Heterogeneous Integration of Memristive and Piezoresistive MDMO-PPV-Based Copolymers in Nociceptive Transmission with Fast and Slow Pain for an Artificial Pain-Perceptual System.

Nociceptive pain perception is a remarkable capability of organisms to be aware of environmental changes and avoid injury, which can be accomplished by specialized pain receptors known as nociceptors with 4 vital properties including threshold, no adaptation, relaxation, and sensitization. Bioinspired systems designed using artificial devices are investigated to imitate the efficacy and functionality of nociceptive transmission. Here, an artificial pain-perceptual system (APPS) with a homogeneous material and heterogeneous integration is proposed to emulate the behavior of fast and slow pain in nociceptive transmission. Retention-differentiated poly[2-methoxy-5-(3,7-dimethyoctyoxyl)-1,4-phenylenevinylene] (MDMO-PPV) memristors with film thicknesses of 160 and 80 nm are manufactured and adopted as A-δ and C nerve fibers of nociceptor conduits, respectively. Additionally, a nociceptor mimic, the ruthenium nanoparticles (Ru-NPs)-doped MDMO-PPV piezoresistive pressure sensor, is fabricated with a noxiously stimulated threshold of 150 kPa. Under the application of pricking and dull noxious stimuli, the current flows predominantly through the memristor to mimic the behavior of fast and slow pain, respectively, in nociceptive transmission with postsynaptic potentiation properties, which is analogous to biological pain perception. The proposed APPS can provide potential advancements in establishing the nervous system, thus enabling the successful development of next-generation neurorobotics, neuroprosthetics, and precision medicine.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Liposome-assisted enzyme catalysis: toward signal amplification for sensitive split-type electrochemiluminescence immunoassay.

Developing an efficient signal amplification strategy is very important to improve the sensitivity of bioanalysis. In this paper, a liposome-assisted enzyme catalysis signal amplification strategy was developed for electrochemiluminescence (ECL) immunoassay of prostate specific antigen (PSA) in a split-type mode. The sandwich immunoreaction occurred in a 96-well plate, and glucose oxidase (GOx) encapsulated and antibody-modified liposomes were used as labels. The ECL detection was carried out using a rGO-Au NP modified glassy carbon electrode (GCE). The large amount of generated H2O2, i.e. the coreactant of the luminol system, and the excellent catalytic behavior of rGO-Au NPs greatly boosted the ECL signal, resulting in the signal amplification. The developed ECL immunosensor for detecting PSA achieved a wider linear range from 1.0 × 10-13 to 1.0 × 10-8 g mL-1 and a detection limit of 1.7 × 10-14 g mL-1. The application of the proposed strategy was demonstrated by analyzing PSA in human serum samples with recoveries from 89.0% to 113.0%, and relative standard deviations (RSDs) were less than 6.6%. This work provides a new horizon to expand the application of liposomes for ECL bioanalysis.

Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis.

Tumour metastasis is a major cause of cancer treatment failure and death, and chemotherapy efficiency for gastric cancer patients is usually unsatisfactory due to tumour cell metastasis, poor targeting and serious adverse reactions. In this study, a kind of R8GD-modified epirubicin plus tetrandrine liposomes was prepared to enhance the antitumor efficiency via killing tumour cells, destroying tumour metastasis and inhibiting energy supply for tumour cells. In order to investigate the antitumour efficiency of the targeting liposomes, morphology observation, intracellular uptake, cytotoxic effects, and inhibition on tumour metastasis and energy supply were carried out in vitro, and tumour-bearing mice models were established to investigate the antitumour efficiency in vivo. In vitro results showed that R8GD-modified epirubicin plus tetrandrine liposomes with ideal physicochemical properties could kill the most tumour cells, inhibit tumour metastasis and cut-off energy supply for tumour cells. In vivo results exhibited that R8GD-modified epirubicin plus tetrandrine liposomes could enhance the accumulation in tumour site and display an obvious antitumor efficiency. Therefore, R8GD-modified epirubicin plus tetrandrine liposomes could be used as a potential therapy for treatment of gastric cancer.

