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Chinese medicine has been used for Alzheimer’s disease (AD) treatment for thousands of years with more effective and fewer side effects. Therefore, developing effective potential candidates from Chinese medicine against AD would be considered as critical and efficient therapy for AD treatment. This study was designed to evaluate the neuronal protective effect of fraction n-butanol (NB) of Radix Notoginseng on Aβ25–35-induced PC12 cells, explore the effect of the tested fraction on spatial learning and memory, and characterize the impacts of fraction NB on antioxidant enzymes, Aβ production, and APP and BACE1 expressions. The results revealed that fraction NB could promote proliferation of PC12 cells and protect and rescue PC12 cells from Aβ25–35-induced cell death. Moreover, fraction NB could improve spatial learning and memory impairments of senescence-accelerated prone8 (SAMP8) mice and attenuate oxidative stress and reduce the production of Aβ by inhibiting the expressions of APP and BACE1 in the brains of SAMP8 mice. The result of single dose acute toxicity assay showed that fraction NB had a mild toxicity in vivo. The pronounced actions against AD and in vivo low toxicity of fraction NB suggest that fraction NB may be a useful alternative to the current AD treatment.

Increasing evidence indicates that immune inflammatory processes, especially autoimmune reaction, should be considered in the pathophysiology of schizophrenia and aggressive behavior. The present study aimed to explore the correlation between immune factors (C3 and Th17-related cytokines) and aggressive behavior in schizophrenia patients. Forty schizophrenia patients and forty age- and gender-matched healthy controls participated in the study. Blood samples were assessed by ELISA upon enrollment. Positive and negative syndrome scale (PANSS) and modified overt aggression scale (MOAS) were used to estimate the severity and aggressive symptoms of schizophrenia patients. Plasma levels of IL-17, IL-23, and TGF-β1 in schizophrenia patients were significantly higher than those in healthy controls [(37.63±17.82) vs. (29.34±10.38)pg/ml, p=0.02; (101.40±135.26) vs. (13.09±5.94) pg/ml, p=0.01; (2864.57±2163.61) vs. (1839.69±1797.73)pg/ml, p=0.04], whereas C3 levels were significantly lower in schizophrenia patients [( 120,479.67± 65,612.50) vs. ( 208,060.21± 217,008.21)ng/ml, p=0.02]. IL-17, IL-23, and TGF-β1 levels were positively related to total scores of MOAS (p=0.02, p=0.02 and p=0.03, respectively) and PANSS (p=0.04, p=0.04 and p=0.02, respectively), whereas C3 levels were negatively related to total PANSS scores (p=0.03). IL-17 and IL-23 levels were positively correlated with PANSS excited component scores (p=0.04 and p=0.01, respectively). Our findings suggested that the Th17-related cytokine levels were positively related to the severity of schizophrenia and aggressive behavior, whereas C3 levels were negatively related to the severity of schizophrenia. This study demonstrated that elevated levels of Th17-related cytokines and decreased levels of C3 could be potential biomarkers for schizophrenia and aggressive behavior.

Huntington's disease (HD) is an incurable disease with progressive loss of neural function, which is influenced by epigenetic, oxidative stress, metabolic, and nutritional factors. Targeting inhibition of huntingtin protein aggregation is a strategy for HD therapy, but the efficacy is unsatisfactory. Studies found that selenium (Se) levels in the brain are insufficient for HD disease individuals, while improvement in Se homeostasis in the brain may attenuate neuronal loss and dysfunction. In this study, we applied selenium nanoparticles (NPs) (Nano-Se) for the HD disease therapy by regulating HD-related neurodegeneration and cognitive decline based on transgenic HD models of Caenorhabditis elegans (C. elegans). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected C. elegans from damages in stress conditions. The molecular mechanism further revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and downregulated the expression of histone deacetylase family members at mRNA levels. The results suggested that Nano-Se has great potential for Huntington's disease therapy. In conclusion, the mechanism about how Nano-Se NPs protect from damages in stress conditions and how they repair neural functions will benefit HD disease therapy. This study will also guide rational design of Nano-Se NPs or other selenium compounds to improve HD therapy in the future.

Picobirnaviruses (PBVs) are mostly found in animal alimentary samples. In this study, among 576 respiratory specimens from 476 mammals and 100 chickens, genogroup I PBVs were detected in three cattle and three monkeys, and a genogroup II PBV-positive sample was collected from one cattle specimen. More than one PBV sequence type was observed in two and one genogroup I PBV-positive samples from cattle and monkeys, respectively. Twenty-four complete/near-complete segments 2 (nine from respiratory and 15 from alimentary samples) from the cattle and monkey genogroup I PBVs and one complete segment 2 from the cattle genogroup II PBV were sequenced. Similar to other studies, the cattle PBVs also showed a high diversity. In contrast, the monkey PBVs observed in this study were clustered into three distinct clades. Within each clade, all the sequences showed &gt, 99% amino acid identities. This unique phenomenon is probably due to the fact that monkeys in our locality reside in separated troops with minimal inter-troop contact.

