Polystyrene microplastics induce myocardial inflammation and cell death via the TLR4/NF-κB pathway in carp.

Microplastics (MPs) have attracted widespread attention as an emerging environmental pollutant. Especially in aquatic ecosystems, the harm of MPs to aquatic animals has increasingly become a severe environmental problem. In this study, we constructed a carp polystyrene microplastics (PS-MPs) exposure model to explore the damage and mechanism of PS-MPs exposure to carp myocardial tissue. The results of H&E, TUNEL, and AO/EB staining showed that PS-MPs exposure could induce inflammation, apoptosis, and necrosis in carp myocardial tissue and cardiomyocytes. In addition, our study explored the targeting relationship between PS-MPs and TLR4 and found that PS-MPs exposure could significantly increase the expression of TLR4 pathway-related factors. As the concentration of PS-MPs increased, the NF-κB pathway and inflammation-related factors increased dose-dependent. In addition, myocardial injury induced by exposure to PS-MPs was predominantly apoptotic, accompanied by necrosis. In short, our data suggest that PS-MPs cause damage to myocardial tissue via the TLR4\NF-κB pathway. The above findings enrich the theory of toxicological studies on PS-MPs and provide an essential reference for aquaculture.

Analysis of percutaneous kyphoplasty under different types of anesthesia for the treatment of multiple osteoporotic vertebral fractures.

BACKGROUND: Surgeons recognize that using percutaneous kyphoplasty (PKP) under local anesthesia to treat osteoporotic vertebral fracture (OVF) prevents interference with the general situation of elderly patients suffering from multiple organ dysfunction. Surgeons can directly assess whether nerve injury occurs while the patient is awake. However, when patients with multiple osteoporotic vertebral fractures (m-OVFs) receive local anesthesia, fluoroscopy time often has to be increased, the operative time has to be extended, or the operation has to be terminated because of discomfort related to body posture. No relevant study has thus far been conducted on the type of anesthesia to administer to patients undergoing PKP for m-OVFs. This study aimed to determine which of the two types of anesthesia is more suitable for PKP for m-OVFs. METHODS: A retrospective study was conducted involving 159 patients who underwent PKP for m-OVFs from January 2016 to January 2020; 81 patients underwent PKP under general anesthesia (Group G), and 78 patients underwent PKP under local anesthesia (Group L). Clinical and adverse events were compared between the two groups. RESULTS: The intraoperative mean arterial pressure, average heart rate, average fluoroscopy times of each vertebral body, and operative time were less in Group G than in Group L. The visual analog scale (VAS) score was significantly lower after than before the operation. The anterior vertebral height (AVH), middle vertebral height (MVH), and kyphotic angle (KA) were significantly improved in both groups postoperatively. The improvement in VAS score, AVH, MVH, and KA in Group G were higher than those in Group L. No significant difference in the incidence of complications was observed between the two groups. CONCLUSION: PKP under either general anesthesia or local anesthesia was reliable. Compared with PKP under local anesthesia, PKP under general anesthesia could more reliably maintain the stability of vital signs, alleviate preoperative pain in patients, and attain a better orthopedic effect. Moreover, the latter does not increase the complications of patients with m-OVFs. However, the high medical expense of PKP under general anesthesia is a factor to consider when choosing the type of anesthesia.

Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease.

Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

A mysterious risk factor for bone cement leakage into the spinal canal through the Batson vein during percutaneous kyphoplasty: a case control study.