Enhanced antitumour efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.

RPV-modified epirubicin and dioscin co-delivery liposomes suppress non-small cell lung cancer growth by limiting nutrition supply.

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.

GGP modified daunorubicin plus dioscin liposomes inhibit breast cancer by suppressing epithelial-mesenchymal transition.

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.

Effects of active and passive smoking on salivary cytokines levels in rats: A pilot study.

Cigarette smoking is an established risk factor for some oral diseases. As an essential fluid in the oral cavity, saliva is crucial to maintain oral health. Relative to active smoking, there are very few studies assessing the effect of passive smoking on salivary cytokines levels. In the present study, we established the rat models by the means of the intraoral cigarette smoking or whole body cigarette smoke exposure to simulate human active or passive smoking, respectively. The effects of active or passive smoking on salivary cytokines levels were assessed by using ProcartaPlex multiplex immunoassays. The results of the current study indicated that both active and passive smoking diminished the body weights of rats and increased the levels of some blood counts. Intriguingly, active smoking enhanced the salivary levels of IL-6 and IL-12 p70 and passive smoking elevated the salivary IL-6 level. Moreover, active smoking appeared to have a more prominent activation effect on the salivary IL-6 level. It was noted that active or passive smoking had no significant effect on the salivary IFN-γ level. Active or passive smoking could have potential effects on the salivary levels of some pro-inflammatory cytokines.

The size-dependence and reversibility of polystyrene nanoplastics-induced lipid accumulation in mice: Possible roles of lysosomes.

Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms. The findings indicated that hepatic lipid accumulation was more pronounced in mice exposed to 100 nm PS-NPs compared to 500 nm PS-NPs. This effect was effectively alleviated after 50 days of self-recovery for 100 nm and 500 nm PS-NPs exposure. Mechanistically, although PS-NPs exposure activated autophagosome formation through ERK (mitogen-activated protein kinase 1)/mTOR (mechanistic target of rapamycin kinase) signaling pathway, the inhibition of Rab7 (RAB7, member RAS oncogene family), CTSB (cathepsin B), and CTSD (cathepsin D) expression impaired lysosomal function, thereby blocking autophagic flux and contributing to hepatic lipid accumulation. After termination of PS-NPs exposure, lysosomal exocytosis was responsible for the clearance of PS-NPs accumulated in lysosomes. Furthermore, impaired lysosomal function and autophagic flux inhibition were effectively alleviated. This might be the main reason for the alleviation of PS-NPs-induced lipid accumulation after recovery. Collectively, we demonstrate for the first time that lysosomes play a dual role in the persistence and reversibility of hepatotoxicity induced by environmental relevant doses of NPs, which provide novel evidence for the prevention and intervention of liver injury associated with nanoplastics exposure.

Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation.

BACKGROUND: Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined. METHODS: The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis. RESULTS: Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction. CONCLUSION: Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.

Largely enhanced single-molecule fluorescence in plasmonic nanogaps formed by hybrid silver nanostructures.

It has been suggested that narrow gaps between metallic nanostructures can be practical for producing large field enhancement. We design a hybrid silver nanostructure geometry in which fluorescent emitters are sandwiched between silver nanoparticles and silver island film (SIF). A desired number of polyelectrolyte layers are deposited on the SIF surface before the self-assembly of a second silver nanoparticle layer. Layer-by-layer configuration provides a well-defined dye position. It allows us to study the photophyical behaviors of fluorophores in the resulting gap at the single molecule level. The enhancement factor of a fluorophore located in the gap is much higher than those on silver surfaces alone and on glass. These effects may be used for increased detectability of single molecules bound to surfaces which contain metallic structures for either biophysical studies or high sensitivity assays.

Transforming growth factor-ß1 promotes early odontoblastic differentiation of dental pulp stem cells via activating AKT, Erk1/2 and p38 MAPK pathways.

