Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits Melanoma Growth.

It is difficult to obtain specific tumor antigens, which is one of the main obstacles in the development of tumor vaccines. The vaccines containing multivalent antigens are thought to be more effective in antitumor therapy. In this study, a mRNA encoding three neoantigens of melanoma were prepared and encapsulated into the mannosylated chitosan-modified ethosomes (EthsMC) to obtain a multivalent mRNA vaccine (MmRV) for transcutaneous immunization (TCI). MmRV can effectively induce maturation of dendritic cells, with a better performance than mRNA of a single neoantigen. TCI patches (TCIPs) loading MmRV or siRNA against PDL1 (siPDL1) were prepared and applied to the skin of melanoma-bearing mice. The results showed that TCIPs significantly increase the levels of TNF-α, IFN-γ, and IL-12 in both plasma and tumor tissues, inhibit tumor growth, as well as promote infiltration of CD4+ and CD8+ T cells in the tumor tissues. Furthermore, the combination of MmRV and siPDL1 showed much better antitumor effects than either monotherapy, suggesting a synergistic effect between the vaccine and PDL1 blocker. In addition, the treatment with the TCIPs did not cause damage to the skin, blood, and vital organs of the mice, showing good biosafety. To the best of our knowledge, this work is the first to construct a noninvasive TCI system containing MmRV and siPDL1, providing a convenient and promising approach for tumor treatment.

Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma: an open-label, multicenter, phase 1 study (MMY1010).

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

A novel antibiotic: the antimicrobial effects of CFBSA and its application on electronspun wound dressing.

N-chloro-N-fluorobenzenesulfonylamide (CFBSA), was a novel chlorinating reagent, which exhibits potential antibacterial activities. In this study, CFBSA was confirmed as a wide-broad antimicrobial and bactericidal drug against different gram-negative bacteria, gram-positive bacteria and fungi, while it was found to have low cytotoxicity for eukaryotic cells. In addition, microorganism morphology assay and oxidative stress test was used to determine the antimicrobial mechanisms of CFBSA. According to the results, CFBSA probably had a target on cell membrane and killed microorganism by disrupting its cell membrane. Then, CFBSA was first combined with PLCL/SF via electrospinning and applied in wound dressings. The characterization of different PLCL/SF of CFBSA-loaded nanofibrous mats was investigated by SEM, water contact angle, FTIR, cell compatibility and antimicrobial test. CFBSA-loaded PLCL/SF nanofibrous mats showed excellent antimicrobial activities. In order to balance of the biocompatibility and antibacterial efficiency, SP-2.5 was selected as the ideal loading concentration for further application of CFBSA-loaded PLCL/SF. In conclusion, the electrospun CFBSA-loaded PLCL/SF nanofibrous mat with its broad-spectrum antimicrobial and bactericidal activity and good biocompatibility showed enormous potential for wound dressing.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

Transformation of 6:6 PFPiA in the gut of Xenopus laevis: Synergistic effects of CYP450 enzymes and gut microflora.

As a frequently detected per- and polyfluoroalkyl substance in the environment, 6:6 perfluoroalkylhypophosphinic acid (6:6 PFPiA) is vulnerable to transformation in the liver of organisms, but the transformation in gut is still unclear. This study investigates the molecular mechanisms of 6:6 PFPiA transformation in the gut of Xenopus laevis upon a 28-day exposure in water. Before Day 16, a notable correlation (p = 0.03) was observed between the transformation product (PFHxPA) and cytochrome P450 (CYP450) enzyme concentration in gut. This suggests that CYP450 enzymes played an important role in the transformation of 6:6 PFPiA in the gut, which was verified by an in vitro incubation with gut tissues, and supported by the molecular docking results of 6:6 PFPiA binding with CYP450 enzymes. From the day 16, the CYP450 concentration in gut decreased by 31.3 % due to the damage caused by 6:6 PFPiA, leading to a decrease in the transformation capacity in gut, but the transformation rate was stronger than in liver. This was in contrast with the in vitro experiment, where transformation was stronger in liver. In the mean time, the abundance of Bacteroidota in gut increased, which released hydrolytic enzyme and then could participate in the transformation as well. This study reveals the potential of the gut in metabolizing environmental pollutants, and provides profound insights into the potential health risks caused by 6:6 PFPiA in organisms.