Stilbenes are a group of phytoalexins that play an important role in grapevine (Vitis) basal immunity and can be induced by biotic and abiotic stresses. The levels of chlorophylls, the main pigments in plant cells, can also indicate the tolerance of plants to various stresses. Here, the response of different grapevine genotypes to UV‐C radiation treatment was tested and the abundance of chlorophyll in the Hoe29 and Ke53 genotypes was observed to increase significantly within 6 h of UV‐C treatment. Conversely, chlorophyll levels decreased markedly in the Augster Weiss and Muller–Thurgau genotypes. Furthermore, stilbene abundance increased substantially in the Hoe29, Ke53, Ke83 and Pinot Blanc genotypes, but increased only slightly in Augster Weiss and Muller–Thurgau. The expression of resveratrol synthase, which encodes a key enzyme in the stilbene synthesis pathway, increased in Hoe29, Ke53, Ke83 and Pinot Blanc following UV‐C treatment, in a manner consistent with stilbene accumulation. In addition, we observed that reactive oxygen species (ROS) provide a key trigger in physiological responses and changes in secondary metabolite contents. In summary, the results from this study support a link between ROS, chlorophyll levels and genetic diversity for stilbene abundance in different grape genotypes, providing insights into mechanisms for plant physiological and biochemical responses and adaptations to stress.

Solid polymer electrolyte (SPE) is an important part of printed electrochemical gas sensors and are of value to electrochemical sensors. Here, a new type of SPE was prepared by dissolving a poly-vinylidene fluoride (PVDF) matrix in a 1-methyl-2-pyrrolidone (NMP) to immobilize 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM] [BF4]), which was then used in a new electrochemical amperometric nitrogen dioxide sensor. The SPE was coated on a single electrode and attached to the electrode to construct a simple two-layer structure. Nitrogen dioxide in the air was reduced on the working electrode at a bias voltage of -500 V. We controlled the components and process parameters separately for control experiments. The results show that the SPE based on [EMIM] [BF4], NMP, and PVDF coated on the electrode at a thickness of 1.25 mm with a 1:1:4 weight ratio under heat treatment conditions of 80°C for 2 min has the best sensitivity. The FTIR and XPS results indicated that SPE is prepared via physical miscibility. The SEM and XRD results showed that the sensitivity of the sensor is strongly dependent on the interconnected pore structure in SPE, and the pore structure is related to the synthesis ratio, morphology, and heat treatment mode of SPE. Moreover, the sensor sensitivity has a certain relationship with SPE conductivity. The reaction principle and cycle performance of the sensor were also studied.

Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR-19a-3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor-kappaB (NF-κB) binds to the promoter of miR-19a-3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR-19a-3p inhibits the expression of insulin-like growth factor binding protein-3 (IGFBP-3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR-19a-3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP-3 expression, and which can be inhibited by NF-κB, suggesting an NF-κB/miR-19a-3p/IGFBP-3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.

Despite responses to initial treatment of photodynamic therapy (PDT) being promising, a recurrence rate exists. Thus, finding novel therapeutic targets to enhance PDT efficacy is an urgent need. Reports indicate that connexin (Cx) 40 plays an important role in tumor angiogenesis and growth. However, it is unknown whether Cx40-composed channels have effects on PDT efficacy. The study uniquely demonstrated that Cx40-formed channels could enhance the phototoxicity of PDT to malignant cells in vitro and in vivo. Specifically, Cx40-formed channels at high cell density could increase PDT photocytotoxicity. This action was substantially restricted when Cx40 expression was not induced or Cx40 channels were restrained. Additionally, the presence of Cx40-composed channels enhanced the phototoxicity of PDT in the tumor xenografts. The above results indicate that enhancing the function of Cx40-formed channels increases PDT efficacy. The enhancement of PDT efficacy mediated by Cx40 channels was related with intracellular pathways mediated by ROS and calcium pathways, but not the lipid peroxide-mediated pathway. This work demonstrates the capacity of Cx40-mediated channels to increase PDT efficacy and suggests that therapeutic strategies designed to maintain or enhance Cx40 expression and/or channels composed by Cx40 may increase the therapeutic efficacy of PDT.

Establishing an accurate, simple, and rapid serodiagnosis method aiming for specific cancer antigens is critically important for the clinical diagnosis, therapy, and prognostication of cancer. Currently, surface-enhanced Raman scattering (SERS) readout techniques challenge fluorescent-based detection methods in terms of both optical stability and more importantly multiple detection capability, which become more desirable for clinical diagnostics. We thus started using an interference-free mixing SERS emission (m-SERS) readout to simultaneously indicate, for the first time, three specific liver cancer antigens, including α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and ferritin (FER), even in one clinical serum sample. Here, three triple bonds (C≡N and C≡C) coded SERS tags contribute separate SERS emissions located at 2105, 2159, and 2227 cm–1, respectively; must have one-to-one correspondence from AFP, to FER, to CEA, In the process of detection, the mature double antibody sandwich allows the form...

