S1-END-seq reveals DNA secondary structures in human cells.

DNA becomes single stranded (ssDNA) during replication, transcription, and repair. Transiently formed ssDNA segments can adopt alternative conformations, including cruciforms, triplexes, and quadruplexes. To determine whether there are stable regions of ssDNA in the human genome, we utilized S1-END-seq to convert ssDNA regions to DNA double-strand breaks, which were then processed for high-throughput sequencing. This approach revealed two predominant non-B DNA structures: cruciform DNA formed by expanded (TA)n repeats that accumulate in microsatellite unstable human cancer cell lines and DNA triplexes (H-DNA) formed by homopurine/homopyrimidine mirror repeats common across a variety of cell lines. We show that H-DNA is enriched during replication, that its genomic location is highly conserved, and that H-DNA formed by (GAA)n repeats can be disrupted by treatment with a (GAA)n-binding polyamide. Finally, we show that triplex-forming repeats are hotspots for mutagenesis. Our results identify dynamic DNA secondary structures in vivo that contribute to elevated genome instability.

Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.

Prelamin A is a farnesylated precursor of lamin A, a nuclear lamina protein. Accumulation of the farnesylated prelamin A variant progerin, with an internal deletion including its processing site, causes Hutchinson-Gilford progeria syndrome. Loss-of-function mutations in ZMPSTE24, which encodes the prelamin A processing enzyme, lead to accumulation of full-length farnesylated prelamin A and cause related progeroid disorders. Some data suggest that prelamin A also accumulates with physiological aging. Zmpste24-/- mice die young, at ∼20 wk. Because ZMPSTE24 has functions in addition to prelamin A processing, we generated a mouse model to examine effects solely due to the presence of permanently farnesylated prelamin A. These mice have an L648R amino acid substitution in prelamin A that blocks ZMPSTE24-catalyzed processing to lamin A. The LmnaL648R/L648R mice express only prelamin and no mature protein. Notably, nearly all survive to 65 to 70 wk, with ∼40% of male and 75% of female LmnaL648R/L648R mice having near-normal lifespans of 90 wk (almost 2 y). Starting at ∼10 wk of age, LmnaL648R/L648R mice of both sexes have lower body masses than controls. By ∼20 to 30 wk of age, they exhibit detectable cranial, mandibular, and dental defects similar to those observed in Zmpste24-/- mice and have decreased vertebral bone density compared to age- and sex-matched controls. Cultured embryonic fibroblasts from LmnaL648R/L648R mice have aberrant nuclear morphology that is reversible by treatment with a protein farnesyltransferase inhibitor. These novel mice provide a model to study the effects of farnesylated prelamin A during physiological aging.

Untargeted Metabolomics Analysis of Gingival Tissue in Patients with Severe Periodontitis.

The purpose of this study was to determine potential metabolic biomarkers and therapeutic drugs in the gingival tissue of individuals with periodontitis. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the gingival tissue samples from 20 patients with severe periodontitis and 20 healthy controls. Differential metabolites were identified using variable important in projection (VIP) values from the orthogonal partial least squares discrimination analysis (OPLS-DA) model and then verified for significance between groups using a two-tailed Student's t test. In total, 65 metabolites were enriched in 33 metabolic pathways, with 40 showing a significant increase and 25 expressing a significant decrease. In addition, it was found that patients with severe periodontitis have abnormalities in metabolic pathways, such as glucose metabolism, purine metabolism, amino acid metabolism, and so on. Furthermore, based on a multidimensional analysis, 12 different metabolites may be the potential biomarkers of severe periodontitis. The experiment's raw data have been uploaded to the MetaboLights database, and the project number is MTBLS8357. Moreover, osteogenesis differentiation characteristics were detected in the selected metabolites. The findings may provide a basis for the study of diagnostic biomarkers and therapeutic metabolites in severe periodontitis.

Generation and Fate of Nanoplastics in the Intestine of Plastic-Degrading Insect (Tenebrio molitor Larvae) during Polystyrene Microplastic Biodegradation.