BACKGROUND: Percutaneous kyphoplasty (PKP) can effectively treat osteoporotic vertebral compression fractures (OVCFs). Although satisfactory clinical outcomes can be achieved, bone cement leakage remains a primary complication of PKP. Previous studies have found many high risk factors for bone cement leakage into the spinal canal; however, less attention to the posterior wall morphologies of different vertebral bodies may be one reason for the leakage. Here, we investigated the effect of posterior vertebral wall morphology in OVCF patients on bone cement leakage into the spinal canal during PKP. METHODS: Ninety-eight OVCF patients with plain computed tomography (CT) scans and three-dimensional (3D) reconstruction images from T6 to L5 were enrolled. 3D-CT and multiplanar reconstructions (MPR) were used to measure the concave posterior vertebral wall depth (PVWCD) and the corresponding midsagittal diameter of the nonfractured vertebral body (VBSD), and the PVWCD/VBSD ratio was calculated. All subjects were divided into the thoracic or lumbar groups based on the location of the measured vertebrae to observe the value and differences in the PVWCD between both groups. The differences in PVWCD and PVWCD/VBSD between the thoracic and lumbar groups were compared. Three hundred fifty-seven patients (548 vertebrae) who underwent PKP within the same period were also divided into the thoracic and lumbar groups. The maximal sagittal diameter (BCSD), the area of the bone cement intrusion into the spinal canal (BCA), and the spinal canal encroachment rate (BCA/SCA × 100%) were measured to investigate the effect of the thoracic and lumbar posterior vertebral wall morphologies on bone cement leakage into the spinal canal through the Batson vein during PKP. RESULTS: The PVWCDs gradually deepened from T6 to T12 (mean, 4.6 mm); however, the values gradually became shallower from L1 to L5 (mean, 0.6 mm). The PVWCD/VBSD ratio was approximately 16% from T6 to T12 and significantly less at 3% from L1 to L5 (P < 0.05). The rate of bone cement leakage into the spinal canal through the Batson vein was 10.1% in the thoracic group and 3.7% in the lumbar group during PKP. In the thoracic group, the BCSD was 3.1 ± 0.5 mm, the BCA was 30.2 ± 3.8 mm2, and the BCA/SCA ratio was 17.2 ± 2.0%. In the lumbar group, the BCSD was 1.4 ± 0.3 mm, the BCA was 14.8 ± 2.2 mm2, and the BCA/SCA ratio was 7.4 ± 1.0%. The BCSD, BCA and BCA/SCA ratio were significantly higher in the thoracic group than in the lumbar group (P < 0.05). CONCLUSIONS: The PVWCD in the middle and lower thoracic vertebrae can help reduce bone cement leakage into the spinal canal by enabling avoiding bone cement distribution over the posterior 1/6 of the vertebral body during PKP. The effect of the difference between the thoracic and lumbar posterior vertebral wall morphology on bone cement leakage into the spinal canal through the Batson vein in OVCF patients during PKP is one reason that the rate of bone cement leakage into the thoracic spinal canal is significantly higher than that into the lumbar spinal canal.

Microplastics change soil properties, plant performance, and bacterial communities in salt-affected soils.

Microplastics (MPs) are emerging contaminants found globally. However, their effects on soil-plant systems in salt-affected habitats remain unknown. Here, we examined the effects of polyethylene (PE) and polylactic acid (PLA) on soil properties, maize performance, and bacterial communities in soils with different salinity levels. Overall, MPs decreased soil electrical conductivity and increased NH4+-N and NO3--N contents. Adding NaCl alone had promoting and inhibitive effects on plant growth in a concentration-dependent manner. Overall, the addition of 0.2% PLA increased shoot biomass, while 2% PLA decreased it. Salinity increased Na content and decreased K/Na ratio in plant tissues (particularly roots), which were further modified by MPs. NaCl and MPs singly and jointly regulated the expression of functional genes related to salt tolerance in leaves, including ZMSOS1, ZMHKT1, and ZMHAK1. Exposure to NaCl alone had a slight effect on soil bacterial α-diversity, but in most cases, MPs increased ACE, Chao1, and Shannon indexes. Both MPs and NaCl altered bacterial community composition, although the specific effects varied depending on the type and concentration of MPs and the salinity level. Overall, PLA had more pronounced effects on soil-plant systems compared to PE. These findings bridge knowledge gaps in the risks of MPs in salt-affected habitats.

Comparison of the Clinical Efficacy and Bone Cement Distribution Difference Between Kummell's Disease and Osteoporotic Vertebral Compression Fracture After Percutaneous Kyphoplasty.