Background Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain. The exact relationship between increased airborne toxicant exposure and neurological deterioration in the human central nervous system, is still unclear. However, the nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred. Method Computational fluid-particle dynamics modeling of inhaled nanoparticles (1 to 100 nm) under low to moderate breathing conditions (5 to 14 L/min – human; and 0.14 to 0.40 L/min – rat) were performed in physiologically realistic human and rat nasal airways. The simulation emphasized olfactory deposition, and variations in airflow and particle flux caused by the inter-species airway geometry differences. Empirical equations were developed to predict regional deposition rates of inhaled nanoparticles on human and rat olfactory mucosa in sedentary breathing. Considering, breathing and geometric differences, quantified correlations between human and the rat olfactory deposition dose against a variety of metrics were proposed. Results Regional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition ( 3 nm), significantly higher percentage of the inhaled nanoparticles reached rat nasal olfactory than that in human (2 to 32 folds). Taking into account the physical and geometric features between human and rat, the total deposition rate (#/min) and deposition rate per unit surface area (#/min/mm2) were comparable for particles> 3 nm. However, when body mass was considered, the normalized deposition rate (#/min/kg) in the rat olfactory region exceeded that in the human. Nanoparticles

MYB15 promoter of Vitis quinquangularis has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms. China is a center of origin for Vitis and is home to diverse wild Vitis genotypes, some of which show superior pathogen resistance, although the underlying molecular basis for this has not yet been elucidated. In the current study, we identified a transcription factor, MYB15, from the Chinese wild grape, Vitis quinquangularis, whose promoter region (pVqMYB15) was shown to be induced by basal immunity (also called PAMP-triggered immunity, PTI) triggered by flg22, following heterologous expression in Nicotiana benthamiana and homologous expression in grapevine. By analyzing the promoter structure and activity, we identified a unique 283 bp sequence that plays a key role in the activation of basal immunity. In addition, we showed that activation of the MYB15 promoter correlates with differences in the expression of MYB15 and RESVERATROL SYNTHASE (RS) induced by the flg22 elicitor. We further tested whether the MYB15 induction triggered by flg22 was consistent with MYB15 and RS expression following inoculation with Plasmopara viticola in grape (V. quinquangularis and Vitis vinifera) leaves. Mapping upstream signals, we found that calcium influx, an RboH-dependent oxidative burst, an MAPK cascade, and jasmonate and salicylic acid co-contributed to flg22-triggered pVqMYB15 activation. Our data suggest that the MYB15 promoter has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms.

Immunoglobulin G (IgG) is related to the occurrence of many diseases, such as measles and inflammatory. In this paper, IgG imprinted polymers (IgGIPs) were fabricated on the surface of nano Au/nano Ni modified Au electrode (IgGIPs/AuNCs/NiNCs/Au) via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP). The IgGIPs were prepared by IgG conjugated with fluorescein isothiocyanate (FITC-IgG) as both a template and a photocatalyst. After the templates were removed, the photocatalysts (FITC) would not remain in the polymer and avoided all the effect of catalysts on the electrode. The fabricated electrodes were examined by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Under the optimized conditions, IgGIPs/AuNCs/NiNCs/Au was prepared and used as an electrochemical biosensor. The biosensor could be successfully applied for the determination of IgG by differential pulse voltammetry (DPV) measurement. The results showed that the proposed biosensor displayed a broader linear range and a lower detection limit for IgG determination when it was compared to those similar IgG sensors. The linear range from 1.0 × 10−6 mg L−1 to 1.0 × 101 mg L−1 was obtained with a low detection limit (LOD) of 2.0 × 10−8 mg L−1 (S/N = 3). Briefly, the biosensor in this study introduced an easy and non-toxic method for IgG determination and also provided a progressive approach for designing protein imprinted polymers., Graphical abstract Image 1

BackgroundInflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.Methods and analysisThis is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to ‘escitalopram+golimumab (TNF-α inhibitor)’, ‘escitalopram+calcium tablet+vitamin D (PKC activator)’ or ‘escitalopram+placebo’ groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.DiscussionThis study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.Trial registration numberThe trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.

Picobirnaviruses (PBVs) are small non-enveloped bisegmented double-stranded RNA viruses found in humans, mammals, and birds. Increasing molecular epidemiology studies suggest a high sequence diversity of PBVs in numerous hosts and the environment. In this study, using 229 fecal samples from dromedary camels in Dubai, 52.8% were positive for PBVs, of which 77.7% and 41.3% were positive for genogroup I and II, respectively, and 19.0% were positive for both genotypes. Phylogenetic analysis showed high diversity among the sequences of genogroup I and II dromedary PBVs. Marked nucleotide polymorphisms were observed in 75.5% and 46.0% of genogroup I and II RNA-dependent RNA polymerase (RdRp) sequences, respectively, suggesting the co-existence of multiple strains in the same specimen. Both high genetic diversity and prevalence of genogroup I and II PBV in dromedaries were observed. In fact, the prevalence of genogroup II PBV in dromedaries is the highest among all animals to date. The complete/near-complete core genomes of five genogroup I and one genogroup II dromedary PBVs and partial segment 1 and 2 of both genotypes were also sequenced. The dromedary PBV genome organizations were similar to those of other animals. Genetic reassortment and mutation are both important in the ecology and evolution of PBVs.

Interleukin 12 (IL12) is a potent pro-inflammatory chemokine with multifunction, including promoting cytotoxic T-cell-mediated killing of cancer cells. IL12-based cancer gene therapy can overcome IL12's life-threatening adverse effects, but its clinical translation has been limited by the lack of systemic gene-delivery vectors capable of efficiently transfecting tumors to produce sufficient local IL12. Macrophages inherently excrete IL12, and tumor-associated macrophages (TAMs) are the major tumor component taking up a large fraction of the vectors arriving in the tumor. It is thus hypothesized that a gene vector efficiently transfecting both cancer cells and TAMs would make the tumor to produce sufficient IL12; however, gene transfection of TAMs is challenging due to their inherent strong degradation ability. Herein, an IL12 gene-delivery vector is designed that efficiently transfects both cancer cells and TAMs to make them as a factory for IL12 production, which efficiently activates anticancer immune responses and remodels the tumor microenvironment, for instance, increasing the M1/M2 ratio by more than fourfold. Therefore, the intravenously administered vector retards tumor growth and doubles survival in three animal models' with negligible systemic toxicities. This work reports the first nonviral IL12 gene delivery system that effectively makes use of both macrophages and tumor cells.

