Hour-Level Persistent Multicolor Phosphorescence Enabled by Carbon Dot-Based Nanocomposites Through a Multi-Confinement-Based Approach.

Hour-level persistent room temperature phosphorescence (RTP) phenomena based on multi-confinement carbon dots (CDs) are reported. The CDs-based system reported here (named Si-CDs@B2O3) can be efficiently synthesized by a simple pyrolysis method compared to the established persistent RTP systems. The binding modes of CDs, silica (SiO2), and boron oxide (B2O3) are deduced from a series of characterizations including XRD, FT-IR, and TEM characterization. Further studies show that the formation of covalent bonds between B2O3, SiO2, and CDs play a key role in activating the persistent RTP and preventing its quenching. This is a rare example of a persistent RTP system that exhibits hourly persistent RTP under environmental conditions. Finally, the applications of Si-CDs@B2O3 are demonstrated for anti-counterfeiting, long-duration phosphorescence imaging, and fingerprinting. This synthetic strategy is expected to provide strong technical support for the preparation of persistent RTP CDs and pave the way for the synthesis of persistent RTP CDs in the future.

The Emerging Star of Carbon Luminescent Materials: Exploring the Mysteries of the Nanolight of Carbon Dots for Optoelectronic Applications.

Carbon dots (CDs), a class of carbon-based nanomaterials with dimensions less than 10 nm, have attracted significant interest since their discovery. They possess numerous excellent properties, such as tunability of photoluminescence, environmental friendliness, low cost, and multifunctional applications. Recently, a large number of reviews have emerged that provide overviews of their synthesis, properties, applications, and their composite functionalization. The application of CDs in the field of optoelectronics has also seen unprecedented development due to their excellent optical properties, but reviews of them in this field are relatively rare. With the idea of deepening and broadening the understanding of the applications of CDs in the field of optoelectronics, this review for the first time provides a detailed summary of their applications in the field of luminescent solar concentrators (LSCs), light-emitting diodes (LEDs), solar cells, and photodetectors. In addition, the definition, categories, and synthesis methods of CDs are briefly introduced. It is hoped that this review can bring scholars more and deeper understanding in the field of optoelectronic applications of CDs to further promote the practical applications of CDs.

Hydrophobic Mn-Doped Solid-State Red-Emitting Carbon Nanodots with AIE Effect and Their Hydrogel Composites for Color-Changing Anticounterfeiting.

The aggregation-caused quenching has always limited the high concentration and solid-state applications of carbon nanodots. While the aggregation-induced emission effect, dominated by intramolecular motion, may be an effective means to solve this problem. Here, hydrophobic solid-state red-light carbon nanodots (M-CDs) with 95% yield are synthesized by a one-step hydrothermal method using 2,2'-dithiodibenzoic acid as the carbon source and manganese acetate as the dopant source. The disulfide bond of 2,2'-dithiodibenzoic acid serves as the symmetry center of molecular rotation and Mn catalyzes the synthesis of M-CDs, which promotes the formation of the central graphitic carbon structure. The M-CDs/agar hydrogel composites can achieve fluorescence transition behavior because of the special fluorescence transition properties of M-CDs. When this composite hydrogel is placed in water, water molecules contact with M-CDs through the network structure of the hydrogels, making the aggregated hydrogels of M-CDs fluorescence orange-red under 365 nm excitation. While in dimethyl sulfoxide, water molecules in the hydrogels network are replaced and the M-CDs fluoresce blue when dispersed, providing a potential application in information encryption. In addition, high-performance monochromatic light-emitting diode (LED) devices are prepared by compounding M-CDs with epoxy resin and coating them on 365 nm LED chips.

Design of a Synthetic Strategy to Achieve Enhanced Fluorescent Carbon Dots with Sulfur and Nitrogen Codoping and Its Multifunctional Applications.

