Decoding the "Fingerprint" of Implant Materials: Insights into the Foreign Body Reaction.

Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.

Rapid Mass Conversion for Environmental Microplastics of Diverse Shapes.

Rivers have been recognized as the primary conveyors of microplastics to the oceans, and seaward transport flux of riverine microplastics is an issue of global attention. However, there is a significant discrepancy in how microplastic concentration is expressed in field occurrence investigations (number concentration) and in mass flux (mass concentration). Of urgent need is to establish efficient conversion models to correlate these two important paradigms. Here, we first established an abundant environmental microplastic dataset and then employed a deep neural residual network (ResNet50) to successfully separate microplastics into fiber, fragment, and pellet shapes with 92.67% accuracy. We also used the circularity (C) parameter to represent the surface shape alteration of pellet-shaped microplastics, which always have a more uneven surface than other shapes. Furthermore, we added thickness information to two-dimensional images, which has been ignored by most prior research because labor-intensive processes were required. Eventually, a set of accurate models for microplastic mass conversion was developed, with absolute estimation errors of 7.1, 3.1, 0.2, and 0.9% for pellet (0.50 ≤ C < 0.75), pellet (0.75 ≤ C ≤ 1.00), fiber, and fragment microplastics, respectively; environmental samples have validated that this set is significantly faster (saves ∼2 h/100 MPs) and less biased (7-fold lower estimation errors) compared to previous empirical models.

Non-negligible Toxicity to Fish in the Early Life Stages Triggered by Aqueous Leachate of Takeaway Plastic Containers.

Ordering takeout is a growing social phenomenon and may raise public health concerns. However, the associated health risk of compounds leaching from plastic packaging is unknown due to the lack of chemical and toxicity data. In this study, 20 chemical candidates were tentatively identified in the environmentally relevant leachate from plastic containers through the nontargeted chemical analysis. Three main components with high responses and/or predicted toxicity were further verified and quantified, namely, 3,5-di-tert-butyl-4-hydroxycinnamic acid (BHC), 2,4-di-tert-butylphenol (2,4-DTBP), and 9-octadecenamide (oleamide). The toxicity to zebrafish larvae of BHC, a degradation product of a widely used antioxidant Irganox 1010, was quite similar to that of the whole plastic leachate. In the same manner, RNA-seq-based ingenuity analysis showed that the affected canonical pathways of zebrafish larvae were quite comparable between BHC and the whole plastic leachate, i.e., highly relevant to neurological disease, metabolic disease, and even behavioral disorder. Longer-term exposure (35 days) did not cause any effect on adult zebrafish but led to decreased hatching rate and obvious neurotoxicity in zebrafish offspring. Collectively, this study strongly suggests that plastic containers can leach out a suite of compounds causing non-negligible impacts on the early stages of fish via direct or parental exposure.

Design, Synthesis, and Anti-Leukemic Evaluation of a Series of Dianilinopyrimidines by Regulating the Ras/Raf/MEK/ERK and STAT3/c-Myc Pathways.

Although the long-term survival rate for leukemia has made significant progress over the years with the development of chemotherapeutics, patients still suffer from relapse, leading to an unsatisfactory outcome. To discover the new effective anti-leukemia compounds, we synthesized a series of dianilinopyrimidines and evaluated the anti-leukemia activities of those compounds by using leukemia cell lines (HEL, Jurkat, and K562). The results showed that the dianilinopyrimidine analog H-120 predominantly displayed the highest cytotoxic potential in HEL cells. It remarkably induced apoptosis of HEL cells by activating the apoptosis-related proteins (cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase (PARP)), increasing apoptosis protein Bad expression, and decreasing the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL). Furthermore, it induced cell cycle arrest in G2/M; concomitantly, we observed the activation of p53 and a reduction in phosphorylated cell division cycle 25C (p-CDC25C) / Cyclin B1 levels in treated cells. Additionally, the mechanism study revealed that H-120 decreased these phosphorylated signal transducers and activators of transcription 3, rat sarcoma, phosphorylated cellular RAF proto-oncogene serine / threonine kinase, phosphorylated mitogen-activated protein kinase kinase, phosphorylated extracellular signal-regulated kinase, and cellular myelocytomatosis oncogene (p-STAT3, Ras, p-C-Raf, p-MEK, p-MRK, and c-Myc) protein levels in HEL cells. Using the cytoplasmic and nuclear proteins isolation assay, we found for the first time that H-120 can inhibit the activation of STAT3 and c-Myc and block STAT3 phosphorylation and dimerization. Moreover, H-120 treatment effectively inhibited the disease progression of erythroleukemia mice by promoting erythroid differentiation into the maturation of erythrocytes and activating the immune cells. Significantly, H-120 also improved liver function in erythroleukemia mice. Therefore, H-120 may be a potential chemotherapeutic drug for leukemia patients.