Objectives To understand persistence of the virus in body fluids and immune response of infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus disease 2019 (COVID-19). Methods We determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction (rRT-PCR), serum antibodies of IgA, IgG and IgM by enzyme linked immunosorbent assay (ELISA), and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China. Results We found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3×106 vs 6.4×104, p, Graphical abstract Image 1

Background: To determine the risk of arterial and venous thromboembolic events (ATEs and VETs) associated with anti-epidermal growth factor receptor (EGFR) agents in non-small-cell lung cancer (NSCLC) patients.Methods: Prospective randomized trials evaluating therapy with or without anti-EGFR agents in NSCLC patients. Data on VTEs and ATEs were extracted.Results: A total of 8,410 patients from 12 trials were included for analysis. Anti-EGFR agents significantly increased the risk of all-grade and high-grade VTEs (Peto OR 1.50, 95%CI 1.16–1.95, P = 0.002; Peto OR 1.73, 95%CI: 1.32–2.26, p < 0.001, respectively), but not for all-grade and high-grade ATEs.Conclusion: The use of anti-EGFR agents significantly increased the risk of all-grade and high-grade VTEs but not for ATEs in NSCLC patients.

Background: Dysregulation of microRNAs (miRNAs) has been found in human epithelial ovarian cancer (EOC). However, the role and mechanism of action of miR-23a in EOC remain unclear. Methods: The roles of miR-23a, IKKα, and ST7L in EOC were determined by MTT, colony formation, wounding healing, transwell, flow cytometry, immunofluorescence, RT–qPCR, and western blotting experiments. miR-23a target genes were validated by EGFP reporter assays, RT–qPCR, and western blotting analysis. Results: miR-23a is upregulated and promotes tumorigenic activity by facilitating the progress of cell cycle and EMT and repressing apoptosis in EOC cells. miR-23a enhances the expression of IKKα but suppresses the expression of ST7L by binding the 3′UTR of each transcript in EOC cells. The proliferation, migration, and invasion of EOC cells are increased by IKKα and inhibited by ST7L. Furthermore, miR-23a activates NF-κB by upregulating IKKα and WNT/MAPK pathway by downregulating ST7L. Conclusions: miR-23a functions as an oncogene by targeting IKKα and ST7L, thus contributing to the malignancy of EOC cells.

Previously, we reported the discovery of a novel canine picornavirus (CanPV) in the fecal sample of a dog. In this molecular epidemiology study, CanPV was detected in 15 (1.11%) of 1347 canine fecal samples from Hong Kong and one (0.76%) of 131 canine fecal samples from Dubai, with viral loads 1.06×10(3) to 6.64×10(6) copies/ml. Complete genome sequencing and phylogenetic analysis showed that CanPV was clustered with feline picornavirus (FePV), bat picornavirus (BatPV) 1 to 3, Ia io picornavirus 1 (IaioPV1) and bovine picornavirus (BoPV), and this cluster was most closely related to the genera Enterovirus and Sapelovirus. The Ka/Ks ratios of all the coding regions were

To gain a better understanding of nanoparticle exposure in human nasal cavities, laboratory animals (e.g. rat) are used for in vivo studies. However, due to anatomical differences between human and rodent nasal cavities, direct particle deposition comparisons between species are difficult. This paper presents a comparative nanoparticle (1 nm, 10 nm, and 100 nm) deposition study using anatomically realistic models of a human and rat nasal cavity. The particle deposition fraction was highest consistently in the main nasal passage, for all nanoparticles tested, in the human model; whereas this was only the case for 10 nm, and 100 nm particles for the rodent model, where greater deposition was found in the anterior nose for 1 nm particles. A deposition intensity (DI) term was introduced to represent the accumulated deposition fraction on cross-sectional slices. A common and preferential deposition site in the human model was found for all nanoparticles occurring at a distance of 3.5 cm inside the nasal passage. For the rodent model maximum DI occurred in the vestibule region at a distance of 0.3 cm, indicating that the rodent vestibule produces exceptionally high particle filtration capability. We also introduced a deposition flux which was a ratio of the regional deposition fraction relative to the region's surface area fraction. This value allowed direct comparison of deposition flux between species, and a regional extrapolation scaling factor was found (e.g. 1/10 scale for vestibule region for rat to human comparison). This study bridges the in vitro exposure experiments and in vivo nanomaterials toxicity studies, and can contribute towards improving inter-species exposure extrapolation studies in the future.

Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C 60 (OH) 22 and Gd@C 82 (OH) 22 ) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C 60 (OH) 22 and Gd@C 82 (OH) 22 . More importantly, Gd@C 82 (OH) 22 are shown to have stronger ability than C 60 (OH) 22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application. From the Clinical Editor The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.