Here, a rational strategy to achieve multifunctional N, S codoped carbon dots (N, S-CDs) is reported, aiming to improve the photoluminescence quantum yields (PLQYs) of the CDs. The synthesized N, S-CDs have excellent stability and emission properties independent of excitation wavelength. Through the introduction of S element doping, the fluorescence emission of CDs is red-shifted from 430 to 545 nm, and the corresponding PLQYs can be greatly enhanced from 11.2% to 65.1%. It is found that the doping of S elements causes an increase in the size of CDs and an elevated graphite N content, which may be the key factors to cause the redshift of fluorescence emission. Furthermore, the introduction of S element also serves to suppress the nonradiative transitions, which may be responsible for the elevated PLQYs. Besides, the synthesized N, S-CDs have certain solvent effect and can be applied to detect water content in organic solvents, and have strong sensitivity to alkaline environment. More importantly, the N, S-CDs can be used to achieve an "on-off-on" dual detection mode between Zr4+ and NO2 - . In addition, N, S-CDs combinedwith polyvinylpyrrolidone (PVP) can also be utilized as fluorescent inks for anti-counterfeiting applications.

The Emerging Development of Multicolor Carbon Dots.

As a relatively new type of fluorescent carbon-based nanomaterials, multicolor carbon dots (MCDs) have attracted much attention because of their excellent biocompatibility, tunable photoluminescence (PL), high quantum yield, and unique electronic and physicochemical properties. The multicolor emission characteristics of carbon dots (CDs) obviously depend on the carbon source precursor, reaction conditions, and reaction environment, which directly or indirectly determines the multicolor emission characteristics of CDs. Therefore, this review is the first systematic classification and summary of multiple regulation methods of synthetic MCDs and reviews the recent research progress in the synthesis of MCDs from a variety of precursor materials such as aromatic molecules, small organic molecules, and natural biomass, focusing on how different regulation methods produce corresponding MCDs. This review also introduces the innovative applications of MCDs in the fields of biological imaging, light-emitting diodes (LEDs), sensing, and anti-counterfeiting due to their excellent PL properties. It is hoped that by selecting appropriate adjustment methods, this review can inspire and guide the future research on the design of tailored MCDs, and provide corresponding help for the development of multifunctional MCDs.

Promising Fast Energy Transfer System Between Graphene Quantum Dots and the Application in Fluorescent Bioimaging.

Tunable photoluminescence performance of graphene quantum dots (GQDs) is one of the most important topics for the development of GQDs. In this paper, we report lattice-doped GQDs (boron-doped GQDs (B-GQDs) and phosphorus-doped GQDs (P-GQDs)). Because of the matched band structure, the fast energy transfer between blue-emitted B-GQDs (emission wavelength: 460 nm) and orange-emitted P-GQDs (emission wavelength: 630 nm) can induce an efficient fluorescence emission in P-GQDs once B-GQDs are excited under the optimal excitation wavelength of 460 nm. Moreover, with the effective energy transfer, the quantum yield of P-GQDs increased to 0.48, which is much higher than that of pure P-GQDs. We also demonstrated the potentials of this system for fluorescent bioimaging in vitro.

[Association between Severity of Scrub Typhus and Serum Procalcitonin Level].

Objective To explore the association between the severity of scrub typhus (ST) and the serum procalcitonin (PCT) level. Methods The clinical data of 58 ST patients who were treated in the First Affiliated Hospital of Xiamen University and confirmed by Xiamen Municipal Center for Disease Prevention and Control (CDC) from January 2016 to October 2017,were retrospectively analyzed. According to clinical manifestations and related laboratory tests,these patients were divided into four grades:Ⅰ,Ⅱ,Ⅲ,and Ⅳ. These four grade groups were compared in terms of age,interval from symptom onset to hospital presentation,hospitalization days,and serum PCT level. Results These 58 patients were divided into four grade groups:grade Ⅰ group (n=17),grade Ⅱ group (n=17),grade Ⅲ group (n=11),and grade Ⅳ group (n=13). No significant difference was found among these four groups in terms of age (F=0.618,P=0.606),interval from symptom onset to hospital presentation (F=1.744,P=0.169),and hospitalization days (F=0.398,P=0.755).However,the median serum PCT level in the grade Ⅳ patients[2.60(1.33,61.08)ng/ml] was significantly higher than those in grade I[0.24(0.10,0.33)ng/ml;Z=-4.63,P=0.000], grade Ⅱ[0.29(0.21,0.51)ng/ml;Z=-4.63,P=0.000], and grade Ⅲ[1.33(0.89,2.41)ng/ml;Z=-2.09,P=0.040].The median serum PCT level in the grade Ⅲ patients was also significantly higher than grade Ⅰ (Z=-4.16,P=0.000)and grade Ⅱ(Z=-3.83,P=0.000).There was no significant difference between the grade Ⅰ patients and grade Ⅱ patients(Z=-1.37,P=0.170).There was significantly positive correlation between PCT level and the severity of ST (r=0.804,P=0.000).Conclusion There is positive correlation between serum PCT level and the severity of ST,and serum PCT level may be a biomarker in assessing the severity of ST.