Novel insights into intrinsic mechanisms of magnetic field on long-term performance of anaerobic ammonium oxidation process.

The performance of an anaerobic ammonium oxidation (anammox) reactor with the magnetic field of 40 mT was systematically investigated. The total nitrogen removal rate was enhanced by 16% compared with that of the control group. The enhancing mechanism was elucidated from the improved mass transfer efficiency, the complicated symbiotic interspecific relationship and the improved levels of functional genes. The magnetic field promoted formation of the loose anammox granular sludge and the homogeneous and well-connected porous structure to enhance the mass transfer. Consequently, Candidatus Brocadia predominated in the sludge with an increase in abundance of 13%. Network analysis showed that the positive interactions between Candidatus Brocadia and heterotrophic bacteria were strengthened, which established a more complicated stable microbial community. Moreover, the magnetic field increased the levels of hdh by 26% and hzs by 35% to promote the nitrogen metabolic process. These results provided novel insights into the magnetic field-enhanced anammox process.

Metabolomics captures the differential metabolites in the replication pathway of snakehead vesiculovirus regulated by glutamine.

Snakehead vesiculovirus (SHVV) is a negative-sense single-stranded RNA virus that infects snakehead fish. This virus leads to illness and mortality, causing significant economic losses in the snakehead aquaculture industry. The replication and spread of SHVV in cells, which requires glutamine as a nitrogen source, is accompanied by alterations in intracellular metabolites. However, the metabolic mechanisms underlying the inhibition of viral replication by glutamine deficiency are poorly understood. This study utilized liquid chromatography-mass spectrometry to measure the differential metabolites between the channel catfish Parasilurus asotus ovary cell line infected with SHVV under glutamine-containing and glutamine-deprived conditions. Results showed that the absence of glutamine regulated 4 distinct metabolic pathways and influenced 9 differential metabolites. The differential metabolites PS(16:0/16:0), 5,10-methylene-THF, and PS(18:0/18:1(9Z)) were involved in amino acid metabolism. In the nuclear metabolism functional pathway, differential metabolites of guanosine were observed. In the carbohydrate metabolism pathway, differential metabolites of UDP-d-galacturonate were detected. In the signal transduction pathway, differential metabolites of SM(d18:1/20:0), SM(d18:1/22:1(13Z)), SM(d18:1/24:1(15 Z)), and sphinganine were found. Among them, PS(18:0/18:1(9Z)), PS(16:0/16:0), and UDP-d-galacturonate were involved in the synthesis of phosphatidylserine and glycoprotein. The compound 5,10-methylene-THF provided raw materials for virus replication, and guanosine and sphingosine are related to virus virulence. The differential metabolites may collectively participate in the replication, packaging, and proliferation of SHVV under glutamine deficiency. This study provides new insights and potential metabolic targets for combating SHVV infection in aquaculture through metabolomics approaches.

Development of 3D printed electrospun vascular graft loaded with tetramethylpyrazine for reducing thrombosis and restraining aneurysmal dilatation.

Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.

Development of 3D Printed Biodegradable, Entirely X-ray Visible Stents for Rabbit Carotid Artery Implantation.

Biodegradable stents are considered a promising strategy for the endovascular treatment of cerebrovascular diseases. The visualization of biodegradable stents is of significance during the implantation and long-term follow-up. Endowing biodegradable stents with X-ray radiopacity can overcome the weakness of intrinsic radioparency of polymers. Hence, this work focuses on the development of an entirely X-ray visible biodegradable stent (PCL-KIO3) composed of polycaprolactone (PCL) and potassium iodate via physical blending and 3D printing. The in vitro results show that the introduction of potassium iodate makes the 3D-printed PCL stents visualizable under X-ray. So far, there is inadequate study about polymeric stent visualization in vivo. Therefore, PCL-KIO3 stents are implanted into the rabbit carotid artery to evaluate the biosafety and visibility performance. During stent deployment, the visualization of the PCL-KIO3 stent effectively helps to understand the position and dilation status of stents. At 6-month follow-up, the PCL-KIO3 stent could still be observed under X-ray and maintains excellent vessel patency. To sum up, this study demonstrates that PCL-KIO3 stent may provide a robust strategy for biodegradable stent visualization.