Depressive and anxiety disorders are frequently observed in patients with Systemic Lupus Erythematosus (SLE). However, the underlying mechanisms are still unknown. We conducted this survey to understand the prevalence of depression and anxiety in SLE patients without major neuropsychiatric manifestations (non-NPSLE) and to explore the relationship between emotional disorders, symptoms, autoantibodies, disease activity, and treatments in SLE. 176 SLE patients were included, and SLE disease activity index (SLEDAI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) were recorded to evaluate their disease activity and emotional status. We found that depressive and anxiety disorders were common among SLE patients: 121 (68.8%) patients were in depression status while 14 (8.0%) patients could be diagnosed with depression. Accordingly, 101 (57.4%) were in anxiety status and 21 (11.9%) could be diagnosed with anxiety. Depression was associated with disease activity, and anxiety was associated with anti-P0 antibody, while both of them were associated with proteinuria. HAMA and HAMD scores were in strong positive correlation and they were independent risk factors of each other. We concluded that the high prevalence of depression and anxiety and the association between depression and SLE disease activity might reveal the covert damage of central nervous system in SLE. The role of anti-P0 antibody in SLE patients with emotional disorders warrants more researches.

Indoor air quality has great impact on the human health. An increasing number of studies have shown that printers could release particulate matters and pose adverse effects on indoor air quality. In this study, a thorough investigation was designed to assess the aerosol printer particle total number concentration (TNC) and size distribution in normal office environment, one copy center, and a clean chamber. Particle analyzers, SMPS, OPS, and CPC3007 were used to monitor the total printing process. In normal office environment, 37 laser printers out of all surveyed 55 printers were classified as high particle emitters. Comparing to laser printers, 5 inkjet printers showed no particle emission. Particle emission level in a copy center increased slightly with TNC elevating to about 2 times of the aerosol background. Simulating test in a clean chamber indicated that printer-emitted particles were dominated by particles in nanoscale (diameter of particle, D(p) < 100 nm). These particles in a sealed clean chamber attenuated so slowly that it still held at high level with the concentration of 1.5 x 10(4) particles/cm3 after printing for 2.5 hours. Our present results demonstrate that printers indeed release particulates which keeping at a high concentration level in the indoor environment. Special care should be taken to this kind of widely applied machines and effective controls of particle emission at printing processes are necessary.

A strain-hardening cementitious composite with polyvinyl alcohol (PVA-SHCC) has the characteristic of multiple cracks under tensile load. PVA-SHCC has been utilized to replace ordinary concrete material in this study with the PVA fiber volume as a variation. Five PVA-SHCC and two reinforced concrete (RC) beams were designed to investigate cracking performance under concentrated loads (including crack number, width, spacing, and height). Results of the serviceability limit state showed that cracks on PVA-SHCC beams with fiber volume ratio of 2% were densely distributed, and the maximum crack width did not exceed 0.1 mm. Compared with the RC beams, crack height was reduced by 21.6%−30.9%, and the average crack spacing was reduced by approximately 60%. After the PVA-SHCC beam cracked, the strain on the steel bars did not increase immediately, and the steel bars were considerably coordinated with the deformation of the PVA-SHCC. The reason for this phenomenon is that the addition of randomly distributed PVA fibers effectively limited the expansion of cracks. Given the tensile strain hardening characteristics of PVA-SHCC, the formula for calculating the average crack width of the PVA-SHCC beam is proposed, which can be used for analysis and verification of the crack width of PVA-SHCC beams.

In the current study, we identified a transcription factor, MYB14, from Chinese wild grape, Vitis quinquangularis-Pingyi (V. quinquangularis-PY), which could enhance the main stilbene contents and expression of stilbene biosynthesis genes (StSy/RS) by overexpression of VqMYB14. The promoter of VqMYB14 (pVqMYB14) was shown to be induced as part of both basal immunity (also called pathogen-associated molecular pattern (PAMP)-triggered immunity, PTI) and effector-triggered immunity (ETI), triggered by the elicitors flg22 and harpin, respectively. This was demonstrated by expression of pVqMYB14 in Nicotiana benthamiana and Vitis. We identified sequence differences, notably an 11 bp segment in pVqMYB14 that is important for the PTI/ETI, and particularly for the harpin-induced ETI response. In addition, we showed that activation of the MYB14 promoter correlates with differences in the expression of MYB14 and stilbene pattern induced by flg22 and harpin. An experimental model of upstream signaling in V. quinquangularis-PY is presented, where early defense responses triggered by flg22 and harpin partially overlap, but where the timing and levels differ. This translates into a qualitative difference with respect to patterns of stilbene accumulation.

Background and objective Photodynamic therapy (PDT) has been widely used to treat malignant tumors. Our previous studies indicated that connexin (Cx) 32- and Cx26-composed gap junctional intercellular communication (GJIC) could improve the phototoxicity of PDT. However, the role of heterotypic Cx32/Cx26-formed GJIC in PDT phototoxicity is still unknown. Thus, the present study was aimed to investigate the effect of Cx32/Cx26-formed GJIC on PDT efficacy. Methods CCK8 assay was used to detect cell survival after PDT. Western blot assay was utilized to detect Cx32/Cx26 expression. "Parachute" dye-coupling assay was performed to measure the function of GJ channels. The intracellular Ca2+ concentrations were determined using flow cytometer. ELISA assay was performed to detect the intracellular levels of PGE2 and cAMP. Results The present study demonstrates there is a Cx32/Cx26-formed GJIC-dependent reduction of phototoxicity when cells were exposure to low concentration of Photofrin. Such a protective action is missing at low cell density due to the lack of GJ coupling. Under high-cell density condition, where there is opportunity for the cells to contact each other and form GJ, suppressing Cx32/Cx26-formed GJIC by either inhibiting the expression of Cx32/Cx26 or pretreating with GJ channel inhibitor augments PDT phototoxicity after cells were treated with at 2.5 µg/ml Photofrin. The above results suggest that at low Photofrin concentration, the presence of Cx32/Cx26-formed GJIC may decrease the phototoxicity of PDT, leading to the insensitivity of malignant cells to PDT treatment. The GJIC-mediated PDT insensitivity was associated with Ca2+ and prostaglandin E2 (PGE2 ) signaling pathways. Conclusion The present study provides a cautionary note that for tumors expressing Cx32/Cx26, the presence of Cx32/Cx26-composed GJIC may cause the resistance of tumor cells to PDT. Oppositely, treatment strategies designed to downregulate the expression of Cx32/Cx26 or restrain the function of Cx32/Cx26-mediated GJIC may increase the sensitivity of malignant cell to PDT. Lasers Surg. Med. 51:301-308, 2019. © 2019 Wiley Periodicals, Inc.

