. The change trends of the TTP-related laboratory indices differed during hospitalization. CONCLUSION: Hyperglycemia at admission and unstable blood glucose levels during hospitalization may be potential predictors of mortality for TTP patients. The improved prognosis was associated with the recovery of platelet counts and a significant decrease in serum lactate dehydrogenase after five days of treatment.

Development of Murine Anterior Interbody and Posterolateral Spinal Fusion Techniques.

BACKGROUND: Multiple animal models have previously been utilized to investigate anterior fusion techniques, but a mouse model has yet to be developed. The purpose of this study was to develop murine anterior interbody and posterolateral fusion techniques. METHODS: Mice underwent either anterior interbody or posterolateral spinal fusion. A protocol was developed for both procedures, including a description of the relevant anatomy. Samples were subjected to micro-computed tomography to assess fusion success and underwent biomechanical testing with use of 4-point bending. Lastly, samples were fixed and embedded for histologic evaluation. RESULTS: Surgical techniques for anterior interbody and posterolateral fusion were developed. The fusion rate was 83.3% in the anterior interbody model and 100% in the posterolateral model. Compared with a control, the posterolateral model exhibited a greater elastic modulus. Histologic analysis demonstrated endochondral ossification between bridging segments, further confirming the fusion efficacy in both models. CONCLUSIONS: The murine anterior interbody and posterolateral fusion models are efficacious and provide an ideal platform for studying the molecular and cellular mechanisms mediating spinal fusion. CLINICAL RELEVANCE: Given the extensive genetic tools available in murine disease models, use of fusion models such as ours can enable determination of the underlying genetic pathways involved in spinal fusion.

Deterioration of single-use biodegradable plastics in high-humidity air and freshwaters over one year: Significant disparities in surface physicochemical characteristics and degradation rates.

More single-use plastics are accumulating in the environment, and likewise biodegradable plastics (BPs), which are being vigorously promoted, cannot escape the fate. Currently, studies on the actual degradation of BPs in open-air and freshwaters are underrepresented despite they are potentially headmost leakage and contamination sites for disposable BPs. Herein, we compared the degradation behavior of six BP materials and non-degradable polypropylene (PP) plastics over a 1-year in situ suspension in the high-humidity air, a eutrophic river, and an oligotrophic lake. Moreover, a 3-months laboratory incubation was performed to detect the release of dissolved organic carbon (DOC) from BPs. In both air and freshwaters, poly(p-dioxanone) (PPDO) degraded significantly while PP and polylactic acid (PLA) showed no signs of degradation. The average degradation rates of three poly(butylene adipate-co-terephthalate) (PBAT)-based films varied: 100% in river, 55% in lake, and 10% in air. In addition to PLA, surface chemical groups, hydrophilicity, and thermal stability of BPs changed, and microplastics were found on their surfaces. Correspondingly, BPs with faster degradation rates released relatively higher amounts of DOC. Environmental microbial and chemical characteristics may contribute to differences in BP degradation besides polymer specificity. Altogether, our results indicate the need for appropriate monitoring of BPs.

Deep convolutional neural networks for aged microplastics identification by Fourier transform infrared spectra classification.

Infrared (IR) spectroscopy is a powerful technique for detecting and identifying Microplastics (MPs) in the environment. However, the aging of MPs presents a challenge in accurately identification and classification. To address this challenge, a classification model based on deep convolutional neural networks (CNNs) was developed using infrared spectra results. Particularly, original infrared (IR) spectra were used as the sample dataset, therefore, relevant spectral details were preserved and additional noise or distortions were not introduced. The Adam (Adaptive moment estimation) algorithm was employed to accelerate gradient descent and weight update, the Dropout function was implemented to prevent overfitting and enhance the generalization performance of the network. An activation function ReLu (Rectified Linear Unit) was also utilized to simplify the co-adaptation relationship among neurons and prevent gradient disappearance. The performance of the CNN model in MPs classification was evaluated based on accuracy and robustness, and compared with other machine learning techniques. CNN model demonstrated superior capabilities in feature extraction and recognition, and greatly simplified the pre-processing procedure. The identification results of aged commercial microplastic samples showed accuracies of 40 % for Artificial Neural Network, 60 % for Random Forest, 80 % for Deep Neural Network, and 100 % for CNN, respectively. The CNN architecture developed in this work also demonstrates versatility by being suitable for both limited data cases and potential expansion to include more discrete data in the future.

Effect of C-reactive protein deficiency on insulin resistance reversal in rats with polycystic ovary syndrome through augmented leptin action.