Kinetic properties of glucose 6-phosphate dehydrogenase and inhibition effects of several metal ions on enzymatic activity in vitro and cells.

Due to the non-degradable and persistent nature of metal ions in the environment, they are released into water bodies, where they accumulate in fish. In order to assess pollution in fish, the enzyme, glucose 6-phosphate dehydrogenase (G6PD), has been employed as a biomarker due to sensitivity to various ions. This study investigates the kinetic properties of the G6PD enzyme in yellow catfish (Pelteobagrus fulvidraco), and analyzes the effects of these metal ions on the G6PD enzyme activity in the ovarian cell line (CCO) of channel catfish (Ictalurus punctatus). IC50 values and inhibition types of G6PD were determined in the metal ions Cu2+, Al3+, Zn2+, and Cd2+. While, the inhibition types of Cu2+ and Al3+ were the competitive inhibition, Zn2+ and Cd2+ were the linear mixed noncompetitive and linear mixed competitive, respectively. In vitro experiments revealed an inverse correlation between G6PD activity and metal ion concentration, mRNA levels and enzyme activity of G6PD increased at the lower metal ion concentration and decreased at the higher concentration. Our findings suggest that metal ions pose a significant threat to G6PD activity even at low concentrations, potentially playing a crucial role in the toxicity mechanism of metal ion pollution. This information contributes to the development of a biomonitoring tool for assessing metal ion contamination in aquatic species.

Anti-inflammatory and anti-oxidative electrospun nanofiber membrane promotes diabetic wound healing via macrophage modulation.

BACKGROUND: In the inflammatory milieu of diabetic chronic wounds, macrophages undergo substantial metabolic reprogramming and play a pivotal role in orchestrating immune responses. Itaconic acid, primarily synthesized by inflammatory macrophages as a byproduct in the tricarboxylic acid cycle, has recently gained increasing attention as an immunomodulator. This study aims to assess the immunomodulatory capacity of an itaconic acid derivative, 4-Octyl itaconate (OI), which was covalently conjugated to electrospun nanofibers and investigated through in vitro studies and a full-thickness wound model of diabetic mice. RESULTS: OI was feasibly conjugated onto chitosan (CS), which was then grafted to electrospun polycaprolactone/gelatin (PG) nanofibers to obtain P/G-CS-OI membranes. The P/G-CS-OI membrane exhibited good mechanical strength, compliance, and biocompatibility. In addition, the sustained OI release endowed the nanofiber membrane with great antioxidative and anti-inflammatory activities as revealed in in vitro and in vivo studies. Specifically, the P/G-CS-OI membrane activated nuclear factor-erythroid-2-related factor 2 (NRF2) by alkylating Kelch-like ECH-associated protein 1 (KEAP1). This antioxidative response modulates macrophage polarization, leading to mitigated inflammatory responses, enhanced angiogenesis, and recovered re-epithelization, finally contributing to improved healing of mouse diabetic wounds. CONCLUSIONS: The P/G-CS-OI nanofiber membrane shows good capacity in macrophage modulation and might be promising for diabetic chronic wound treatment.

Aspirin-Loaded Anti-Inflammatory ZnO-SiO2 Aerogel Scaffolds for Bone Regeneration.