Lynch syndrome is a genetically and clinically heterogeneous disorder; it is caused by a germline mutation in DNA mismatch repair (MMR) genes. Individuals with a heterozygous mutation in MLH1 have an increased risk for developing colorectal cancer. Here we described a 5-generation Chinese Lynch syndrome family with different severity and onset age. A novel heterozygous germline mutation (c.3G>T, p.Met1Ile) inMLH1gene was discovered by next generation sequencing. Our study also revealed by qPCR that the MLH1 mRNA expression in peripheral blood of patients in this family was remarkably lower than that of the unaffected carriers and non-carriers. The research results indicated that the mRNA expression level may provide predictive suggestions of treatment and management for carriers with the initiation codon mutation ofMLH1in this family. Further studies are undertaken in this family as well as other families with Lynch syndrome to interrogate the exact reasons affecting the MLH1 mRNA expression level and whether mRNA expression in peripheral blood could be a significant factor for early diagnosis and surveillance of Lynch syndrome.

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.

Weiping Xia,1,2 Rubai Zhou,1 Guoqing Zhao,1 Fan Wang,1 Ruizhi Mao,1 Daihui Peng,1 Tao Yang,1 Zuowei Wang,1,3 Jun Chen,1 Yiru Fang1,4,5 1Division of Mood Disorders, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Medical Psychology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Mood Disorder Department, Hongkou District Mental Health Center of Shanghai, Shanghai, People’s Republic of China; 4State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China Background: Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method.Subjects and methods: DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed.Results: When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group.Conclusion: The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD. Keywords: diffusion tensor imaging, anxious depression, tract-based spatial statistics, micro-structure of whiter matter

It is important to accurately assess the regional spatial distribution and variation of soil carbon and its fractions due to its great significance in soil carbon cycling and soil quality. The objectives of this study were to investigate the spatial variability of soil carbon and its fractions using classical and geostatistical statistics. Topsoil samples (0-20 cm) from 119 sites in Wolfberry Field were collected from a grid of 100 m×100 m in Zhongning County. The GS+7.0 software was used to fit a semivariance model to determine the optimal theoretical model and parameters. The spatial distribution characteristics of soil carbon and its fractions were studied by ordinary kriging. The classical statistical analyses showed that the average concentrations of total carbon, inorganic carbon, organic carbon, active organic carbon, medium active organic carbon, and high active organic carbon were 28.74, 18.72, 10.09, 1.81, 1.48, and 0.73 g·kg

In this paper, an event-triggered synchronization control scheme is developed for a class of chaotic Lur’ e systems with time delays. A novel Lyapunov-Krasovskii functional (LKF) is designed to extend the sampling period of the systems. Moreover, an improved event-triggered mechanism is constructed to decrease the amounts of communication between controller and sensor, and the numbers of controller updates. Based on the Lyapunov stability theory, it is proved strictly that the chaotic Lur'e systems are asymptotically stable with the proposed controller. Finally, a numerical simulation is presented to illustrate the effectiveness of the event-triggered synchronization control strategy.

Solid polymer electrolyte (SPE) is an important part of printed electrochemical gas sensors and are of value to electrochemical sensors. Here, a new type of SPE was prepared by dissolving a poly-vinylidene fluoride (PVDF) matrix in a 1-methyl-2-pyrrolidone (NMP) to immobilize 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM] [BF4]), which was then used in a new electrochemical amperometric nitrogen dioxide sensor. The SPE was coated on a single electrode and attached to the electrode to construct a simple two-layer structure. Nitrogen dioxide in the air was reduced on the working electrode at a bias voltage of −500 V. We controlled the components and process parameters separately for control experiments. The results show that the SPE based on [EMIM] [BF4], NMP, and PVDF coated on the electrode at a thickness of 1.25 mm with a 1:1:4 weight ratio under heat treatment conditions of 80°C for 2 min has the best sensitivity. The FTIR and XPS results indicated that SPE is prepared via physical miscibility. The SEM and XRD results showed that the sensitivity of the sensor is strongly dependent on the interconnected pore structure in SPE, and the pore structure is related to the synthesis ratio, morphology, and heat treatment mode of SPE. Moreover, the sensor sensitivity has a certain relationship with SPE conductivity. The reaction principle and cycle performance of the sensor were also studied.

