Redox potential ultrasensitive nanoparticle for the targeted delivery of camptothecin to HER2-positive cancer cells.

Ideal "smart" nanoparticles for drug delivery should enhance therapeutic efficacy without introducing side effects. To achieve that, we developed a drug delivery system (HCN) based on a polymer-drug conjugate of poly[2-(pyridin-2-yldisulfanyl)]-graft-poly(ethylene glycol) and camptothecin with an intracellularly cleavable linker and human epidermal growth factor receptor 2 (HER2) targeting ligands. An in vitro drug release study found that HCN was stable in the physiological environment and supersensitive to the stimulus of elevated intracellular redox potential, releasing all payloads in less than 30 min. Furthermore, confocal microscopy revealed that HCN could specifically enter HER2-positive cancer cells. As a consequence, HCN could effectively kill HER2-positive cancer cells while not affecting HER2-negative cells.

Accelerated hazards model based on parametric families generalized with Bernstein polynomials.

A transformed Bernstein polynomial that is centered at standard parametric families, such as Weibull or log-logistic, is proposed for use in the accelerated hazards model. This class provides a convenient way towards creating a Bayesian nonparametric prior for smooth densities, blending the merits of parametric and nonparametric methods, that is amenable to standard estimation approaches. For example optimization methods in SAS or R can yield the posterior mode and asymptotic covariance matrix. This novel nonparametric prior is employed in the accelerated hazards model, which is further generalized to time-dependent covariates. The proposed approach fares considerably better than previous approaches in simulations; data on the effectiveness of biodegradable carmustine polymers on recurrent brain malignant gliomas is investigated.

Effects of combined modification of sulfonation, oxygen plasma and silane on the bond strength of PEEK to resin.

OBJECTIVE: This study aimed to evaluate the combined effects of sulfonation, non-thermal oxygen plasma and silane on the shear bond strength (SBS) of PEEK to resin materials. MATERIALS AND METHODS: Two hundred and eighty specimens were randomly divided into four groups: (A) untreated; (B) sulfonation for 60 s; (C) oxygen plasma for 20 min; (D) sulfonation for 60 s and oxygen plasma for 20 min. According to the instructions, 120 samples (N = 30) were coated with silane, adhesive, and resin composites. Each group of bonding specimens was divided into two subgroups (n = 15) to measure immediate and post-aging SBS. The surface morphology and the interface between the samples and adhesive were analyzed through SEM. Physicochemical characteristics of the surface and mechanical properties were determined through XPS, FTIR, light interferometry, contact angle measurement, and three-point bending tests. RESULTS: Sulfonation produced a porous layer of approximately 20 µm thickness on the surface, and the oxygen plasma increased the O/C ratio and oxygen-containing groups of the sample surface. After coating with silane, the SBS values of sulfonated PEEK and plasma-treated PEEK increased (9.96 and 10.72 MPa, respectively), and dual-modified PEEK exhibited the highest SBS value (20.99 MPa), which was significantly higher than that of blank group (p > 0.01). After 10,000 thermal cycles, the dual-modified PEEK still displayed a favorable SBS (18.68 MPa). SIGNIFICANCE: Sulfonation strengthened the mechanical interlocking between PEEK and the resin while oxygen plasma established a chemical bonding between silane and PEEK. This dual modification of the surface microstructure and chemical state synergistically improved the bond strength of PEEK to resin and resulted in considerable long-term effects.

Association between clusters of antibodies against periodontal microorganisms and Alzheimer disease mortality: Evidence from a nationally representative survey in the USA.

BACKGROUND: Alzheimer disease (AD) has been linked with periodontal microorganisms such as Porphyromonas gingivalis in observational and mechanistic studies. IgG antibodies against periodontal microorganisms which are markers of past and current periodontal infection have been correlated with cognitive impairment. We examined associations between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and AD mortality. METHODS: Individuals participating in the Third National Health and Nutrition Examination Survey (NHANES III) with complete data on IgG titers were followed up between 1988 and December 31, 2019. The outcome was AD mortality, and the main exposures were IgG antibodies against periodontal microorganisms classified into four mutually exclusive groups using cluster analysis. Survey-weighted Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the relationship between clusters and AD mortality. RESULTS: With up to 21 years of follow-up, 160 AD-related deaths were documented. In the multivariable-adjusted model, AD mortality overall was not associated with the Red-Green (aHR 1.18; 95% CI, 0.46-3.07), Yellow-Orange (aHR 1.36; 95% CI, 0.58-3.19), Orange-Blue (aHR 0.63; 95%, CI, 0.33-1.21), and the Orange-Red (aHR 0.79; 95% CI, 0.37-1.70) when the upper tertiles were compared to the bottom tertiles. However, the subgroup of middle-aged individuals in the highest tertile of the Red-Green cluster, but not older individuals, had a 13% higher risk of AD mortality (aHR 1.13; 95% CI, 1.02-1.26) compared with those in the bottom tertile. CONCLUSION: Clusters of IgG antibodies against periodontal microorganisms did not predict AD mortality in this study.