Interleukin-22 exacerbates airway inflammation induced by short-term exposure to cigarette smoke in mice.

AIM: Interleukin-22 (IL-22) exhibits both proinflammatory and anti-inflammatory properties in various biological processes. In this study we explored the effects of exogenous recombinant IL-22 (rIL-22) on cigarette smoke (CS)-induced airway inflammation in mice. METHODS: Male C57BL/6 mice were divided into groups: (1) CS group exposed to tobacco smoke for 3 consecutive days, (2) rIL-22 group received rIL-22 (100 mg/kg, ip), and (3) CS plus rIL-22 group, received rIL-22 (100 mg/kg, ip) before the CS exposure. The airway resistance (Rn), lung morphology, inflammatory cells in the airways, and inflammatory cytokines and CXCR3 ligands in both bronchoalveolar lavage (BAL) fluids and lung tissues were analyzed. RESULTS: CS alone significantly elevated IL-22 level in the BAL fluid. Both CS and rIL-22 significantly augmented airway resistance, an influx of inflammatory cells into the airways and lung parenchyma, and significantly elevated levels of pro-inflammatory cytokines (TGFß1 and IL-17A) and CXCR3 chemokines (particularly CXCL10) at the mRNA and/or protein levels. Furthermore, the effects of rIL-22 on airway resistance and inflammation were synergistic with those of CS, as demonstrated by a further increased Rn value, infiltration of greater numbers of inflammatory cells into the lung, higher levels of inflammatory cytokines and chemokines, and more severe pathological changes in CS plus rIL-22 group as compared to those in CS group. CONCLUSION: Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands.

[Clinical evaluation of 136 inpatients with bronchiectasis in Peking Union Medical College Hospital].

OBJECTIVE: To summarize the clinical features of bronchiectasis. METHODS: We retrospectively analyzed the clinical data of 136 patients who had been admitted to Peking Union Medical College Hospital from January 2010 to December 2012 due to bronchiectasis, which was confirmed by high-resolution computed tomography. RESULTS: The average age of these 136 patients (61 men and 75 women) was (57.7±16.3) years. The average clinical history was (17.2±15.8) years. The exact etiology was unidentified in 77.2% (105/136) of the patients. The most commonly identified cause was previous infections (14.7%, 20/136), particularly tuberculosis. The main symptoms of bronchiectasis were cough and sputum production. The types of bronchiectasis were cylindrical in 37.7% (37/98), varicose in 40.8% (40/98), cystic in 21.4% (21/98) of these patients. Multilober involvement was most common (77.2%, 105/136). The most commonly involved lobes were left lower lobe (76.5%, 104/136). Of 77 patients who had undergone pulmonary function test, 47 (61.0%) showed obstructive. For each bronchiectasis type, the values (percentages of predicted) of forced expiratory volume in one second (FEV1) (P=0.918), forced vital capacity (FVC) (P=0.982), and FEV1/FVC (P=0.211) showed no statistical significance. The most commonly identified pathogen in sputum culture was Pseudomonas aeruginosa, which was sensitive to most broad-spectrum antibiotics. Current infections were most common in patients with cystic bronchiectasis, among whom rales were frequently heard. CONCLUSIONS: Most bronchiectasis patients are old women. The main etiology is previous infection, especially tuberculosis. The main symptom of bronchiectasis is productive cough. Many patients can have obstructive pulmonary function. The distribution of lesions is diffuse, and the lesions are often seen in both lungs, particularly in the left lower lobe. Cystic bronchiectasis may be a more severe type, and should be carefully managed once identified by radiology.