Case report: Heterozygous variation in the IGHMBP2 gene leading to spinal muscular atrophy with respiratory distress type 1.

A rare autosomal recessive genetic disease is spinal muscular atrophy with respiratory distress type 1 (SMARD 1; OMIM #604320), which is characterized by progressive distal limb muscle weakness, muscular atrophy, and early onset of respiratory failure. Herein, we report the case of a 4-month-old female infant with SMARD type 1 who was admitted to our hospital owing to unexplained distal limb muscle weakness and early respiratory failure. This report summarizes the characteristics of SMARD type 1 caused by heterozygous variation in the immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene by analyzing its clinical manifestations, genetic variation characteristics, and related examinations, aiming to deepen clinicians' understanding of the disease, assisting pediatricians in providing medical information to parents and improving the decision-making process involved in establishing life support.

Microplastics promote methane emission in estuarine and coastal wetlands.

Increasing microplastic (MP) pollution poses significant threats to estuarine and coastal ecosystems. However, the effects of MPs on the emission of methane (CH4), a potent greenhouse gas, within these ecosystems and the underlying regulatory mechanisms have not been elucidated. Here, a combination of 13C stable isotope-based method and molecular techniques was applied to investigate how conventional petroleum-based MPs [polyethylene (PE) and polyvinyl chloride (PVC)] and biodegradable MPs [polylactic acid (PLA) and polyadipate/butylene terephthalate (PBAT)] regulate CH4 production and consumption and thus affect CH4 emission dynamics in estuarine and coastal wetlands. Results indicated that both conventional and biodegradable MPs enhanced the emission of CH4 (P < 0.05), with the promoting effect being more significant for biodegradable MPs. However, the mechanisms by which conventional and biodegradable MPs promote CH4 emissions were different. Specifically, conventional MPs stimulated the emission of CH4 by inhibiting the processes of CH4 consumption, but had no significant effect on CH4 production rate. Nevertheless, biodegradable MPs promoted CH4 emissions via accelerating the activities the methanogens while inhibiting the oxidation of CH4, thus resulting in a higher degree of promoting effect on CH4 emissions than conventional MPs. Consistently, quantitative PCR further revealed a significant increase in the abundance of methyl-coenzyme M reductase gene (mcrA) of methanogens under the exposure of biodegradable MPs (P < 0.05), but not conventional MPs. Furthermore, the relative abundance of most genes involved in CH4 oxidation exhibited varying degrees of reduction after exposure to all types of MPs, based on metagenomics data. This study reveals the effects of MPs on CH4 emissions in estuarine and coastal ecosystems and their underlying mechanisms, highlighting that the emerging biodegradable MPs exhibited a greater impact than conventional MPs on promoting CH4 emissions in these globally important ecosystems, thereby accelerating global climate change.

Microplastic-mediated new mechanism of liver damage: From the perspective of the gut-liver axis.