Effects of polyurethane microplastics combined with cadmium on maize growth and cadmium accumulation under different long-term fertilisation histories.

Agricultural production uses different types of fertilisation treatments, typically employing the combined application of organic fertiliser (OF) or organic-inorganic fertiliser (OIF) to improve soil quality. When coupled with cadmium (Cd), microplastics (MPs) affect plant growth and Cd accumulation in soils treated with different fertilisers. This study systematically examined the effects of polyurethane (PU) MPs coupled with Cd on the growth characteristics, root metabolite characteristics, rhizosphere bacterial community structure, and Cd bioavailability of maize under different long-term fertilisation treatments and soil types (red/cinnamon soil). The combined effects of PU MPs and Cd on maize growth differed across fertilisation treatments. Under OF, maize plants accumulated more Cd than under OIF. The accumulation of Cd in maize plants in red soil was twice that in cinnamon soil. Under OF, PU MPs promoted Cd activation by decreasing the soil pH, while root metabolites promoted Cd adsorption sites by synthesising specific amino acids, degrading aromatic compounds, and synthesising pantothenic acid and coenzyme A. Under OF, PU MPs can lower the soil pH to promote the activation of cadmium, while root metabolites promote root growth and increase cadmium adsorption sites by synthesizing specific amino acids, degrading aromatic compounds, and synthesizing pantothenic acid and coenzyme A, hereby promoting root Cd absorption. Under OIF, PU MPs act by influencing the biosynthesis of amino acids in root metabolites, enriching energy metabolism pathways, promoting the transport and translocation of mineral nutrients, thereby amplifying the "toxic effects" of Cd. This study provides new insights into the risk assessment of PU MPs and Cd coupling under different fertilisation treatments, and suggests that the prevention and control of combined PU MPs and Cd pollution in red soil under OF treatment should receive more attention in the future.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Urban pipeline rainwater runoff is an important pathway for land-based microplastics transport to inland surface water: A case study in Beijing.

Microplastics (MPs) as new environmental pollutants are receiving increasing attention worldwide. Urban rainwater runoff plays an important role in facilitating the migration of land-based MPs to surface water. Previous research has focused predominantly on aquatic ecosystems, whereas research on this migration pathway and the characteristics of MPs in rainwater pipelines draining from different land-use types is still lacking. This study investigated the abundance and characteristics of MPs in rainfall and pipeline rainwater runoff from main roads, office complexes, an agricultural experiment station, and residential areas during different rainfall periods in Haidian District, Beijing, China. Microplastic abundance in pipeline rainwater runoff ranged from 1.6 to 29.6 items L-1, of which 0.7 to 6.0 items L-1 were derived from rainfalls, accounting for 24.0 % to 77.4 % of the total. Microplastic abundances in rainfall and pipeline rainwater runoff decreased significantly as rainfall events progressed. The proportions of MPs < 1 mm in rainfall (38.0 %) and rainwater runoff (44.5 %) were the largest. Average MPs abundance was the highest in rainwater runoff from the main road area and lowest in the office area (p < 0.05). The abundance of polyester fibers in rainwater runoff from the residential area was significantly higher than that in other areas, while the main road area had the highest abundance of films (p < 0.05). Overall, 72 % of MPs in rainfall were fibers, and most were composed of polyester, while the MPs in rainwater runoff were mainly fragments (41.2 %) and fibers (35.3 %) composed mainly of polypropylene, polyethylene, and polyester. This study shows that urban pipeline rainwater runoff is one of the main pathways for land-based MPs transport to surface waters, and provides a scientific reference for preventing and controlling MPs entering water bodies through rainwater pipelines.

Novel antimicrobial and self-healing dental resin to combat secondary caries and restoration fracture.