Silver-containing dressings are widely used for wound care owing to their broad-spectrum microbicidal activity. However, the potential adverse effects on human health emerging from exposure to their active ingredients (silver ions or nanoparticles) have resulted in widespread concerns about their use. The release profiles of various chemical forms of silver (Ag) from silver-containing dressing are closely related to their bioavailability and potential adverse effects on the body. In this research, we demonstrated a tiered experimental approach for systematic characterization and assessment of silver-containing wound dressing, which provides information for risk assessments. The combination of scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray, X-ray photoelectron spectroscopy, and X-ray diffraction allowed for systematic characterization of silver-containing dressings including their morphology, size, composition, valence state, and crystal forms, which have a close relationship with their silver release profile, antimicrobial activity, and potential toxicity. We developed an Ag release experiment using a reciprocating holder method and an ultrafiltration membrane column to separate the silver nanoparticles (AgNPs) and silver ions released from the dressing. Furthermore, by adjusting the Ag-ion concentration in the release media (simulated body fluid) we could effectively eliminate the interference from AgCl particles, which have a similar size to the AgNPs. We used our method to analyze the release profiles and the chemical form of the Ag present in three commercial silver-containing dressings. A large variation in the total Ag content, amount of released Ag-ions, and amount of released AgNPs was observed in the three dressings that were tested. The silver release profiles were highly dependent on the crystal structures, surface coating process, and binding modes. The cytotoxicity assays were consistent with the characterization data. This tiered approach provides valuable information of optimized AgNPs usage and proper manufacturing process for further safe applications. This study establishes a systematic characterization methodology for better understanding of risk assessment of nano-embeded consumer products.

The present study aimed to investigate the anti‑arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A. Furthermore, indices of the thymus and spleen were determined. The anti‑proliferative effects of curculigoside were detected with Cell Counting kit‑8 assays in rheumatoid arthritis‑derived fibroblast‑like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)‑κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen‑induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF‑α, IL‑1β, IL‑6, IL‑10, IL‑12 and IL‑17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration‑dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)‑κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti‑arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF‑κB signaling pathway.

Background Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing. Methods The three size-fractionated ambient particulates were collected from urban Beijing in winter, heavily affected by traffic and coal-fired emissions. The typical morphological and major chemical components of the PM were characterized first. Oxidative stress and expression of DNA methyltransferases (DNMTs) were then examined in vitro and in the lungs of mouse pups 48 h after exposure to PM by oropharyngeal aspiration. When the exposed and control juvenile mice matured to adulthood, an antigen-induced asthma model was established and relevant bio-indices were assessed. Results PM with different granularities can induce oxidative stress; in particular, F1, with the smallest size (

In this paper, it is found by thermogravimetric analysis experiments on the oil shale semi-coke and Zhundong coal that with the increase of mixing ratio, ignition temperature rise unceasingly, burnout temperature drops, maximum combustion rate and average combustion rate decreases. As the increase of mixing ratio increases, the difficulty of the reaction increases, and the alkali metal elements in the coal are helpful to the reaction. As the mixing ratio increases, the activation energy increases, the difficulty of the reaction increases, and the alkali metal elements in the coal are helpful to the reaction. The increase of the difficulty of reaction indicates that the escape quantity of alkali metal elements is reduced, the effect of the reaction reduces, and the alkali metal are fixed. Therefore, the semi-coke of oil shale and Zhundong coal has certain feasibility.

Zhundong coal has the advantages of low ignition temperature and high burning rate etc,but the high content of alkali metal in coal leads to slagging and fouling problems in the combustion process. In order to improve the coal’s slagging and fouling problems and the combustion efficiency of oil shale semi coke, XRF was used to determine the ash content of the sample to show high sodium content in coal has reached 6.41% and high silicon, aluminum content in the oil shale semi coke and alkali metal content decreased obviously after mixing. By calculating the index of slagging and contamination showed that blending oil shale semi-coke makes slagging, contamination index of Zhundong coal decrease for higher, moderate and slight degree by severity, and semi-coke mixing proportion reached more than 30%, oil shale semi-coke greatly improve the coal contamination problem.

Quasi-East coal is a very low ash, special low sulfur, high calorific value (high calorific value), low quality of the quality of natural clean coal. However, due to the characteristics of coal itself, quasi-East coal used in the power plant is the biggest factor for coking, pollution and pollution caused by fouling. The high alkali metal content in the ash composition is the biggest cause of boiler slagging, contamination and fouling. This chapter aims at the characteristics of quasi-east coal to carry out the quasi-east coal and oil shale semi-coke of the fluidized bed mixed combustion test. The results show that the effect of bed temperature on the efficiency of fluidized combustion is very significant, and the mixing ratio has a significant effect on the effect of fluidized combustion.

Anthropogenic carbon nanotubes, with a fibrous structure and physical properties similar to asbestos, have recently been found within human lung tissues. However, the reported carbon-nanotube-elicited pulmonary pathologies have been mostly confined to inflammatory or neoplastic lesions in the lungs or adjacent tissues. In the present study, we demonstrate that a single pulmonary exposure to multi-walled carbon nanotubes dramatically enhances angiogenesis and the invasiveness of orthotopically implanted mammary carcinoma, leading to metastasis and rapid colonization of the lungs and other organs. Exposure to multi-walled carbon nanotubes stimulates local and systemic inflammation, contributing to the formation of pre-metastatic and metastatic niches. Our study suggests that nanoscale-material-elicited pulmonary lesions may exert complex and extended influences on tumour progression. Given the increasing presence of carbon nanotubes in the environment, this report emphasizes the urgent need to escalate efforts assessing the long-term risks of airborne nanomaterial exposure in non-lung cancer progression.