Differential expression of the inflammation-associated chemokines/cytokines in mouse lung after exposure to cigarette smoke and smoking cessation.

OBJECTIVE: To determine the changes in the airway inflammation-related cytokine/chemokine profiles after exposure to cigarette smoke (CS) and smoking cessation (SC). METHODS: A total of 18 male C57BL/6 mice were equally divided into three groups: CS group, SC group, and normal control group. The airway resistance, lung morphology, and collagen deposition around airways were determined. HE staining and Masson trichrome staining were used for histopathological analysis. The inflammatory cells in bronchoalveolar lavage fluid (BALF) were assessed. The inflammation-associated cytokines were determined using real-time PCR and immunohistochemistry. Expressions of CXCR3 ligands including the CXCL9, CXCL10, CXCL11 and other cytokines in lung tissue and BALF were also analyzed. RESULTS: The airway resistance significantly increased in both CS group and SC group when compared with the normal control group. Lung pathological scores in both CS group and SC group were also higher than that in the normal control group, while there was no significant difference between the CS group and SC group. Inflammatory cells including the neutrophils, macrophages, and lymphocytes also increased in both the CS group and SC group at both mRNA and protein levels. The mRNA levels of CXCL9, CXCL10, MMP9, and MMP12 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). The protein expression levels of CXCL9, CXCL10, CXCL11, MMP2, MMP9, MMP12, and TGF-Β1 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). Compared with the normal control group,the concentrations of CXCL9, CXCL10, CXCL11, IL-8, and TGF-Β1 in the BALF supernatants of the CS group and SC group significantly increased (P<0.05); in addition, the IL-6 and TNF-Α concentrations also increased in the CS group (both P<0.05). CONCLUSIONS: CS exposure triggers inflammatory cell flux and accumulation in the lung parenchyma and BALF. As a consequence, the inflammatory cytokines increase dramatically. After CS, the cytokines/chemokines can decrease, but is still higher than in non-smokers.

Evolution and fabrication of carbon dot-based room temperature phosphorescence materials.

Traditional room temperature phosphorescence (RTP) materials usually include organometallic composites and pure organic compounds, which generally possess the disadvantages of high toxicity, high cost and complicated preparation. Carbon dots (CDs) are a new kind of luminescent material and have attracted widespread attention due to their benefits of excellent tunable emission, nice biocompatibility, cost-effectiveness, facile preparation and environmental friendliness. Since photoluminescence is an important luminescent property of carbon-based fluorescent nanomaterials, CD-based RTP materials have sparked a new research wave due to the properties of extremely long phosphorescence lifetime, large Stokes shift and high environmental sensitivity. In order to construct excellent CD-based RTP materials, many attempts have been made, and the corresponding progress has been achieved. Herein, we summarize the progress in CD-based RTP materials in recent years, mainly focusing on the outstanding contributions over the years, phosphorescence emission, phosphorescence lifetime, preparation and application of CD-based RTP materials. In particular, this review provides a comprehensive summary and analyze the outstanding contributions in the fields of the phosphorescence emission and phosphorescence lifetime of CD-based RTP materials over the years. Finally, several existing challenges and the future outlook of RTP materials based on CDs have been put forward.

Unveiling Unconventional Luminescence Behavior of Multicolor Carbon Dots Derived from Phenylenediamine.