OBJECTIVE: Dental resin composites have been the most popular materials for repairing tooth decay in recent years. However, secondary caries and bulk fracture are the major hurdles that affect the lifetime of dental resin composites. This current study synthesized a novel antimicrobial and self-healing dental resin containing nanoparticle-modified self-healing microcapsules to combat secondary caries and restoration fracture. METHODS: Multifunctional dental resins containing 0-20% nanoparticle-modified self-healing microcapsules were prepared. The water contact angle, antimicrobial properties, mechanical properties, cell toxicity, and self-healing capability of the dental resins were tested. RESULTS: A novel multifunctional dental resin was synthesized. When the microcapsule mass fraction was 10%, the resin presented a strong bacteriostasis rate (80.3%) and excellent self-healing efficiency (66.1%), while the hydrophilicity, mechanical properties, and cell toxicity were not affected. SIGNIFICANCE: The novel antimicrobial self-healing dental resin is a promising candidate for use in clinical practice, which provides a simple and highly efficient strategy to combat secondary caries and restoration fracture. This novel dental resin also gives the inspiration to prolong the service life of dental restorations.

Novel low-shrinkage dental resin containing microcapsules with antibacterial and self-healing properties.

Dental resin restorations commonly fail because of fractures and secondary caries. The aim of this research was to synthesize a novel low-shrinkage dental resin with antibacterial and self-healing properties. The low-shrinkage dental resin was obtained by incorporating a 20 wt% anti-shrinkage mixture of an expanding monomer 3,9-diethyl-3,9-dimethylol -1,5,7,11-tetraoxaspiro[5,5] undecane and an epoxy resin monomer diallyl bisphenol A diglycidyl ether (1:1, referred as "UE") and different mass fractions of self-healing antibacterial microcapsules (0%, 2.5%, 5%, 7.5%, and 10%) were incorporated into the matrix to prepare multifunctional dental resin. Polymerization shrinkage, mechanical properties, antibacterial activity, self-healing ability, and cytotoxicity of this dental resin were evaluated. The polymerization volumetric shrinkage of resin containing 20 wt% UE and 7.5 wt% microcapsules was reduced by 30.12% (4.13% ± 0.42%) compared with control. Furthermore, it exhibited high antibacterial activity and a good self-healing efficiency of 71% without adversely affecting the mechanical property and cell viability. This novel multifunctional dental resin with low polymerization shrinkage and excellent antibacterial activity and self-healing capability has potential application as a dental resin material to decrease the incidence of fractures and secondary caries.

Long-term application of organic compost is the primary contributor to microplastic pollution of soils in a wheat-maize rotation.

Microplastics (MPs) are posing new threats to soil ecosystems. Organic fertilizers are considered as an emerging contributor to MPs accumulation in agricultural soils. However, few studies have focused on the MPs fate in soils under long-term organic fertilizer application. Based on an 11-year field test with wheat-maize cropping rotation, this study investigated the characteristics of MPs in pig manure and cow manure composts, and examined the impact of long-term compost application on soil MPs accumulation, surface morphology, and distribution. The MPs contents in pig manure and cow manure composts were 3547 and 4520 items kg-1, respectively. Microplastics abundances in soils under long-term use of these two composts were 144 to 287 and 140 to 316 items kg-1, respectively, which increased significantly with increasing compost application amount and was substantially higher than that in soils without compost. Accumulated soil MPs sourced from long-term compost application were 1.73 × 108 to 7.22 × 108 items ha-1, accounting for 43.0 %-75.9 % of the total, and the contribution value doubled as the compost application rate doubled. The proportion of MPs <1 mm in composts (31.0 %) was lower when compared with that in compost-amended soils (43.8 %), and size and abundance reduced with increasing soil depth. Microplastics shapes and polymer types in composts and compost-amended soils were similar and mostly included fragments of polyethylene and polypropylene and fibers of polyethylene terephthalate. Microplastics in compost-amended soils showed complicated weathered surface morphologies, and soil mineral colloids were attached. These results demonstrate that compost-derived MPs in soils can be gradually weathered and degraded into smaller particles under long-term compost application. These findings provide key insights into the pollution level of soil MPs with organic fertilizer application and serve as a scientific basis for developing MPs mitigation measures in agricultural soils.

Microplastics promoted cadmium accumulation in maize plants by improving active cadmium and amino acid synthesis.