The insect Tenebrio molitor exhibits ultrafast efficiency in biodegrading polystyrene (PS). However, the generation and fate of nanoplastics (NPs) in the intestine during plastic biodegradation remain unknown. In this study, we investigated the biodegradation of PS microplastics (MPs) mediated by T. molitor larvae over a 4-week period and confirmed biodegradation by analyzing Δδ13C in the PS before and after biotreatment (-28.37‰ versus -24.88‰) as an effective tool. The ·OH radicals, primarily contributed by gut microbiota, and H2O2, primarily produced by the host, both increased after MP digestion. The size distribution of residual MP particles in excrements fluctuated within the micrometer ranges. PS NPs were detected in the intestine but not in the excrements. At the end of Weeks 1, 2, 3, and 4, the concentrations of PS NPs in gut tissues were 3.778, 2.505, 2.087, and 2.853 ng/lava, respectively, while PS NPs in glands were quantified at 0.636, 0.284, and 0.113 ng/lava and eventually fell below the detection limit. The PS NPs in glands remained below the detection limit at the end of Weeks 5 and 6. This indicates that initially, NPs generated in the gut entered glands, then declined gradually and eventually disappeared or possibly biodegraded after Week 4, associated with the elevated plastic-degrading capacities of T. molitor larvae. Our findings unveil rapid synergistic MP biodegradation by the larval host and gut microbiota, as well as the fate of generated NPs, providing new insights into the risks and fate associated with NPs during invertebrate-mediated plastic biodegradation.

Understanding the Ecological Robustness and Adaptability of the Gut Microbiome in Plastic-Degrading Superworms (Zophobas atratus) in Response to Microplastics and Antibiotics.

Recent discoveries indicate that several insect larvae are capable of ingesting and biodegrading plastics rapidly and symbiotically, but the ecological adaptability of the larval gut microbiome to microplastics (MPs) remains unclear. Here, we described the gut microbiome assemblage and MP biodegradation of superworms (Zophobas atratus larvae) fed MPs of five major petroleum-based polymers (polyethylene, polypropylene, polystyrene, polyvinyl chloride, and polyethylene terephthalate) and antibiotics. The shift of molecular weight distribution, characteristic peaks of C═O, and metabolic intermediates of residual polymers in egested frass proved depolymerization and biodegradation of all MPs tested in the larval intestines, even under antibiotic suppression. Superworms showed a wide adaptation to the digestion of the five polymer MPs. Antibiotic suppression negatively influenced the survival rate and plastic depolymerization patterns. The larval gut microbiomes differed from those fed MPs and antibiotics, indicating that antibiotic supplementation substantially shaped the gut microbiome composition. The larval gut microbiomes fed MPs had higher network complexity and stability than those fed MPs and antibiotics, suggesting that the ecological robustness of the gut microbiomes ensured the functional adaptability of larvae to different MPs. In addition, Mantel's test indicated that the gut microbiome assemblage was obviously related to the polymer type, the plastic degradability, antibiotic stress, and larval survival rate. This finding provided novel insights into the self-adaptation of the gut microbiome of superworms in response to different MPs.

Exposure Pathways and Toxicity of Microplastics in Terrestrial Insects.

The detrimental effects of plastics on aquatic organisms, including those of macroplastics, microplastics, and nanoplastics, have been well established. However, knowledge on the interaction between plastics and terrestrial insects is limited. To develop effective strategies for mitigating the impact of plastic pollution on terrestrial ecosystems, it is necessary to understand the toxicity effects and influencing factors of plastic ingestion by insects. An overview of current knowledge regarding plastic ingestion by terrestrial insects is provided in this Review, and the factors influencing this interaction are identified. The pathways through which insects interact with plastics, which can lead to plastic accumulation and microplastic transfer to higher trophic levels, are also discussed using an overview and a conceptual model. The diverse impacts of plastic exposure on insects are discussed, and the challenges in existing studies, such as a limited focus on certain plastic types, are identified. Further research on standardized methods for sampling and analysis is crucial for reliable research, and long-term monitoring is essential to assess plastic trends and ecological impacts in terrestrial ecosystems. The mechanisms underlying these effects need to be uncovered, and their potential long-term consequences for insect populations and ecosystems require evaluation.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA.

Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs.

Phthalate exposure aggravates periodontitis by activating NFκB pathway.

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.

The accuracy and reliability of different midsagittal planes in the symmetry assessment using cone-beam computed tomography.

Symmetry is an essential component of esthetic assessment. Accurate assessment of facial symmetry is critical to the treatment plan of orthognathic surgery and orthodontic treatment. However, there is no internationally accepted midsagittal plane (MSP) for orthodontists and orthognathic surgeons. The purpose of this study was to explore a clinically friendly MSP, which is more accurate and reliable than what is commonly used in symmetry assessment. Forty patients with symmetric craniofacial structures were analyzed on cone-beam computed tomography (CBCT) scans. The CBCT data were exported to the Simplant Pro software to build four reference planes that were constructed by nasion (N), basion (Ba), sella (S), odontoid (Dent), or incisive foramen (IF). A total of 31 landmarks were located to determine which reference plane is the most optimal MSP by comparing the asymmetry index (AI). The mean value of AI showed a significant difference (p < 0.05) among four reference planes. Also, the mean value of AI for all landmarks showed that Plane 2 (consisting of N, Ba, and IF) and Plane 4 (consisting of N, IF, and Dent) were more accurate and stable. In conclusion, the MSP consisting of N, Dent, and IF shows more accuracy and reliability than the other planes. Further, it is more clinically friendly because of its significant advantage in landmarking.

AdNAC20 Regulates Lignin and Coumarin Biosynthesis in the Roots of Angelica dahurica var. Formosana.

Angelica dahurica var. formosana (ADF), which belongs to the Umbelliferae family, is one of the original plants of herbal raw material Angelicae Dahuricae Radix. ADF roots represent an enormous biomass resource convertible for disease treatment and bioproducts. But, early bolting of ADF resulted in lignification and a decrease in the coumarin content in the root, and roots lignification restricts its coumarin for commercial utility. Although there have been attempts to regulate the synthesis ratio of lignin and coumarin through biotechnology to increase the coumarin content in ADF and further enhance its commercial value, optimizing the biosynthesis of lignin and coumarin remains challenging. Based on gene expression analysis and phylogenetic tree profiling, AdNAC20 as the target for genetic engineering of lignin and coumarin biosynthesis in ADF was selected in this study. Early-bolting ADF had significantly greater degrees of root lignification and lower coumarin contents than that of the normal plants. In this study, overexpression of AdNAC20 gene plants were created using transgenic technology, while independent homozygous transgenic lines with precise site mutation of AdNAC20 were created using CRISPR/Cas9 technology. The overexpressing transgenic ADF plants showed a 9.28% decrease in total coumarin content and a significant 12.28% increase in lignin content, while knockout mutant plants showed a 16.3% increase in total coumarin content and a 33.48% decrease in lignin content. Furthermore, 29,671 differentially expressed genes (DEGs) were obtained by comparative transcriptomics of OE-NAC20, KO-NAC20, and WT of ADF. A schematic diagram of the gene network interacting with AdNAC20 during the early-bolting process of ADF was constructed by DEG analysis. AdNAC20 was predicted to directly regulate the transcription of several genes with SNBE-like motifs in their promoter, such as MYB46, C3H, and CCoAOMT. In this study, AdNAC20 was shown to play a dual pathway function that positively enhanced lignin formation but negatively controlled coumarin formation. And the heterologous expression of the AdNAC20 gene at Arabidopsis thaliana proved that the AdNAC20 gene also plays an important role in the process of bolting and flowering.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Recent Advances in Tailored Fabrication and Properties of Biobased Self-Healing Polyurethane.