BACKGROUND: Kummell's disease (KD) and osteoporotic vertebral compression fracture (OVCF) are commonly found in patients with osteoporosis. Several studies have been conducted on bone cement distribution in OVCF or KD; a comparison between the 2 diseases is rarely reported. OBJECTIVES: To compare the clinical efficacy and bone cement distribution difference between KD and OVCFs after percutaneous kyphoplasty (PKP). STUDY DESIGN: This was a retrospective, nonrandomized controlled study. SETTING: Department of Orthopedics from an affiliated hospital. METHODS: From January 2018 to December 2020, 61 patients who underwent PKP surgery for single KD or OVCF and met the inclusion criteria were retrospectively reviewed. All patients were assigned to 2 groups: the KD group and the OVCF group. Clinical and radiologic characteristics, including the bone cement volume, leakage, bone cement dispersion scale, anterior vertebral height (AVH), median vertebral height (MVH), posterior vertebral height (PVH), Cobb angle and Visual Analog Scale (VAS) were analyzed and compared using Mimics three-dimensional (3D) reconstruction images and 3D reconstruction computed tomography, preoperatively, postoperatively, and 2 years after the operation, respectively. The correlations between the bone cement dispersion scale and the VH improvement rate (VHIR), VH change rate (VHCR), VAS improvement rate (VASIR), and follow-up VAS improvement rate (f-VASIR) were also evaluated. RESULTS: The mean follow-up time was 24.0 months. Postoperative VH, Cobb angle, vertebra volume, and VAS score were significantly improved in the 2 groups (P < 0.05). There was no statistical difference in postoperative parameters between the 2 groups. While a strong positive correlation between VHIR and bone cement dispersion scale was observed in the OVCF group (P < 0.01), no significant correlation between VHIR and bone cement dispersion scale was found in the KD group. There was no correlation between VASIR and bone cement dispersion scale in both groups. Compared with postoperation, VH was lower in both groups in later follow-up, and the difference between the 2 groups was statistically significant (P < 0.05). VH, VAS, f-VASIR, and VHCR had a worse manifestation in the KD group than in the OVCF group. However, no significant correlation was found between VHCR, f-VASIR, and bone cement dispersion scale in the 2 groups. LIMITATIONS: This study was limited by the non-randomized design, small sample size, and lack of a comprehensive follow-up period. CONCLUSIONS: Although there was no significant difference in the bone cement distribution and early clinical efficacy between KD and OVCF patients under the same surgical plan and surgeon, OVCF patients exhibited better long-term radiologic and clinical outcomes.

Low-cost dual-energy CBCT by spectral filtration of a dual focal spot X-ray source.

Dual-energy cone beam computed tomography (DE-CBCT) has been shown to provide more information and improve performance compared to a conventional single energy spectrum CBCT. Here we report a low-cost DE-CBCT by spectral filtration of a carbon nanotube x-ray source array. The x-ray photons from two focal spots were filtered respectively by a low and a high energy filter. Projection images were collected by alternatively activating the two beams while the source array and detector rotated around the object, and were processed by a one-step materials decomposition and reconstruction method. The performance of the DE-CBCT scanner was evaluated by imaging a water-equivalent plastic phantom with inserts containing known densities of calcium or iodine and an anthropomorphic head phantom with dental implants. A mean energy separation of 15.5 keV was achieved at acceptable dose rates and imaging time. Accurate materials quantification was obtained by materials decomposition. Metal artifacts were reduced in the virtual monoenergetic images synthesized at high energies. The results demonstrated the feasibility of high quality DE-CBCT imaging by spectral filtration without using either an energy sensitive detector or rapid high voltage switching.

Improving the accuracy of bone mineral density using a multisource CBCT.