Combined pollution from microplastics (MPs) and cadmium (Cd) can influence soil environment and soil biota, altering plant growth and development, and Cd mobilization. We investigated the effects of polystyrene (PS) and polypropylene (PP) MPs alongside Cd on soil Cd bioavailability, rhizosphere soil metabolomics, bacterial community structure, and maize (Zea mays L.) growth in two soil types (red soil and cinnamon soil). Although the addition of PS/PP-Cd promoted Cd accumulation in maize plants overall, there were large-particle-size- and small-particle-size-dependent effects in the red soil and cinnamon soil, respectively. The difference is mainly due to the capacity of the large particle size MPs to significantly reduce soil pH, improve soil electrical conductivity (EC), promote active Cd, and intensify Cd mobilization in red soil. In contrast, small-size MPs in cinnamon soil promoted the synthesis and secretion of rhizosphere amino acids and soil metabolites, thus promoting Cd absorption by maize roots. Soil microorganisms also improved Cd bioavailability via C-related functional bacteria. Overall, our study provides novel insights on the potential effects of combined MPs and Cd pollution on soil ecology and agricultural production, enhancing our understanding of rhizosphere metabolites in different soils.

Microplastic pollution and the related ecological risks of organic composts from different raw materials.

Organic composts are considered emerging contributors to microplastics (MPs) accumulation in agricultural soils. However, MPs pollution in organic compost from different raw materials is unknown. This study investigated MPs occurrence and characteristics in 124 organic compost samples, including single feedstock (livestock manure, poultry manure, crop straw, and solid waste) and compound organic composts, and quantitatively assessed related ecological risks of MPs pollution. The highest and lowest MPs abundances were observed in solid waste (6615 items kg-1) and crop straw (1500 items kg-1) composts, respectively. Compost MPs were mainly 0.5-1 mm (39.5%), colorful polypropylene and polyethylene fragments and films, and polyethylene terephthalate fibers, and the input to farmland soils was 6.96 × 107 to 1.88 × 108 items ha-1 yr-1. Regardless of feedstock, compost-based MPs of different shapes exhibited complicated weathering morphologies and adhered to some mineral colloids. The highest and lowest MPs-induced risk indices in solid waste (H = 134.3) and crop straw (H = 8.9) composts yielded hazard levels IV (high risk) and II (low risk), respectively, due to the different abundance of polymers with diverse hazard scores. These findings provide insights into MPs pollution in organic composts and a theoretical basis for the safe production and application of compost.

Reusable and Practical Biocomposite Based on Sphingopyxis sp. YF1 and Polyacrylonitrile-Based Carbon Fiber for the Efficient Bioremediation of Microcystin-LR-Contaminated Water.

Microbial degradation is a cost-effective and environmentally friendly method for removing microcystin-LR (MC-LR). However, the application of free bacteria has limitations due to low operational stability and difficulties in recovery. In a previous study, our group successfully isolated a highly efficient MC-LR-degrading bacterium, Sphingopyxis sp. YF1, from Taihu. To enhance its practical potential in addressing MC-LR-contaminated water pollution, a novel biological material named polyacrylonitrile-based carbon fiber @Sphingopyxis sp. YF1 (PAN-CF@YF1) was synthesized. The immobilization conditions of strain Sphingopyxis sp. YF1 on PAN-CF surfaces were optimized using Box-Behnken design and response surface methodology (RSM), which turned out to be an optimal pH of 7.6 for the culture medium, a ratio of 0.038 g of supporting materials per 100 mL of culture media, and an incubation time of 53.4 h. The resultant PAN-CF@YF1 showed a great degradation effect both for low and high concentrations of MC-LR and exhibited satisfactory cyclic stability (85.75% after six cycles). Moreover, the application of PAN-CF@YF1 in the bioreactors demonstrated effective and sustainable MC-LR removal, with a removal efficiency of 78.83% after three consecutive treatments. Therefore, PAN-CF@YF1 with high degradation activity, environmental compatibility, straightforward preparation, and recyclability shows significant application potential for the bioremediation of MC-LR-contaminated water bodies.

Association between groups of immunoglobulin G antibodies against periodontal microorganisms and diabetes-related mortality.

BACKGROUND: Immunoglobulin G (IgG) antibodies against periodontal microorganisms can be markers of periodontal infection because their levels rise following infection and remain elevated several years later. METHODS: We evaluated the relationship between groups of IgG antibodies against 19 periodontal microorganisms and diabetes-related mortality over 27 years among participants of the National Health and Nutrition Examination Survey III (1988 to 1992) aged ≥40 years at the time of examination (N = 8,153). RESULTS: Individuals in the highest versus lowest antibody tertiles were at 86% higher risk of dying due to diabetes-related causes in the Red-Green antibody cluster (T. forsythia, T. denticola, A. actinomycetemcomitans, E. corrodens, S. noxia, V. parvula, C. rectus) (hazard ratio [HR], 1.86; 95% CI, 1.09 to 3.20) and 55% lower in the Orange-Blue antibody cluster (E. nodatum, A. naeslundii) (HR, 0.45, 95% CI, 0.32 to 0.63) in multivariable models. In these models, individuals with diabetes at the time of examination had a 16-fold higher risk of dying due to diabetes-related causes (HR, 16.4; 95% CI, 11.0 to 24.7). CONCLUSION: As a subset of periodontal microorganisms are associated with adverse systemic outcomes, antibody profiles may help in prediction of diabetes-related mortality and identify subgroups of individuals among whom periodontal treatment may impact diabetes-related outcomes.