Background/purpose: TGF-ß1 (Transforming growth factor-ß1) plays an important role in the regeneration and repair of pulp-dentin complex. However, the biological function of TGF-ß1 on odontoblastic differentiation remains unclear, mainly due to the processes of differentiation were controlled by complex signaling pathways. This study aimed to investigate the signaling pathways involved in regulating the early differentiation of dental pulp stem cells (DPSCs) by TGF-ß1 and their functional role. Materials and methods: DPSCs were treated with 1 ng/mL TGF-ß1 and Western blotting was conducted to examine the activation of protein kinase B (AKT), small mothers against decapentaplegic 3 (Smad3), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (Erk1/2). DPSCs were exposed to mineralization medium contained TGF-ß1 with/without the specific signaling pathway inhibitors, and early odontogenic differentiation was evaluated by assessing the expression of alkaline phosphatase (ALP), collagen type 1 alpha 1 (COL1A), dentin matrix protein 1 (DMP-1) and runt-related transcription factor 2 (Runx2). Results: TGF-ß1 stimulated AKT, Smad3, p38 MAPK, Erk1/2 and JNK phosphorylation in DPSCs within 120 min. TGF-ß1 enhanced ALP activity and elevated levels of COL1A, DMP-1 and Runx2. LY294002, U0126 and SB203580 attenuated the effect of TGF-ß1 on DPSCs, however, the SIS3 and SP600125 treated groups had no significant effect. Conclusion: TGF-ß1 promotes the early stage of odontoblastic differentiation in DPSCs by activating AKT, Erk1/2 and p38 MAPK signaling pathways, but not by Smad3 and JNK.

Upper-critical solution temperature (UCST) polymer functionalized nanomedicine for controlled drug release and hypoxia alleviation in hepatocellular carcinoma therapy.

Recently, bioinspired material such as nanoparticle has been successfully applied in the cancer therapy. However, how to precisely control the drug release from nanomedicine in tumor tissue and overcome the hypoxic microenvironment of tumor tissue is still an important challenge in the development of nanomedicine. In this work, a new type of drug-loaded nanoparticles P(AAm-co-AN)-AuNRs@CeO2-DOX (PA-DOX) was prepared by combining high-efficiency photothermal reagents, critical up-conversion temperature polymer layer and anti-cancer drug doxorubicin (DOX) for the treatment of hepatocellular carcinoma (HCC). In this system, CeO2 can decompose hydrogen peroxide to H2O and O2 alleviate the anaerobic microenvironment of liver cancer cells. As a photothermal reagent, AuNRs@CeO2 can convert near-infrared light into heat energy to achieve local heat to kill cancer cells and ablate solid tumors. In addition, the elevated temperature would enable the polymer layer to undergo a phase transition to release more DOX to achieve a controlled release mechanism, which will open up a new horizon for clinical cancer treatment.

Effect of phenol formaldehyde-associated microplastics on soil microbial community, assembly, and functioning.

Increasing investigations explore the effects of plastic pollutants on bacterial communities, diversity, and functioning in various ecosystems. However, the impact of microplastics (MPs) on the eukaryotic community, microbial assemblages, and interactions is still limited. Here, we investigated bacterial and micro-eukaryotic communities and functioning in soils with different concentrations of phenol formaldehyde-associated MPs (PF-MPs), and revealed the factors, such as soil properties, microbial community assembly, and interactions between microbes, influencing them. Our results showed that a high concentration (1%) of PF-MPs decreased the microbial interactions and the contribution of deterministic processes to the community assembly of microbes, and consequently changed the communities of bacteria, but not eukaryotes. A significant and negative relationship was determined between N2O emission rate and functional genes related to nitrification, indicating that the competitive interactions between functional microbes would affect the nitrogen cycling of soil ecosystem. We further found that vegetable biomass weakly decreased in treatments with a higher concentration of PF-MPs and positively related to the diversity of micro-eukaryotic communities and functional diversity of bacterial communities. These results suggest that a high concentration of the PF-MPs would influence crop growth by changing microbial communities, interactions, and eukaryotic and functional diversity. Our findings provide important evidence for agriculture management of phenol formaldehyde and suggest that we must consider their threats to microbial community compositions, diversity, and assemblage in soils due to the accumulation of PF-MPs widely used in the field.