With the emergence of challenges in the environmental degradation and resource scarcity fields, the research of biobased self-healing polyurethane (BSPU) has become a prevailing trend in the technology of the polyurethane industry and a promising direction for developing biomass resources. Here, the production of BSPU from lignocellulose, vegetable oil, chitosan, collagen, and coumarin is classified, and the principles of designing polyurethane based on compelling examples using the latest methods and current research are summarized. Moreover, the impact of biomass materials on self-healing and mechanical properties, as well as the tailored performance method, are presented in detail. Finally, the applications of BSPU in biomedicine, sensors, coatings, etc. are also summarized, and the possible challenges and development prospects are explored to helpfully make progress in the development of BSPU. These findings demonstrate valuable references and practical significance for future BSPU research.

Unveiling Fragmentation of Plastic Particles during Biodegradation of Polystyrene and Polyethylene Foams in Mealworms: Highly Sensitive Detection and Digestive Modeling Prediction.

It remains unknown whether plastic-biodegrading macroinvertebrates generate microplastics (MPs) and nanoplastics (NPs) during the biodegradation of plastics. In this study, we utilized highly sensitive particle analyzers and pyrolyzer-gas chromatography mass spectrometry (Py-GCMS) to investigate the possibility of generating MPs and NPs in frass during the biodegradation of polystyrene (PS) and low-density polyethylene (LDPE) foams by mealworms (Tenebrio molitor larvae). We also developed a digestive biofragmentation model to predict and unveil the fragmentation process of ingested plastics. The mealworms removed 77.3% of ingested PS and 71.1% of ingested PE over a 6-week test period. Biodegradation of both polymers was verified by the increase in the δ13C signature of residual plastics, changes in molecular weights, and the formation of new oxidative functional groups. MPs accumulated in the frass due to biofragmentation, with residual PS and PE exhibiting the maximum percentage by number at 2.75 and 7.27 µm, respectively. Nevertheless, NPs were not detected using a laser light scattering sizer with a detection limit of 10 nm and Py-GCMS analysis. The digestive biofragmentation model predicted that the ingested PS and PE were progressively size-reduced and rapidly biodegraded, indicating the shorter half-life the smaller plastic particles have. This study allayed concerns regarding the accumulation of NPs by plastic-degrading mealworms and provided critical insights into the factors controlling MP and NP generation during macroinvertebrate-mediated plastic biodegradation.

Gut Microbiome Associating with Carbon and Nitrogen Metabolism during Biodegradation of Polyethene in Tenebrio larvae with Crop Residues as Co-Diets.

Tenebrio molitor and Tenebrio obscurus (Coleoptera: Tenebrionidae) larvae are two commercial insects that eat plant and crop residues as diets and also biodegrade synthetic plastics polyethylene (PE). We examined biodegradation of low-density PE (LDPE) foam (Mn = 28.9 kDa and Mw = 342.0 kDa) with and without respective co-diets, i.e., wheat brain (WB) or corn flour (CF), corn straw (CS), and rice straw (RS) at 4:1 (w/w), and their gut microbiome and genetic metabolic functional groups at 27.0 ± 0.5 °C after 28 days of incubation. The presence of co-diets enhanced LDPE consumption in both larvae and broad-depolymerized the ingested LDPE. The diet type shaped gut microbial diversity, potential pathways, and metabolic functions. The sequence of effectiveness of co-diets was WB or CF > CS > RS for larval development and LDPE degradation. Co-occurrence networks indicated that the larvae co-fed with LDPE displayed more complex correlations of gut microbiome than the larvae fed with single diets. The primary diet of WB or CF and crop residues CS and RS provided energy and nitrogen source to significantly enhance LDPE biodegradation with synergistic activities of the gut microbiota. For the larvae fed LDPE and LDPE plus co-diets, nitrogen fixation function was stimulated compared to normal diets and associated with LDPE biodegradation.

Nanogels with covalently bound and releasable trehalose for autophagy stimulation in atherosclerosis.