Multisource cone beam computed tomography CBCT (ms-CBCT) has been shown to overcome some of the inherent limitations of a conventional CBCT. The purpose of this study was to evaluate the accuracy of ms-CBCT for measuring the bone mineral density (BMD) of mandible and maxilla compared to the conventional CBCT. The values measured from a multi-detector CT (MDCT) were used as substitutes for the ground truth. An anthropomorphic adult skull and tissue equivalent head phantom and a homemade calibration phantom containing inserts with varying densities of calcium hydroxyapatite were imaged using the ms-CBCT, the ms-CBCT operating in the conventional single source CBCT mode, and two clinical CBCT scanners at similar imaging doses; and a clinical MDCT. The images of the anthropomorphic head phantom were reconstructed and registered, and the cortical and cancellous bones of the mandible and the maxilla were segmented. The measured CT Hounsfield Unit (HU) and Greyscale Value (GV) at multiple region-of-interests were converted to the BMD using scanner-specific calibration functions. The results from the various CBCT scanners were compared to that from the MDCT. Statistical analysis showed a significant improvement in the agreement between the ms-CBCT and MDCT compared to that between the CBCT and MDCT.

Effects of microplastics on cadmium accumulation by rice and arbuscular mycorrhizal fungal communities in cadmium-contaminated soil.

Both microplastics (MPs) and cadmium (Cd) are common contaminants in soil-rice systems, but their combined effects remain unknown. Thereby, we explored the effects of three MPs, i.e., polyethylene terephthalate (PET), polylactic acid (PLA), and polyester (PES), on Cd accumulation in rice and the community diversity and structure of arbuscular mycorrhizal fungi (AMF) in soil spiked with or without Cd. Results showed that 2% PLA decreased shoot biomass (-28%), but PET had a weaker inhibitive effect. Overall, Cd alone did not significantly change shoot and root biomass and increased root biomass in combination with 0.2% PES. MPs generally increased soil Cd availability but decreased Cd accumulation in rice tissues. Both MPs and Cd improved the bioavailability and uptake of Fe and Mn in rice roots. MPs altered the diversity and community composition of AMF, depending on their type and dose and co-existing Cd. Overall, 2% PLA caused the most distinct changes in soil properties, plant growth and Cd accumulation, and AMF communities, but showed no synergistic interactions with Cd. In conclusion, MPs can mediate rice performance and Cd accumulation via altering soil properties, nutrient uptake, and root mycorrhizal communities, and biodegradable PLA MPs thought environment-friendly can exhibit higher phytotoxicity than conventional MPs.

Volumetric computed tomography with carbon nanotube X-ray source array for improved image quality and accuracy.

Cone beam computed tomography (CBCT) is widely used in medical and dental imaging. Compared to a multidetector CT, it provides volumetric images with high isotropic resolution at a reduced radiation dose, cost and footprint without the need for patient translation. The current CBCT has several intrinsic limitations including reduced soft tissue contrast, inaccurate quantification of X-ray attenuation, image distortions and artefacts, which have limited its clinical applications primarily to imaging hard tissues and made quantitative analysis challenging. Here we report a multisource CBCT (ms-CBCT) which overcomes the short-comings of the conventional CBCT by using multiple narrowly collimated and rapidly scanning X-ray beams from a carbon nanotube field emission source array. Phantom imaging studies show that, the ms-CBCT increases the accuracy of the Hounsfield unit values by 60%, eliminates the cone beam artefacts, extends the axial coverage, and improves the soft tissue contrast-to-noise ratio by 30-50%, compared to the CBCT configuration.

High performance polypyrrole coated carbon-based electrocatalytic membrane for organic contaminants removal from aqueous solution.