Microplastics (MPs) are environmental contaminants that are present in all environments and can enter the human body, accumulate in various organs, and cause harm through the ingestion of food, inhalation, and dermal contact. The connection between bowel and liver disease and the interplay between gut, liver, and flora has been conceptualized as the "gut-liver axis". Microplastics can alter the structure of microbial communities in the gut and the liver can also be a target for microplastic invasion. Numerous studies have found that when MPs impair human health, they not only promote dysbiosis of the gut microbiota and disruption of the gut barrier but also cause liver damage. For this reason, the gut-liver axis provides a new perspective in understanding this toxic response. The cross-talk between MPs and the gut-liver axis has attracted the attention of the scientific community, but knowledge about whether MPs cause gut-liver interactions through the gut-liver axis is still very limited, and the effect of MPs on liver injury is not well understood. MPs can directly induce microbiota disorders and gut barrier dysfunction. As a result, harmful bacteria and metabolites in the gut enter the blood through the weak intestinal barrier (portal vein channel along the gut-liver axis) and reach the liver, causing liver damage (inflammatory damage, metabolic disorders, oxidative stress, etc.). This review provides an integrated perspective of the gut-liver axis to help conceptualize the mechanisms by which MP exposure induces gut microbiota dysbiosis and hepatic injury and highlights the connection between MPs and the gut-liver axis. Therefore, from the perspective of the gut-liver axis, targeting intestinal flora is an important way to eliminate microplastic liver damage.

Differences of microplastics and nanoplastics in urban waters: Environmental behaviors, hazards, and removal.

Microplastics (MPs) and nanoplastics (NPs) are ubiquitous in the aquatic environment and have caused widespread concerns globally due to their potential hazards to humans. Especially, NPs have smaller sizes and higher penetrability, and therefore can penetrate the human barrier more easily and may pose potentially higher risks than MPs. Currently, most reviews have overlooked the differences between MPs and NPs and conflated them in the discussions. This review compared the differences in physicochemical properties and environmental behaviors of MPs and NPs. Commonly used techniques for removing MPs and NPs currently employed by wastewater treatment plants and drinking water treatment plants were summarized, and their weaknesses were analyzed. We further comprehensively reviewed the latest technological advances (e.g., emerging coagulants, new filters, novel membrane materials, photocatalysis, Fenton, ozone, and persulfate oxidation) for the separation and degradation of MPs and NPs. Microplastics are more easily removed than NPs through separation processes, while NPs are more easily degraded than MPs through advanced oxidation processes. The operational parameters, efficiency, and potential governing mechanisms of various technologies as well as their advantages and disadvantages were also analyzed in detail. Appropriate technology should be selected based on environmental conditions and plastic size and type. Finally, current challenges and prospects in the detection, toxicity assessment, and removal of MPs and NPs were proposed. This review intends to clarify the differences between MPs and NPs and provide guidance for removing MPs and NPs from urban water systems.

Leaching potentials of microplastic fibers and UV stabilizers from coastal-littered face masks.

Synthetic fibrous textiles are ubiquitous plastic commodities in everyday existence. Nevertheless, there exists a dearth of understanding regarding their environmental occurrence and the releasing capacities of associated additives. In this study, ten additives were determined in twenty-eight kinds of daily used plastic products including face masks, synthetic clothing, and food containers. Our results revealed that a typical kind of fibrous plastic, face masks, contained a greater variety of additives with UV stabilizers in particular, when compared to other plastic commodities. The above phenomena triggered our field investigation for the occurrence and release potentials of face mask fibers and the co-existing UV stabilizers into the environment. We further collected 114 disposed masks from coastal areas and analyzed their UV stabilizer concentrations. Results showed that the abundance of littered face masks ranged from 40-1846 items/km2 along the Yangtze Estuary, China; and UV stabilizers were of 0.3 ± 0.7 ng/g and 0.7 ± 1.7 ng/g in main bodies and ear ropes, respectively. The UV stabilizer concentrations in the field collected masks were only ∼7 % of their new counterparts, implying their potential leaching after disposal. By simulating the weathering scenario, we predict that a substantial amount of microplastics, with 1.1 × 1010 polypropylene fibers and 3.7 × 1010 polyester fibers, are probably be released daily into the coastal environment after face masks disposal; whereas the accompanied leaching amount of UV stabilizers was relatively modest under the current scenario.

Dissolution-precipitation method concatenated sodium alginate/MOF-derived magnetic multistage pore carbon magnetic solid phase extraction for determination of antioxidants and ultraviolet stabilizers in polylactic acid food contact plastics.