BACKGROUND: C-reactive protein(CRP), is an inflammatory marker that weaken leptin bioavailability and insulin sensitivity to disturb energy and glucose metabolism. Polycystic ovary syndrome (PCOS) exhibit a metabolic component consisting of higher plasma CRP levels, hyperinsulinemic and hyperleptinemia. The ability of leptin to regulation of hepatic glucose production (HGP) in the absence of CRP in PCOS remain unknown. METHODS: Dehydroepiandrosterone (DHEA) was used to induce PCOS in rats. We assessed the effects of CRP gene knockout in PCOS model rats on body weight, energy expenditure glucose metabolism and insulin sensitivity. We conducted experiments involving the administration of leptin to both the peripheral and central systems in PCOS model rats with CRP knockout, and studied the effects on changes in glucose kinetics during hyperinsulinemic-euglycemic clamps. RESULTS: In female PCOS rats, the lack of CRP resulted in decreased leptin resistance and weight gain, increased energy expenditure, and improved insulin sensitivity. Additionally, the deletion of the CRP gene strengthened the HGP-lowering effects of leptin when administered peripherally or centrally. This effect was accompanied by a decrease in the expression of hepatic gluconeogenic enzymes and an increase in hepatic insulin signaling. Finally, inhibition of glucose production was also enhanced for central leptin administration during lipid infusion in PCOS rats. CONCLUSIONS: Our findings highlight the therapeutic potential of targeting CRP to restore glucose homeostasis and insulin sensitivity for leptin in PCOS.

A multi-stem cell basis for craniosynostosis and calvarial mineralization.

Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in craniosynostosis remains poorly understood. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a previously identified cathepsin K (CTSK) lineage CSC1 (CTSK+ CSC) and a separate discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2+ CSC) that we identified in this study. Deletion of Twist1, a gene associated with craniosynostosis in humans2,3, solely in CTSK+ CSCs is sufficient to drive craniosynostosis in mice, but the sites that are destined to fuse exhibit an unexpected depletion of CTSK+ CSCs and a corresponding expansion of DDR2+ CSCs, with DDR2+ CSC expansion being a direct maladaptive response to CTSK+ CSC depletion. DDR2+ CSCs display full stemness features, and our results establish the presence of two distinct stem cell lineages in the sutures, with both populations contributing to physiologic calvarial mineralization. DDR2+ CSCs mediate a distinct form of endochondral ossification without the typical haematopoietic marrow formation. Implantation of DDR2+ CSCs into suture sites is sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK+ CSCs. Finally, the human counterparts of DDR2+ CSCs and CTSK+ CSCs display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface for the modulation of calvarial mineralization and suture patency.

A vertebral skeletal stem cell lineage driving metastasis.

Vertebral bone is subject to a distinct set of disease processes from long bones, including a much higher rate of solid tumour metastases1-4. The basis for this distinct biology of vertebral bone has so far remained unknown. Here we identify a vertebral skeletal stem cell (vSSC) that co-expresses ZIC1 and PAX1 together with additional cell surface markers. vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. vSSCs are physiologic mediators of vertebral bone formation, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness features. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed in breast cancer, owing in part to increased secretion of the novel metastatic trophic factor MFGE8. Together, our results indicate that vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of vertebral metastasis.

Accelerated Catalytic Ozonation in a Mesoporous Carbon-Supported Atomic Fe-N4 Sites Nanoreactor: Confinement Effect and Resistance to Poisoning.

The design of a micro-/nanoreactor is of great significance for catalytic ozonation, which can achieve effective mass transfer and expose powerful reaction species. Herein, the mesoporous carbon with atomic Fe-N4 sites embedded in the ordered carbon nanochannels (Fe-N4/CMK-3) was synthesized by the hard-template method. Fe-N4/CMK-3 can be employed as nanoreactors with preferred electronic and geometric catalytic microenvironments for the internal catalytic ozonation of CH3SH. During the CH3SH oxidation process, the mass transfer coefficient of the Fe-N4/CMK-3 confined system with sufficient O3 transfer featured a level of at least 1.87 × 10-5, which is 34.6 times that of the Fe-N4/C-Si unconfined system. Detailed experimental studies and theoretical calculations demonstrated that the anchored atomic Fe-N4 sites and nanoconfinement effects regulated the local electronic structure of the catalyst and promoted the activation of O3 molecules to produce atomic oxygen species (AOS) and reactive oxygen species (ROS), eventually achieving efficient oxidation of CH3SH into CO2/SO42-. Benefiting from the high diffusion rate and the augmentation of AOS/ROS, Fe-N4/CMK-3 exhibited an excellent poisoning tolerance, along with high catalytic durability. This contribution provides the proof-of-concept strategy for accelerating catalytic ozonation of sulfur-containing volatile organic compounds (VOCs) by combining confined catalysis and atomic catalysts and can be extended to the purification of other gaseous pollutants.