Electrocatalytic filtration process adopting the electrocatalytic membrane as both filtration membrane and active electrode showed great prospect on the organic pollutant removal from water. In this work, a high-performance metal-free polypyrrole (PPy) coated carbon-based electrocatalytic membrane (PPy@CCM) was developed through the facile and controllable electro-polymerization deposition method. Structural properties and electrochemical performance of the prepared PPy@CCM were characterized systematically. The influences of preparation parameters and operational parameters on water treatment performance of PPy@CCM were also investigated. Results indicates that the spherical PPy particles uniformly distributed on the surface of PPy@CCM. Coating with PPy particles can significantly improve the hydrophilicity and electrochemical activity of CCM, therefore PPy@CCM has lower hydraulic resistance and higher water treatment performance than CCM. The phenol and chemical oxygen demand (COD) removal rates obtained by PPy@CCM are up to 99.51% and 89.90%, respectively, under the optimal condition of 2.0 V cell potential, 2.50 g·L-1 Na2SO4, 1.5 ml·min-1 flow rate and 50 mg·L-1 phenol, and only 0.5 kWh·kgCOD-1 energy consumption is consumed. In addition, PPy@CCM also exhibits good treatment performance in different water matrixes. Moreover, PPy@CCM has good stability for several cycle operation and considerable applicability for different types of organic pollutants removal. The oxidation mechanism study reveals that PPy@CCM has both direct and indirect oxidation activity during the electrocatalytic filtration treatment, and the coating of PPy can improve the direct oxidation ability and ·OH yield of CCM.

Immunomodulation Mediated by Azithromycin in Experimental Periapical Inflammation.

INTRODUCTION: The purpose of the present study was to compare the immunomodulatory effect of azithromycin (AZM), ampicillin (AMP), amoxicillin (AMX), and clindamycin (CLI) in vitro and AZM on preexisting periapical lesions compared with AMP. METHODS: The susceptibility of 4 common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disk diffusion assay. Preexisting periapical lesions in C57BL/6J mice were treated with AZM, AMP, or phosphate-buffered saline (PBS). Periapical bone healing and the pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro-computed tomographic and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated nuclear factor kappa B activation and the production of interleukin 1 alpha and tumor necrosis factor alpha was assessed in vitro by luciferase assay and enzyme-linked immunosorbent assay. RESULTS: All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI. AZM significantly attenuated periapical bone loss versus PBS. PBS resulted in widely diffused infiltration of mixed inflammatory cells. By contrast, AZM brought about localized infiltration of neutrophils and M2 macrophages and advanced fibrosis. Although the effect of AMP on bone was uncertain, inflammatory cell infiltration was considerably milder than PBS. However, most macrophages observed seemed to be M1 macrophages. AZM suppressed pathogen-stimulated nuclear factor kappa B activation and cytokine production, whereas AMP, AMX, and CLI reduced only cytokine production moderately. CONCLUSIONS: This study showed that AZM led to the resolution of preexisting experimental periapical inflammation. Our data provide a perspective on host response in antibiotic selection for endodontic treatment. However, well-designed clinical trials are necessary to better elucidate the benefits of AZM as an adjunctive therapy for endodontic treatment when antibiotic therapy is recommended. Although both AZM and AMP were effective on preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect.

Preparation and characterization of cellulose nanofibrils from coconut coir fibers and their reinforcements in biodegradable composite films.

Coconut waste husks were effectively utilized in this study as a promising cellulose source for production of purified coir cellulose (PCC) after multiple treatments, e.g., ultrasonic-assisted solvent immersion, alkaline treatment, bleaching, etc. As to upgrade the self-value of coir cellulose based products and further broaden their applications in light of biorefinery, coir cellulose nanofibrils (CCNF) with an average diameter of 5.6 ± 1.5 nm were prepared by selection of a milder TEMPO-mediated oxidation system (TEMPO/NaClO/NaClO2, pH = 4.8) accompanied by subsequent ultrasonic treatment. The cellulose nanofibrils were comprehensively characterized in terms of their functional groups, crystallinity, morphology, and thermal stability. The potential reinforcement of CCNFs as a filler for biodegradable PVA based films was investigated and the main properties including tensile strength, elongation at break, and thermal stability of CCNF/PVA composite films were significantly enhanced especially when 3% of CCNF (based on dry film weight) was applied.

Endodontic Infection-induced Inflammation Resembling Osteomyelitis of the Jaws in Toll-like Receptor 2/Interleukin 10 Double-knockout Mice.