Atherosclerosis, cholesterol-driven plaque formation in arteries, is a complex multicellular disease which is a leading cause of vascular diseases. During the progression of atherosclerosis, the autophagic function is impaired, resulting in lipid accumulation-mediated foam cell formation. The stimulation of autophagy is crucial for the recovery of cellular recycling process. One of the potential autophagy inducers is trehalose, a naturally occurring non-reducing disaccharide. However, trehalose has poor bioavailability due to its hydrophilic nature which results in poor penetration through cell membranes. To enhance its bioavailability, we developed trehalose-releasing nanogels (TNG) for the treatment of atherosclerosis. The nanogels were fabricated through copolymerization of 6-O-acryloyl-trehalose with the selected acrylamide-type monomers affording a high trehalose conjugation (~ 58%, w/w). TNG showed a relatively small hydrodynamic diameter (dH, 67 nm) and a uniform spherical shape and were characterized by negative ζ potential (-18 mV). Thanks to the trehalose-rich content, TNG demonstrated excellent colloidal stability in biological media containing serum and were non-hemolytic to red blood cells. In vitro study confirmed that TNG could stimulate autophagy in foam cells and enhance lipid efflux and in vivo study in ApoE-/- mice indicated a significant reduction in atherosclerotic plaques, while increasing autophagic markers. In conclusion, TNG hold great promise as a trehalose delivery system to restore impaired autophagy-mediated lipid efflux in atherosclerosis and subsequently reduce atherosclerotic plaques.

A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.

Biodegradation of polyvinyl chloride, polystyrene, and polylactic acid microplastics in Tenebrio molitor larvae: Physiological responses.

It is widely understood that microplastics (MPs) can induce various biological stresses in macroinvertebrates that are incapable of biodegrading plastics. However, the biodegradation and physiological responses of plastic-degrading macroinvertebrates toward MPs of different degradability levels remain unexplored. In this study, Tenebrio molitor larvae (mealworms) were selected as a model of plastics-degrading macroinvertebrate, and were tested against three common plastics of different degradability rankings: polyvinyl chloride (PVC), polystyrene (PS), and polylactic acid (PLA) MPs (size <300 µm). These three MPs were biodegraded with the rate sequence of PLA > PS > PVC, resulting in a reversed order of negative physiological responses (body weight loss, decreased survival, and biomass depletion) of mealworms. Simultaneously, the levels of reactive oxygen species (ROS), antioxidant enzyme activities, and lipid peroxidation were uniformly increased as polymer degradability decreased and intermediate toxicity increased. PVC MPs exhibited higher toxicity than the other two polymers. The oxidative stresses were effectively alleviated by supplementing co-diet bran. The T. molitor larvae fed with PLA plus bran showed sustainable growth without an increase in oxidative stress. The results provide new insights into the biotoxicity of MPs on macroinvertebrates and offer comprehensive information on the physiological stress responses of plastic-degrading macroinvertebrates during the biodegradation of plastics with different degradability levels.

Construction of Core-Shell NanoMOFs@microgel for Aqueous Lubrication and Thermal-Responsive Drug Release.

The construction of porous nanocarriers with good lubricating performance and stimuli-responsive drug release is significant for the synergetic therapy of osteoarthritis (OA). Although metal-organic framework nanoparticles (nanoMOFs) as carriers can support drug delivery, achieving the synergy of aqueous lubrication and stimuli-responsive drug release is challenging. In this work, a core-shell nanoMOFs@poly(N-isopropylacrylamide) (PNIPAm) microgel hybrid via one-pot soap-free emulsion polymerization is developed. Programmable growth of the PNIPAm microgel layer on the surface of nanoMOFs is achieved by tuning the concentration of the monomer and the crosslinker in the reaction. Reversible swelling-collapsing behaviors of the hybrid are realized by tuning the temperature below and above the lower critical solution temperature. When used as water lubrication additives, the hybrid enables reductions in both the coefficient of friction and wear volume. In vitro thermal-responsive drug release is demonstrated on the diclofenac sodium-loaded hybrid by controlling the swelling and collapsing states of the PNIPAm nanolayer. Moreover, the good biocompatibility of the hybrid is verified by culturing toward HeLa and BEAS-2B cells. These results establish a nanoMOFs@microgel hybrid that can achieve friction and wear reduction and thermal-responsive drug release.