Novel antibacterial dental resin containing silanized hydroxyapatite nanofibers with remineralization capability.

OBJECTIVES: Secondary caries is the primary issue that causes restoration failure. The objectives of this study were to: (1) synthesize silanized hydroxyapatite nanofibers loaded with erythromycin (s-HAFs@EM); (2) evaluate the mechanical property, antibacterial activity, and remineralization capability of the novel dental resin containing s-HAFs@EM. METHODS: s-HAFs were prepared by the solvothermal approach and loaded with EM. Characterization and antibacterial activity were evaluated. Subsequently, s-HAFs@EM were incorporated into dental resin at different mass fractions (5 %, 10 %, 15 %, and 20 %), and then they were submitted to characterization, including mechanical property, antibacterial activity, remineralization capability, and cytotoxicity. RESULTS: s-HAFs@EM were successfully synthesized, and they exhibited excellent antibacterial activity. Resin containing 15 % s-HAFs@EM exhibited the best flexural strength (118.67 ± 15.71 MPa) and elastic modulus (2.02 ± 0.30 GPa) (P < 0.05), which were increased by 65.43 % and 90.7 %, compared to those of neat resin, respectively. Resin with 15-20 % s-HAFs@EM showed high antibacterial rate (>85 %) when compared control group (P < 0.05). Furthermore, resin also exhibited a definite remineralization capability and good biosafety in vitro. SIGNIFICANCE: This novel multifunctional resin with improved mechanical property, desirable antibacterial activity and remineralization capability is promising to combat secondary caries.

Typical microplastics in field and facility agriculture dynamically affect available cadmium in different soil types through physicochemical dynamics of carbon, iron and microbes.

Combined pollution from microplastics (MPs) and other environmental pollutants has attracted considerable attention. Few studies have investigated the effects of polyurethane (PU) and polypropylene (PP) MPs on available Cadmium(Cd) in different soil types. Here, PU and PP additions affected available Cd and reduced its concentration in soil (P > 0.05). PU and PP reduced available Cd more strongly in clay soil than that in sandy soil. PU and PP improved the soil porous structure and voids and significantly increased the Zeta potential in clay soil (P < 0.05). Dissolved organic carbon and pH in clay soil were significantly negatively correlated with available Cd after PU and PP addition, and Fe(Ⅱ) was significantly negatively correlated with available Cd in sandy soil. PU and PP addition promoted the C-C, CO32-, and C-H functional groups and FeO, FeOOH, and Fe3O4 formation and influenced the effective Cd through adsorption and precipitation. CdCO3 formation and clay mineral adsorption, and iron oxide formation, influenced the effective Cd in clay and sandy soils, respectively. PU and PP influenced the effective state of Cd by affecting bacterial communities related to carbon and iron cycles. This study is significant for assessing the environmental risks of MPs combined with heavy metals in different soils and their mechanisms.

How do controlled-release fertilizer coated microplastics dynamically affect Cd availability by regulating Fe species and DOC content in soil?

Microplastics (MPs) affect the accumulation of heavy metals by regulating the soil environment. However, studies on the dynamic effects of microplastics on the available states of heavy metals in soil are lacking. In particular, how controlled-release fertilizer coated microplastics can synergistically change the avsilable states of heavy metals in soil by affecting soil physical and chemical properties and microbial community structure is still lacking. The dynamic effect of polyurethane (PU) MPs on the effective state of soil cadmium (Cd; DGTCd), at different particle sizes and concentrations, was studied in situ by diffusive gradient in thin-films (DGT) for the first time. The bioavailability, soil chemical properties, and microbial effects of PU MPs on Cd depend on PU particle size and concentration; high-concentration (1 %) PU MPs cause a significant increase in DGT-Cd concentration. The addition of PU MPs decreased soil pH and dissolved organic carbon (DOC), while increasing the absolute zeta value, Fe(II) and Mn(II), in a manner dependent on particle size, concentration, and culture time. Correlation analysis combined with path analysis showed that PU MPs affected the effective state of Cd by changing soil properties, among which Fe(II) content and DOC were important factors controlling the activation of Cd. Meanwhile, changes in soil properties and heavy metal availability correlated significantly with microbial community composition, suggesting that PU MPs may indirectly impact heavy metal activity by affecting microorganisms and functional genes associated with C and Fe cycling. Therefore, when the concentration of PU MPs is higher than 1 %, we should strengthen ecological risk prevention and control of the compound pollution of controlled-release fertilizer coated microplastics and heavy metals in farmland soil.