INTRODUCTION: In general, mice develop chronic and nonhealing periapical lesions after endodontic infection. Surprisingly, we recently found that toll-like receptor 2 (TLR2)/interleukin 10 (IL-10) double-knockout (dKO) mice exhibited acute but resolving osteomyelitislike inflammation. In this study, we examined the kinetics of endodontic infection-induced inflammation in TLR2/IL-10 dKO mice and explored a potential mechanism of periapical wound healing mediated by the hypoxia-inducible factor 1 alpha (HIF-1α) subunit and arginase 1. METHODS: TLR2/IL-10 dKO and wild-type C57BL/6J mice were subjected to endodontic infection in the mandibular first molars. Mice were sacrificed on days 0 (noninfected), 10, and 21 postinfection. The extent of bone destruction, inflammation, bone deposition, and gene expression were determined by micro-computed tomographic imaging, histology, bone polychrome labeling, and microarray analysis. In addition, the effect of blocking endogenous HIF-1α was tested in infected TLR2/IL-10 dKO mice using the specific inhibitor YC-1. RESULTS: Infected TLR2/IL-10 dKO mice exhibited extensive bone destruction and inflammation on day 10 followed by spontaneous periapical wound healing including bone formation and resolution of inflammation by day 21 postinfection. In contrast, WT mice developed increasing chronic periapical inflammation over the 21-day observation period. Gene expression analyses and immunohistochemistry revealed that HIF-1α and arginase 1 were up-regulated in spontaneous wound healing in TLR2/IL-10 dKO mice. Blocking of HIF-1α in TLR2/IL-10 dKO mice using YC-1 resulted in significant inhibition of regenerative bone formation. CONCLUSIONS: The TLR2/IL-10 dKO mouse is a novel model resembling osteomyelitis of the jaws in which HIF-1α and arginase 1 appear to be crucial factors in spontaneous wound healing and bone repair.

Farnesol inhibits development of caries by augmenting oxygen sensitivity and suppressing virulence-associated gene expression inStreptococcus mutans.

Streptococcus mutans is a primary etiological agent of dental caries. Farnesol, as a potential antimicrobial agent, inhibits the development ofS. mutans biofilm. In this study, we hypothesized that farnesol inhibits caries development in vitro and interferes with biofilm formation by regulating virulence-associated gene expression. The inhibitory effects of farnesol to S. mutans biofilms on enamel surfaces were investigated by determining micro-hardness and calcium measurements. Additionally, the morphological changes ofS. mutans biofilms were compared using field emission scanning electron microscopy and confocal laser scanning microscopy, and the vitality and oxygen sensitivity ofS. mutans biofilms were compared using MTT assays. To investigate the molecular mechanisms of farnesol's effects, expressions of possible target genesluxS, brpA, ffh, recA, nth, and smx were analyzed using reverse-transcription polymerase chain reaction (PCR) and quantitative PCR. Farnesol-treated groups exhibited significantly higher micro-hardness on the enamel surface and lower calcium concentration of the supernatants as compared to the-untreated control. Microscopy revealed that a thinner film with less extracellular matrix formed in the farnesol-treated groups. As compared to the-untreated control, farnesol inhibited biofilm formation by 26.4% with 500 µmol/L and by 37.1% with 1,000 µmol/L (P<0.05). Last, decreased transcription levels of luxS, brpA, ffh, recA, nth, and smx genes were expressed in farnesol-treated biofilms. In vitrofarnesol inhibits caries development and S. mutans biofilm formation. The regulation of luxS, brpA, ffh, recA, nth, and smx genes may contribute to the inhibitory effects of farnesol.

Elevated CD14 (Cluster of Differentiation 14) and Toll-Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice.

Apical periodontitis (periapical lesions) is an infection-induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll-like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2/TLR4 double deficient (dKO), and wild-type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection-induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF-kB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency-dependent elevation of CD14 (cluster of differentiation 14), which is a co-receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency-dependent inflammation and tissue destruction in vitro and in vivo. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction. Anat Rec, 299:1281-1292, 2016. © 2016 Wiley Periodicals, Inc.

Hepatotoxicity assessment of Mn-doped ZnS quantum dots after repeated administration in mice.

Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future.

Preparation of a camptothecin prodrug with glutathione-responsive disulfide linker for anticancer drug delivery.