The increasing aging of the population has elevated bone defects to a significant threat to human life and health. Aerogel, a biomimetic material similar to an extracellular matrix (ECM), is considered an effective material for the treatment of bone defects. However, most aerogel scaffolds suffer from immune rejection and poor anti-inflammatory properties and are not well suited for human bone growth. In this study, we used electrospinning to prepare flexible ZnO-SiO2 nanofibers with different zinc concentrations and further assembled them into three-dimensional composite aerogel scaffolds. The prepared scaffolds exhibited an ordered pore structure, and chitosan (CS) was utilized as a cross-linking agent with aspirin (ASA). Interestingly, the 1%ZnO-SiO2/CS@ASA scaffolds not only exhibited good biocompatibility, bioactivity, anti-inflammation, and better mechanical properties but also significantly promoted vascularization and osteoblast differentiation in vitro. In the mouse cranial defect model, the BV/TV data showed a higher osteogenesis rate in the 1%ZnO-SiO2/CS group (10.94 ± 0.68%) and the 1%ZnO-SiO2/CS@ASA group (22.76 ± 1.83%), compared with the control group (5.59 ± 2.08%), and in vivo studies confirmed the ability of 1%ZnO-SiO2/CS@ASA to promote in situ regeneration of new bone. This may be attributed to the fact that Si4+, Zn2+, and ASA released from 1%ZnO-SiO2/CS@ASA scaffolds can promote angiogenesis and bone formation by stimulating the interaction between endothelial cells (ECs) and BMSCs, as well as inducing macrophage differentiation to the M2 type and downregulating the expression of pro-inflammatory factor (TNF-α) to modulate local inflammatory response. These exciting results and evidence suggest that it provides a new and effective strategy for the treatment of bone defects.

The Effect of Distance Education on Self-care in Patients With Heart Failure in the Chronic or Stable Phase: A Systematic Review and Meta-analysis.

BACKGROUND: Health education is important for self-care in patients with heart failure. However, the evidence for the effect of distance education as an intervention to deliver instruction for patients after discharge through digital devices on self-care is limited. OBJECTIVES: In this study, our aim was to explore the effect of distance education on self-care in patients with heart failure. METHODS: We searched 11 electronic databases and 3 trial registries for randomized controlled trials with low risk of bias and high-quality evidence to compare the effect of usual and distance education on self-care. Quality appraisal was performed using the Cochrane Risk of Bias Tool. Using the Review Manager 5.4 tool, a meta-analysis was conducted. Certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Fifteen articles were eligible for this study. Compared with usual education, distance education improved self-care maintenance (mean difference [MD], 6.62; 95% confidence interval [CI], 3.93-9.31; GRADE, moderate quality), self-care management (MD, 5.10; 95% CI, 3.25-6.95; GRADE, high quality), self-care confidence (MD, 6.66; 95% CI, 4.82-8.49; GRADE, high quality), heart failure knowledge (MD, 0.78; 95% CI, 0.01-1.56; GRADE, moderate quality), and quality of life (MD, -5.35; 95% CI, -8.73 to -1.97; GRADE, moderate quality). Subgroup analysis revealed distance education was more effective than usual education in self-care when the intervention was conducted for 1 to 6 months, more than 3 times per month, and a single intervention lasting more than 30 minutes. CONCLUSIONS: This review shows the benefits of distance education on self-care, heart failure knowledge, and quality of life of patients with heart failure. The intervention duration, frequency, and duration of a single intervention could have affected the intervention effect.

An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses.

Marrow niches in osteosarcoma (OS) are a specialized microenvironment that is essential for the maintenance and regulation of OS cells. However, existing animal xenograft models are plagued by variability, complexity, and high cost. Herein, we used a decellularized osteosarcoma extracellular matrix (dOsEM) loaded with extracellular vesicles from human bone marrow-derived stem cells (hBMSC-EVs) and OS cells as a bioink to construct a micro-osteosarcoma (micro-OS) through 3D printing. The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip (OOC) with a built-in recirculating perfusion system. The OOC system successfully integrated bone marrow niches, cell‒cell and cell-matrix crosstalk, and circulation, allowing a more accurate representation of OS characteristics in vivo. Moreover, the OOC system may serve as a valuable research platform for studying OS biological mechanisms compared with traditional xenograft models and is expected to enable precise and rapid evaluation and consequently more effective and comprehensive treatments for OS.

Electrospun membranes chelated by metal magnesium ions enhance pro-angiogenic activity and promote diabetic wound healing.