Serotonergic Neurons in the Brain and Gnathal Ganglion of Larval Spodoptera frugiperda.

The fall armyworm Spodoptera frugiperda (S. frugiperda) (Lepidoptera: Noctuidae) is a worldwide, disruptive, agricultural pest species. The larvae of S. frugiperda feed on seedling, leave, and kernel of crops with chewing mouthparts, resulting in reduced crop yields. Serotonin is an important biogenic amine acting as a neural circuit modulator known to mediate lots of behaviors including feeding in insects. In order to explore the serotonergic neural network in the nervous system of larval S. frugiperda, we performed immunohistochemical experiments to examine the neuropil structure of the brain and the gnathal ganglion with antisynapsin and to examine their serotonergic neurons with antiserotonin serum. Our data show that the brain of larval S. frugiperda contains three neuromeres: the tritocerebrum, the deutocerebrum, and the protocerebrum. The gnathal ganglion also contains three neuromeres: the mandibular neuromere, the maxillary neuromere, and the labial neuromere. There are about 40 serotonergic neurons in the brain and about 24 serotonergic neurons in the gnathal ganglion. Most of these neurons are wide-field neurons giving off processes in several neuropils of the brain and the gnathal ganglion. Serotonergic neuron processes are mainly present in the protocerebrum. A pair of serotonergic neurons associated with the deutocerebrum has arborizations in the contralateral antennal lobe and bilateral superior lateral protocerebra. In the gnathal ganglion, the serotonergic neuron processes are also widespread throughout the neuropil and some process projections extend to the tritocerebrum. These findings on the serotonergic neuron network in larval S. frugiperda allow us to explore the important roles of serotonin in feeding and find a potential approach to modulate the feeding behavior of the gluttonous pest and reduce its damage.

Genipin and insulin combined treatment improves implant osseointegration in type 2 diabetic rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. METHODS: Streptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. RESULTS: The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. CONCLUSION: Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Mussel-inspired PLGA/polydopamine core-shell nanoparticle for light induced cancer thermochemotherapy.

Most photothermal converting systems are not biodegradable, which bring the uneasiness when they are administered into human body due to the uncertainty of their fate. Hereby, we developed a mussel-inspired PLGA/polydopamine core-shell nanoparticle for cancer photothermal and chemotherapy. With the help of an anti-EGFR antibody, the nanoparticle could effectively enter head and neck cancer cells and convert near-infrared light to heat to trigger drug release from PLGA core for chemotherapy as well as ablate tumors by the elevated temperature. Due to the unique nanoparticle concentration dependent peak working-temperature nature, an overheating or overburn situation can be easily prevented. Since the nanoparticle was retained in the tumor tissue and subsequently released its payload inside the cancer cells, no any doxorubicin-associated side effects were detected. Thus, the developed mussel-inspired PLGA/polydopamine core-shell nanoparticle could be a safe and effective tool for the treatment of head and neck cancer. STATEMENT OF SIGNIFICANCE: The described EGFR targeted PLGA/polydopamine core-shell nanoparticle (PLGA/PD NP) is novel in the following aspects: Different from most photothermal converting nanomaterials, PLGA/PD NP is biodegradable, which eliminates the long-term safety concerns thwarting the clinical application of photothermal therapy. Different from most photothermal nanomaterials, upon NIR irradiation, PLGA/PD NP quickly heats its surrounding environment to a NP concentration dependent peak working temperature and uniquely keeps that temperature constant through the duration of light irradiation. Due to this unique property an overheating or overburn situation for the adjacent healthy tissue can be easily avoided. The PLGA/PD NP releases its payload through detaching PD shell under NIR laser irradiation. The EGFR-targeted doxorubicin-loaded PLGA/PD NP effectively eradicate head and neck tumor in vivo through the synergism of photothermal therapy and chemotherapy while not introducing doxorubicin associated cardiotoxicity.