Antioxidants and UV stabilizers have some endocrine disrupting effects and liver toxicity. Both types of additives are still widely used in food contact plastics to improve the durability of plastic products. However, efficient and rapid detection of antioxidants and UV stabilizers has been a challenge due to the complexity of the plastic matrix and the low content of antioxidants and UV stabilizers. In this study, a sodium alginate/MOF-derived magnetic multistage pore carbon material (MIL-101(Fe)/SA-CAs) was developed, having the merits of abundant multistage pore structure, large specific surface area, and good magnetic separation properties. Thus, this material was selected as the sorbent for magnetic solid-phase extraction combined with a dissolution-precipitation method for the extraction and purification of antioxidants and UV stabilizers from polylactic acid food contact plastics. The extraction parameters such as sorbent type, sorbent dosage, sample solution pH, ionic strength, sorption time, elution solution type, volume, and time were investigated. Under the optimized conditions, all the analytes determined by UPLC-MS/MS showed good linear range (r > 0.99), detection limit (0.023-3.105 ng g-1), accuracy (70.6-102.3 %), and reproducibility (RSD<9.8 %). Further, the developed method was applied to determine the antioxidants and UV stabilizers in polylactic acid lunch boxes and straws, showing excellent applicability. The results showed that the antioxidants and UV stabilizers were detected in some of the samples, with a maximum detection of antioxidant 1010 at 7297 ng g-1. This study provided a sensitive, efficient, and environmentally friendly method for antioxidants and UV stabilizers in polylactic acid food contact plastics. The ideas for the design of environmentally friendly metal-organic frameworks and biomass composite multifunctional materials would promise in the sample pretreatment field for the emerging contaminants.

Depression and the Risk of Dementia and All-Cause Mortality Among Japanese Older Adults: A 9-Year Longitudinal Study From JAGES.

BACKGROUND: This study aims to investigate the association and dose-response relationship between depression, dementia, and all-cause mortality based on a national cohort study of older adults in Japan. METHODS: We conducted a longitudinal study of 44,546 participants ≥65 years from 2010-2019 Japanese Gerontological Evaluation Study. The Geriatric Depression Scale-15 was used to assess depressive symptoms and the long-term care insurance was used to assess dementia. Fine-Gray models and Cox proportional hazard models were used to explore the effect of depression severity on the incidence of dementia and all-cause mortality, respectively. Causal mediation analysis were used to explore the extent of association between dementia-mediated depression and all-cause mortality. RESULTS: We found that both minor and major depressive symptoms were associated with the increased cumulative incidence of dementia and all-cause mortality, especially major depressive symptoms (p < .001). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were 1.25 (1.19-1.32) for minor depressive symptoms and 1.42 (1.30-1.54) for major depressive symptoms in comparison to non-depression; p for trend < .001. The multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.21-1.33) for minor depressive symptoms and 1.51 (1.41-1.62) for major depressive symptoms in comparison to non-depression; p for trend < .001. Depression has a stronger impact on dementia and all-cause mortality among the younger group. In addition, dementia significantly mediated the association between depression and all-cause mortality. DISCUSSION: Interventions targeting major depression may be an effective strategy for preventing dementia and premature death.

Simultaneous detection of norepinephrine and 5-hydroxytryptophan using poly-alizarin/multi-walled carbon nanotubes-graphene modified carbon fiber microelectrode array sensor.

Multi-walled carbon nanotubes, graphene and alizarin polymer composites coated carbon fiber microelectrode array sensor (p-AZ/MWCNT-GR/CFMEA) was constructed and used for the simultaneous detection of norepinephrine (NE) and 5-hydroxytryptophan (5-HT). The morphology and structural characteristics of sensor are characterized using scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Its electrochemical behavior has been studied with cyclic voltammetry and electrochemical impedance spectroscopy. The sensor exhibits excellent electrochemical activity for the oxidation of NE and 5-HT, two well separated oxidation peaks with the peak potential difference of 220 mV are observed on the cyclic voltammogram. NE and 5-HT both show two electrons and two protons electrochemical reaction on the p-AZ/MWCNT-GR/CFMEA. Under the optimized experiment conditions, the linear ranges of the sensor for NE and 5-HT are 0. 08- 8 µM and 0. 1-20 µM with detection limits of 4. 22 nM and 14. 2 nM (S/N = 3), respectively. In addition, the microsensor array show good reproducibility, stability and selectivity for the determination of NE and 5-HT. Finally, the p-AZ/MWCNT-GR/CFMEA is applied to the simultaneous detection of NE and 5-HT in human serum samples and macrophages.