Diabetic wounds, resulting from skin atrophy due to localized ischemia and hypoxia in diabetic patients, lead to chronic pathological inflammation and delayed healing. Using electrospinning technology, we developed magnesium ion-chelated nanofiber membranes to explore their efficacy in antibacterial, anti-inflammatory, and angiogenic applications for wound healing. These membranes are flexible and elastic, resembling native skin tissue, and possess good hydrophilicity for comfortable wound bed contact. The mechanical properties of nanofiber membranes are enhanced by the chelation of magnesium ions (Mg2+), which also facilitates a long-term slow release of Mg2+. The cytocompatibility of the nanofibrous membranes is influenced by their Mg2+ content: lower levels encourage the proliferation of fibroblasts, endothelial cells, and macrophages, while higher levels are inhibitory. In a diabetic rat model, magnesium ion-chelated nanofibrous membranes effectively reduced early wound inflammation and notably accelerated wound healing. This study highlights the potential of magnesium ion-chelated nanofiber membranes in treating diabetic wounds.

Identification of genes associated with the silk gland size using multi-omics in silkworm (Bombyx mori).

Silk gland size in silkworms (Bombyx mori) affects silk output. However, the molecular mechanisms by which genes regulate silk gland size remain unclear. In this study, silk glands from three pure silkworm strains (A798, A306 and XH) with different silk gland weight phenotypes were compared using transcriptomics and proteomics to identify differentially expressed genes (DEGs) and proteins (DEPs). When comparing A798 to A306 and A798 to XH, 830 and 469 DEGs were up-regulated, respectively. These genes were related to the gene ontology terms, metabolic process, transport activity and biosynthesis process. In addition, 372 and 302 up-regulated differentially expressed proteins were detected in A798 to A306 and A798 to XH, respectively, related to the gene ontology terms, ribosome and protein export, ribosome and polypeptide biosynthesis processes. Moreover, combined transcriptomics, proteomics and weighted correlation network analyses showed that five genes (BGIBMGA002524, BGIBMGA002629, BGIBMGA005659, BGIBMGA005711 and BGIBMGA010889) were significantly associated with the silk gland weight. Reverse Transcription-quantitative real-time Polymerase Chain Reaction (RT-qPCR) and Enzyme linked immunosorbent assay (ELISA) were used to verify the mRNA and protein expression of five genes in the silk glands and tissues of 18 silkworm strains. The results showed that four genes have higher expression levels in heavier silk glands. These genes are associated with glycogen metabolism, fatty acid synthesis and branched chain amino acid metabolism, thus potentially promoting growth and silk protein synthesis. These findings provide valuable insights into the molecular mechanisms underlying the relationship between silk gland weight and silk yield in silkworms.

Relationship between time pressure and consumers' impulsive buying-Role of perceived value and emotions.

Live-streaming e-commerce has become one of the mainstream marketing scenarios, attracting the attention of consumers and the academic community. In live-streaming e-commerce, retailers often use limited-time sales to induce a sense of urgency, prompting consumers to make impromptu purchase decisions. However, existing studies show contradictory results regarding the effectiveness and underlying mechanism of this marketing method. This study empirically investigates the relationship between time pressure and impulsive buying, including affective and cognitive aspects, using the Stimulus-Organism-Response (SOR) and Schachter-Singer (SST) theories. The results suggest that time pressure has a positive relationship with impulsive buying, with an affective rather than cognitive focus. Moreover, the relationship between time pressure and affective (vs. cognitive) impulsive buying is mediated by perceived value. Positive emotions positively moderate, while negative emotions negatively moderate, the relationship between time pressure and affective impulsive buying. This study enhances the understanding of how consumers make purchase decisions under time pressure in live e-commerce scenarios.

[Ecological Risk Assessment and Migration and Accumulation Characteristics of Heavy Metals in Farmland Soil-crop System from Typical Pyrite Mining Area].