Fluorescence regulation of carbon dots (CDs) during their preparation has become a hot research topic. In this work, multicolor fluorescent CDs with unconventional luminescence behavior are prepared by using o-, m-, or p-phenylenediamine (o-PD, m-PD, or p-PD, respectively) and 2,3-dihydroxynaphthalene with rich hydroxyl groups as reaction precursors. Tunable multicolor fluorescent CDs with bright blue, yellow, and red colors can be obtained by a solvothermal method under the joint action of ethanol and hydrochloric acid. The fluorescence emission of the synthesized CDs follows a rule of o-PD to m-PD to p-PD from blue to red, which is contrary to most previously reported results (the luminescence from blue to red following an order of m-PD to o-PD to p-PD). Our results reveal that the differences in the polymerization, surface states, functional groups, and graphite N content of CDs might be the main reasons for the unconventional luminescence behavior. In addition, these multicolor CDs have good applications in the fields of light-emitting diode lighting and anticounterfeiting.

Boosting efficiency of luminescent solar concentrators using ultra-bright carbon dots with large Stokes shift.

Luminescent solar concentrators (LSCs) are able to collect sunlight from a large-area to generate electric power with a low cost, showing great potential in building-integrated photovoltaics. However, the low efficiency of large-area LSCs caused by the reabsorption losses is a critical issue that hampers their practical applications. In this work, we synthesized novel yellow emissive carbon dots (CDs) with a large Stokes shift of 193 nm, which exhibit nearly zero reabsorption. The quantum yield (QY) of the yellow emitting CDs is up to 61%. The yellow emitting CDs can be employed to fabricate high-performance large-area LSCs due to successful suppression of the reabsorption losses. The as-prepared LSCs are able to absorb 14% of the sunlight as the absorption of the CDs matches well with the sun's spectrum. The large-area LSC (10 × 10 cm2) with a laminated structure based on the yellow emitting CDs achieves an optical conversion efficiency (ηopt) of 4.56% and power conversion efficiency (ηPCE) of 4.1% under natural sunlight (45 mW cm-2), which are significantly higher than other previously reported works with similar sizes. Furthermore, the prepared high-performance LSCs show good stability. This method of synthesizing novel CDs for high-efficiency LSCs provides a useful platform for future study and practical application of LSCs.

Platycodon D-induced A549 Cell Apoptosis through RRM1-Regulated p53/VEGF/ MMP2 Pathway.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related deaths worldwide. Platycodin D (PD), a major pharmacological constituent from the Chinese medicinal herb named Platycodonis Radix, has shown potent anti-tumor activity. Also, it is reported that PD could inhibit cellular growth in the non-small-cell lung carcinoma (NSCLC) A549 cell line. However, the underlying mechanism is not fully clarified. METHODS: Cell proliferation was measured by MTT assay. Annexin V and propidium iodide (PI) assay were employed to study the apoptosis effects of PD on A549 cells. Western blot analysis was used to evaluate protein expression. Also, we used a siRNA against p53, as well as a plasmid-based RRM1 over-expression to investigate their functions. RESULTS: It is demonstrated that PD inhibited A549 cell proliferation in a dose- and time-dependent manner. Further investigations showed that PD induced cell apoptosis, which was supported by dose-dependent and time-dependent caspase-3 activation and p53/VEGF/MMP2 pathway regulation. Also, PD demonstrated the inhibition effect of ribonucleotide reductase M1 (RRM1), whose role in various tumors is contradictory. Remarkably, in this work, RRM1 overexpression in A549 cells could have a negative impact on the regulation of the p53/VEGF/MMP2 pathway induced by PD treatment. Note that RRM1 overexpression also attenuated cell apoptosis and inhibition of cell proliferation of A549 treated with PD. CONCLUSION: The results suggested that PD could inhibit A549 cell proliferation and induce cell apoptosis by regulating p53/VEGF/MMP2 pathway, in which RRM1 plays an important role directly.

Dual-emission carbon dots for sensitive fluorescence detection of metal ions and ethanol in water.