We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol monomethyl ether-block-poly(2-methacryl ester hydroxyethyl disulfide-graft-CPT) (MPEG-SS-PCPT). It formed biocompatible nanoparticles (NPs) with diameters of approximately 122 nm with a CPT loading content as high as approximately 25 wt% in aqueous solution. In in vitro release studies, these MPEG-SS-PCPT NPs could undergo triggered disassembly and much faster release of CPT under glutathione (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor activity, and another anticancer drug, doxorubicin hydrochloride (DOX⋅HCl), could also be introduced into the prodrug with a high loading amount. The DOX·HCl-loaded CPT prodrug could deliver two anticancer drugs at the same time to produce a collaborative cytotoxicity toward cancer cells, which suggested that this GSH-responsive NP system might become a promising carrier to improve drug-delivery efficacy.

Surface charge-switchable polymeric magnetic nanoparticles for the controlled release of anticancer drug.

We develop paclitaxel (PTX) and magnetic nanoparticles (MNPs) coencapsulated, surface charge-switchable, thermosensitive poly(d,l-lactic-co-glycolic acid)-l-lysine-d-galactose (PTX-MNP-PLGA-Lys-Gal) NPs for the controlled release of the anticancer drug. The novel dual signal-responsive nanovehicle is formulated to shield off target at pH 7.4 but bind avidly to tumor cells in acidity, alleviating toxicity and side effects of the drug to normal tissues. The mechanism involves pH-sensitive NPs surface charge switching by the deblocking process of galactose molecules followed by protonation of ε-NH2 in lysine residue at acidic pH. Magnetic hyperthermia under near infrared (NIR) irradiation induced the contraction of PTX-MNP-PLGA-Lys-Gal NPs and, in turn, triggered burst release of PTX. Transmission electron microscopy (TEM), fluorescence microscope analyses, Fourier transform infrared (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), dynamic light scattering (DLS), and ξ-potential analyses were performed to characterize physicochemical properties of the as-prepared NPs. The size range of the globule PTX-MNP-PLGA-Lys-Gal NPs after being prescreened was from 130 to 150 nm under simulated physiological medium. The high encapsulation efficiencies of MNPs and PTX were obtained, reaching 85 and 78 wt % for PTX-MNP-PLGA-Lys-Gal NPs, respectively. The tumor inhibitory rate of 78.8% reflected that the resulting NPs could be promising to treat cancer by specific binding and targeting release drug to tumor.

Gold nanocluster-conjugated amphiphilic block copolymer for tumor-targeted drug delivery.

Two kinds of core-shell structured multifunctional nanocarriers of gold nanoclusters (Au NCs) as core and folate (FA)-conjugated amphiphilic hyperbranched block copolymer as shell based on poly(L-lactide) (PLA) inner arm and FA-conjugated sulfated polysaccharide (GPPS-FA) outer arm (Au NCs-PLA-GPPS-FA) were synthesized for targeted anticancer drug delivery. The structure and properties of Au NCs-PLA-GPPS-FA copolymers were characterized and determined by ¹H NMR spectrum, FT-IR spectra, dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopic (TEM) analyses. The anticancer drug, camptothecin (CPT) was used as a hydrophobic model anticancer drug. In vitro, two kinds of the nanocarriers presented a relatively rapid release in the first stage (up to 1 h) followed by a sustained release period (up to 15 h), and then reached a plateau at pH 5.3, 7.4, and 9.6. The release results indicated that CPT release from two kinds of the nanocarriers at pH 9.6 was much greater than that at both pH 5.3 and 7.4. The cytotoxicity studies showed that the CPT-loaded nanocarriers provided high anticancer activity against Hela cells. Furthermore, nanocarriers gained specificity to target some cancer cells because of the enhanced cell uptake mediated by FA moiety. The fluorescent images studies showed that the nanocarriers could track at the cellular level for advance therapy. The results indicated that the Au NCs-PLA-GPPS-FA copolymers not only had great potential as tumor-targeted drug delivery carrier, but also had an assistant role in the treatment of cancer.