To evaluate the ecological risk of heavy metals in the soil-crop system in the superimposed high background and human activities from pyrite mining, the heavy metal contents and chemical speciation in soil and crop samples were analyzed, and these data were used to assess the potential ecological risk and factors affecting the migration ability of heavy metals using bioconcentration factors(BCF), potential ecological risk index(RI), risk assessment code(RAC), and correlation analysis. The results indicate that the average Cd, Cu, Pb, and Zn concentrations exceeded the background values of soils in Zhejiang Province and China. Cd had the greatest potential ecological harm, followed by that of Hg. The bioactive components and potential bioactive components of Cd accounted for 46% and 33%, respectively, indicating relatively high bioavailability. Cu and Pb were mainly in potential bioactive components accounting for 60% and 73%, respectively. The As, Cr, Hg, Ni, and Zn were predominantly residual and accounted for >60%, which indicated low biological activity. The RAC levels were in the following order:Cd>Zn>Cu>Pb>Ni>As>Cr>Hg; soil Cd had the highest ecological risk, mainly with high and extremely high levels, whereas other elements had no risk or low risk. Compared with Cd content in soil, only eight rice samples had Cd contents exceeding the safety limit, and sweet potato samples did not exceed the standard. The migration and enrichment capability of rice in order from strong to weak was s follows:Cd>Zn>Cu>Hg>As>Ni>Cr>Pb; the bioactive component of Cd played a significant role in promoting Cd absorption by rice. Soil OM had a bi-directional effect on Cd bioavailability, whereas soil texture had an indirect effect. This comprehensive study shows that the total amount of heavy metals in soil, chemical speciation, biological activities, absorption, and enrichment of heavy metals by crops should be taken into consideration when assessing the ecological risks in the superimposed areas affected by high background and human activities, such as the pyrite mining area.

Elastic 3D-Printed Nanofibers Composite Scaffold for Bone Tissue Engineering.

Loading nanoparticles into hydrogels has been a conventional approach to augment the printability of ink and the physicochemical characteristics of scaffolds in three-dimensional (3D) printing. However, the efficacy of this enhancement has often proven to be limited. We amalgamate electrospun nanofibers with 3D printing techniques to fabricate a composite scaffold reminiscent of a "reinforced concrete" structure, aimed at addressing bone defects. These supple silica nanofibers are synthesized through a dual-step process involving high-speed homogenization and low-temperature ball milling technology. The nanofibers are homogeneously blended with sodium alginate to create the printing ink. The resultant ink was extruded seamlessly, displaying commendable molding properties, thereby yielding scaffolds with favorable macroscopic morphology. In contrast to nanoparticle-reinforced scaffolds, composite scaffolds containing nanofibers exhibit superior mechanical attributes and bioactivity. These nanofiber composite scaffolds demonstrate enhanced osteoinductive properties in both in vitro and in vivo evaluations. To conclude, this research introduces a novel 3D printing approach where the fabricated nanofiber-infused 3D-printed scaffolds hold the potential to revolutionize the realm of 3D printing in the domain of bone tissue engineering.

Identification of diagnostic markers for ASD: a restrictive interest analysis based on EEG combined with eye tracking.

Electroencephalography (EEG) functional connectivity (EFC) and eye tracking (ET) have been explored as objective screening methods for autism spectrum disorder (ASD), but no study has yet evaluated restricted and repetitive behavior (RRBs) simultaneously to infer early ASD diagnosis. Typically developing (TD) children (n = 27) and ASD (n = 32), age- and sex-matched, were evaluated with EFC and ET simultaneously, using the restricted interest stimulus paradigm. Network-based machine learning prediction (NBS-predict) was used to identify ASD. Correlations between EFC, ET, and Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) were performed. The Area Under the Curve (AUC) of receiver-operating characteristics (ROC) was measured to evaluate the predictive performance. Under high restrictive interest stimuli (HRIS), ASD children have significantly higher α band connectivity and significantly more total fixation time (TFT)/pupil enlargement of ET relative to TD children (p = 0.04299). These biomarkers were not only significantly positively correlated with each other (R = 0.716, p = 8.26e-4), but also with ADOS total scores (R = 0.749, p = 34e-4) and RRBs sub-score (R = 0.770, p = 1.87e-4) for EFC (R = 0.641, p = 0.0148) for TFT. The accuracy of NBS-predict in identifying ASD was 63.4%. ROC curve demonstrated TFT with 91 and 90% sensitivity, and 78.7% and 77.4% specificity for ADOS total and RRB sub-scores, respectively. Simultaneous EFC and ET evaluation in ASD is highly correlated with RRB symptoms measured by ADOS-2. NBS-predict of EFC offered a direct prediction of ASD. The use of both EFC and ET improve early ASD diagnosis.