Carbon dots (CDs) have been widely used in biomedical fields because of their superior optical properties, high sensitivity and high selectivity to specific substances. However, there are few studies on trace detection of the ethanol content in aqueous solution using CDs. Herein, novel red fluorescent CDs with dual emission are synthesized and show good dispersibility in various solvents and excitation independence of photoluminescence (PL). After investigating the structure and properties of the red CDs, a multifunctional fluorescent nanoprobe based on the red CDs with high-sensitivity detection for dual-ion trace detection of Fe3+ and Cu2+ can be successfully constructed. The limit of detection of Fe3+ and Cu2+ can be up to 0.024 µM and 0.036 µM, respectively, which is superior to that in previous reports. Meanwhile, in view of the specific solvent effect on their PL, the red CDs are able to be applied for trace detection of the ethanol content in aqueous solution. The methods of colorimetry and fluorescence spectrometry are utilized to perform the threshold test and high-sensitivity quantitative analysis of the ethanol content in aqueous solution. Based on this, a multifunctional fluorescent nanoprobe based on the dual-emission red CDs can be obtained, which provides a promising way for their applications in detection and sensing fields.

Benchmarking of 5 algorithms for high-resolution genotyping of human leukocyte antigen class I genes from blood and tissue samples.

Background: Specific alterations in human leukocyte antigen class I (HLA-I) loci are associated with clinical outcomes for immune checkpoint inhibitors, which increase the clinical relevance of accurate high-resolution HLA genotyping in immuno-oncology applications. Numerous algorithms have been developed for high- to full-resolution HLA genotyping by next-generation sequencing (NGS) data; however, Sanger sequencing-based typing (SBT) remains the gold standard. With the increasing use of NGS for clinical oncology, it is important to identify the computational tool with comparable performance as the gold standard. This study aimed to benchmark 5 algorithms against SBT for the high-resolution typing of classical HLA-I genes for targeted NGS data from blood and tissue samples. Methods: Paired white blood cell (WBC), plasma, and tissue deoxyribonucleic acid (DNA) samples derived from 22 cancer patients with known HLA genotypes were sequenced using a panel of all the following exons of classical HLA-I genes: HLA-A, HLA-B, and HLA-C. NGS-based genotypes were generated by the 5 different algorithms, including HLA-HD, HLAscan, OptiType, Polysolver, and xHLA. Accuracy was defined as the concordance between the SBT and NGS-based algorithms. Accuracy was computed as the fraction of all the alleles with concordant genotype using the SBT and any of the algorithm over the total number of alleles. Results: In relation to the WBC, plasma, and tissue samples, all 5 algorithms were highly accurate at low-resolution HLA-I genotyping, but had more varied accuracy at high-resolution HLA-I genotyping, particularly in HLA-A. The in-silico analyses revealed that high-resolution genotyping by all 5 algorithms achieved approximately 90% accuracy at sequencing depths of 6,000× - 100× for the WBC samples, at 6,000× - 700× for the plasma samples, and at 1,000× - 100× for the tissue samples. Among the 5 algorithms, HLA-HD was consistently accurate at high-resolution HLA-I genotyping, and had an accuracy of 93.9% for the WBC samples, 87.9% for the plasma samples, and 94.2% for tissue samples even at a 50× sequencing depth. Conclusions: We found that HLA-HD was an accurate algorithm for the high-resolution genotyping of classical HLA-I genes sequenced by our targeted panel, particularly at a sequencing depth ≥300× for blood and tissue samples.

Red and yellow emissive carbon dots integrated tandem luminescent solar concentrators with significantly improved efficiency.

Luminescent solar concentrators (LSCs) can collect solar light from a large area and concentrate it on their small-area edges mounted with solar cells for efficient solar-to-electricity conversion. Thus, LSCs show huge promise for realizing building-integrated photovoltaics because of their semi-transparency and light weight. However, the low optical efficiency of LSCs becomes a great obstacle for their application in real energy conversion. Herein, yellow emissive carbon dots with a record-breaking ultrahigh quantum yield of up to 86.4% were prepared via a simple hydrothermal approach using low-cost precursors. By combining them with red emissive carbon dots (quantum yield of 17.6%), a large area (∼100 cm2) tandem LSC was fabricated. The power conversion efficiency (PCE) of the large-area carbon dot-integrated tandem LSC reaches up to 3.8%, which is among the best reported in literature for a similar lateral size of LSCs. In particular, the tandem structure based on two laminated layers is novel, and is fit for the real structural application of keeping windows warm, where two glass slides are usually used. The high-efficiency tandem LSC using eco-friendly carbon dots as fluorophores paves way for real applications of LSCs.