Background: Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Methods: The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. Outcomes: We found decreased instead of increased DMN FC in MDD compared to NCs. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration or severity. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. Interpretation: We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. All the R-fMRI indices have been made publicly available via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal MDD studies and to other psychiatric disorders. Funding Statement: This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031 and 81371488), the Hundred Talents Program of the Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152 and Z171100000117016), Department of Science and Technology, Zhejiang Province (2015C03037). Declaration of Interests: All the authors declare no competing financial interests. Ethics Approval Statement: All contributed data were from studies approved by local Institutional Review Boards. Data submitted to the consortium were fully deidentified and anonymized.

Background Immune system dysregulation is critical in the physiopathology of major depressive disorder (MDD) and bipolar disorder (BD). However, it is unclear whether both diseases present the same inflammatory patterns during depressive episodes. We explored the differences in pro- and anti-inflammatory cytokines between unipolar and bipolar depression (BDD) and the trajectory of these cytokines after acute-phase treatment. Methods Sixty-four MDD patients, 61 BDD patients, and 62 healthy controls (HCs) were enrolled. We assessed the clinical features and cytokines plasma levels at baseline and week 12. The pro-inflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokines (IL-4, IL-13) of all subjects were assessed by multiplexed sandwich ELISA-based quantitative arrays. Results Before acute-phase treatment, the initial levels of TNF-α and IL-13 were significantly lower in the BDD patients than in the MDD patients. The results demonstrated that there was no relationship between each cytokine level and clinical features of unipolar and bipolar depressions. After 12 weeks, TNF-α, IL-4, and IL-13 levels became lower in MDD patients than in the other two groups regardless of the patients’ response to treatment while the levels of TNF-α and IL-4 increased only in the BDD responders. Limitations The effects of different drugs on inflammatory cytokines in MDD or BDD could not be explored further due to the relatively small sample size. Conclusion Even within the same depressive states, MDD and BDD patients present different inflammatory features, particularly in regard to pro-inflammatory TNF-α and anti-inflammatory IL-13. In addition, the fluctuations of cytokines induced by medication may provide a hint regarding the prediction of treatment response.

Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare type of odontogenic carcinoma that arises within the jaws. PIOSCC has no initial connection with oral mucosa and possibly develops from the residues of the odontogenic epithelium or from an odontogenic cyst or tumor. The diagnosis of PIOSCC can be difficult as it must be differentiated from other odontogenic carcinomas, such as malignant ameloblastoma, from SCCs arising from the overlying oral mucosa, from the primary tumors of the maxillary sinus or nasal mucosa, and from the tumors that have metastasized to the jaws from other primary sites. The present study reported a rare case of a 59-year-old male patient with a course of keratocystic odontogenic tumor for 25 years, between 1988 and 2013, which eventually transformed into PIOSCC after at least five recurrences and corresponding treatments. The mandible excision and titanium plate reconstruction was performed. Follow-up examinations have revealed no sign of recurrence thus far. The present study discussed this case from three aspects of clinical history, radiological examination and pathological features.

To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information on intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag(0))n, to Ag(+) ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity in metallic nanoparticles.

Fullerene derivatives have attracted extensive attention in biomedical fields and polyhydroxyl fullerene (fullerenol), a water-soluble fullerene derivative, is demonstrated as a powerful antioxidant. To further assess their anti-aging and anti-stress potential, we employed Caenorhabditis elegans (C elegans) as a model organism to evaluate the effects of fullerenol on the growth, development, behavior and anti-stress ability in vivo. The data show that fullerenol has no obviously toxic effect on nematodes and can delay C elegans aging progress under normal condition. Further studies demonstrate that fullerenol attenuates endogenous levels of reactive oxygen species and provides protection to C elegans under stress conditions by up-regulating stress-related genes in a DAF-16 depend manner and improving lifespan. In summary, our data suggest that fullerenol might be a safe and reasonable anti-aging candidate with great potential in vivo. (C) 2014 Elsevier Ltd. All rights reserved.

With rapid development of novel nanomaterials (NMs), the state of the art technologies with high efficiency and high-throughput characteristics had been applied for nanosafety evaluation. High-content screening (HCS), a cell-based multi-parametric image analysis technique, was adopted in the evaluation of eight different NMs in this study. A set of different endpoints including reactive oxygen species (ROS) production, Ca2+ transient, mitochondrial membrane potential (MMP) and cellular pH levels were checked in human bronchial epithelial (16HBE) cells after incubating with NMs for 24 hours. All NMs induced significant increase of intracellular ROS levels in 16HBE cells, although the decrease of cell viability was only found in Ag and ZnO NMs-treated cells. MMP level had a dose-response decrease in Ag, ZnO and CeO2 NMs-treated cells, while showed a significant increase in TiO2 NMs-treated cells. All tested NMs showed significant up-regulation of cellular lysosomal pH levels. However, none of NMs caused significant changes in cellular Ca2+ level at 24-hour time point. HCS allows for efficient and reliable screening of multiple responses of cells simultaneously within one screen test, which can avoid the problematic interpretation of investigations when carried on a single toxicological endpoint. Therefore, the present data provide insight and inspiration that HCS is an effective and powerful method for image-based assessments with a broad set of biological endpoints in toxicity evaluation of nanomaterials.