Liposome-assisted chemical redox cycling strategy for advanced signal amplification: A proof-of-concept toward sensitive electrochemiluminescence immunoassay.

This work presents a novel signal amplification strategy for electrochemiluminescence (ECL) biosensor based on liposome-assisted chemical redox cycling for in situ formation of Au nanoparticles (Au NPs) on TiO2 nanotubes (TiO2 NTs) electrode. The system was exemplified by ascorbic acid (AA)-loaded liposome, the redox cycling of AA utilizing tris (2-carboxyethyl) phosphine (TCEP) as reductant, and the use of Au nanoclusters (Au NCs)/TiO2 NTs as working electrode to implement the ECL detection of prostate specific antigen (PSA). Specifically, the AA-loaded liposomes were used as tags to label the captured PSA through a sandwich immunoreaction. After the lysate of the liposome was transferred onto the interface of Au NCs/TiO2 NTs in the presence of Au3+ and TECP, the chemical redox cycling was triggered. In the cycling, Au3+ was directly reduced in situ by AA to form Au NPs on Au NCs/TiO2 NTs electrode, whereas the oxidation product of AA was reduced by TCEP to regenerate AA. The large loading capacity of the liposome and chemical redox cycling resulted in the incomplete reduction of the Au NCs to Au NPs on the TiO2 NTs electrode, enhancing the ECL intensity greatly. The multiple signal amplification strategy achieved an ultrasensitive detection for PSA with a detection limit down to 6.7 × 10-15 g mL-1 and a wide linear concentration range from 1.0 × 10-14 to 1.0 × 10-8 g mL-1. It is believed that this work is anticipated to extend the employment of advanced chemical redox cycling reaction in the field of ECL bioassays.

Amphiregulin regulates odontogenic differentiation of dental pulp stem cells by activation of mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathways.

BACKGROUND: Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs remain largely unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue. METHODS: The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain- and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and the expression of odontoblastic marker proteins after AREG induction were investigated by using Alizarin Red S staining and Western blotting, respectively. RESULTS: AREG (0.01-0.1 µg/mL) treatment of hDPSCs from 1 to 7 days increased hDPSCs growth and affected apoptosis minimally compared with negative controls. AREG exposure significantly promoted hDPSC differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1 µg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSC differentiation while AREG silencing inhibited it. During the differentiation of hDPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. CONCLUSIONS: The data indicated that AREG promoted odontoblastic differentiation and facilitated regeneration and mineralization processes in hDPSCs.

[Microplastic-Induced Alterations to Antibiotic Resistance Genes in Seawater].

The increasing and combined pollution of microplastics (MPs) and antibiotic resistance genes (ARGs) in aquatic environments is a great ecological and health concern. However, MP-induced alterations to ARGs in seawater is poorly understood, impeding risk assessment of plastics. We profiled the diversity and abundance of ARGs and mobile genetic elements (MGEs) in seawater after the addition of three different MPs (PE, PVC, and PVA) and 49-day aerated incubation.A total of 20, 35, 42, and 64 ARGs were detected in BLK, PE, PVC, and PVA, with 2, 4, 2, and 3 MGEs, respectively. The absolute abundance of ARGs in the seawater aerated with MPs ranged from 4.01×106 copies ·L-1 to 1.05×108 copies ·L-1. Additionally, the variety and richness of ARGs and MGEs in PVA were significantly higher than in the original seawater, or the seawater aerated with the other two MPs. This indicates that PVA, which is water soluble, could induce more diverse and abundant ARGs in seawater. Significant correlations among ARGs, MGEs, and 16S rRNA genes were observed, implying that the occurrence of MGEs in seawater may accelerate the transmission of ARGs through horizontal gene transfer, and bacterial microorganisms could directly affect the propagation and dissemination of ARGs.

[Preparation of ibuprofen/sPEG-b-PLLA copolymer microspheres and its in vitro release properties].

Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.