Torin2 inhibits the EGFR-TKI resistant Non-Small Lung Cancer cell proliferation through negative feedback regulation of Akt/mTOR signaling.

It is known that mammalian target of rapamycin (mTOR) signaling plays an important role in NSCLC cells proliferation. Torin2 is a second-generation ATP-competitive inhibitor which is selective for mTOR activity. In this study, we investigated whether torin2 was effective against lung cancer cells, especially EGFR-TKIs resistant NSCLC cells. We found that torin2 dramatically inhibited EGFR-TKI resistant cells viability in vitro. In xenograft model, torin2 treatment significantly reduced the volume and weight of xenograft tumor in the erlotinib resistant PC9/E cells. Additionally, autophagy protein of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3II/I (LC3II/I) increased in PC9/E after torin2 treatment. Torin2 blocked the level of phosphorylated S6 and the phosphorylation of Akt at both T308 and S473 sites compared with erlotinib treatment. Furthermore, TUNEL assay showed that apoptosis of tumor tissue increased significantly in the torin2 treatment group. Immunohistochemical analysis demonstrated that tumor angiogenesis was obviously inhibited by torin2 treatment in EGFR-TKI resistant group. Collectively, our results suggested that torin2 could inhibit the NSCLC cells proliferation by negative feedback regulation of Akt/mTOR signaling and inducing autophagy. This suggests that torin2 could be a novel therapeutic approach for EGFR-TKI resistant NSCLC.

Distinct antibacterial activity of a vertically aligned graphene coating against Gram-positive and Gram-negative bacteria.

Graphene-based nanomaterials (GBNs) are known to exhibit biocidal activities, however, the combined effect of GBNs based on physical disruption and oxidative stress on different types of bacteria remain unclear. Here, we use both Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) bacteria to investigate the antimicrobial properties of vertically and horizontally aligned graphenes grown on semiconductor silicon (Si) and insulator silicon dioxide (SiO2). It is found that the bacteria show different sensitivity to isomeric-structured GBNs. Gram-negative bacteria are more vulnerable to graphene-coated Si substrates than to SiO2, because the less negatively charged membrane enhances the electron transfer effect that extracts the electrons from the microbial membranes, and Gram-positive bacteria seem to show more susceptibility to physical puncturing of vertically aligned graphene than to horizontally aligned graphene due to the nature of the compound and the shape of the membrane structure. Subsequently, the vertically aligned graphene Si substrate (G@V-Si) exerts the superior antimicrobial ability on all the bacteria. Finally, all the above GBNs show low cytotoxicity and high biocompatibility, and the robust in vivo antibacterial effect indicates that G@V-Si could serve as an ideal platform for antimicrobial treatment.

Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers.

Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. Methods: By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers. The discovery cohort included 5 COPD patients under acute exacerbation (AECOPD) and 5 age- and gender-matched non-COPD smokers. One putative candidate autoantibody, anti-lactoferrin IgG, was further investigated by using immunoblotting with a large validation cohort containing 124 healthy controls, 92 patients with AECOPD and 52 patients with stable COPD. Results: We show that i) autoantigens targeted by autoantibodies with higher titers in COPD patients were enriched in extracellular regions, while those with lower titers in COPD patients were enriched in intracellular compartments. ii) levels of IgG autoantibodies against many neutrophil granule proteins were significantly higher in COPD patients than in non-COPD smokers. Furthermore, increased levels of anti-lactoferrin antibodies in COPD patients were confirmed in a cohort with a large number of samples. Conclusion: The comprehensive autoantibody profiles from COPD patients established in this study demonstrated for the first time a shift in the cellular localization of antigens targeted by autoantibodies in COPD.