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Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm -1 (0.36 THz) on monolayer MoSe 2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe 2 . The generality of the RBM in nanoscale curved monolayer WSe 2 and bilayer MoSe 2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe 2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale., (© 2024 Wiley‐VCH GmbH.)

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Aim: To quantify the performance of artificial intelligence (AI) in detecting glaucoma with spectral-domain optical coherence tomography (SD-OCT) images., Methods: Electronic databases including PubMed, Embase, Scopus, ScienceDirect, ProQuest and Cochrane Library were searched before May 31, 2023 which adopted AI for glaucoma detection with SD-OCT images. All pieces of the literature were screened and extracted by two investigators. Meta-analysis, Meta-regression, subgroup, and publication of bias were conducted by Stata16.0. The risk of bias assessment was performed in Revman5.4 using the QUADAS-2 tool., Results: Twenty studies and 51 models were selected for systematic review and Meta-analysis. The pooled sensitivity and specificity were 0.91 (95%CI: 0.86-0.94, I 2 =94.67%), 0.90 (95%CI: 0.87-0.92, I 2 =89.24%). The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 8.79 (95%CI: 6.93-11.15, I 2 =89.31%) and 0.11 (95%CI: 0.07-0.16, I 2 =95.25%). The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 83.58 (95%CI: 47.15-148.15, I 2 =100%) and 0.95 (95%CI: 0.93-0.97). There was no threshold effect (Spearman correlation coefficient=0.22, P >0.05)., Conclusion: There is a high accuracy for the detection of glaucoma with AI with SD-OCT images. The application of AI-based algorithms allows together with "doctor+artificial intelligence" to improve the diagnosis of glaucoma., Competing Interests: Conflicts of Interest: Shi NN, None; Li J, None; Liu GH, None; Cao MF, None., (International Journal of Ophthalmology Press.)

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease., Competing Interests: Declaration of Competing Interest Shi-Qi Xiao and Tian-Zi Wen performed most of the experiments. Shi-Qi Xiao and Xiao-Hong Yao wrote the manuscript. Zhuang Li, Yan Wang and Mian-Fu Cao performed the data analyses. Zhi-Cheng He, Tao Luo, Jia Ge, Rui Tang, Wen-Juan Fu, Hai-Tao Guo and Yan-Xia Wang collected the clinical information and autopsy cases. Lu Chen, Qin Niu, Shuai Wang, Yang Lan and Qing-Rui Li prepared the reagents and performed the immunohistochemical staining. Yi-Fang Ping performed data analyses. Hong Shen, Xin-Yu Chen and He-Yuan Chen collected information. Xiao-Hong Yao, Yan-Qing Ding and Xiu-Wu Bian designed the study, revised the manuscript, and provided administrative management. All authors read and approved the submitted version., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Investigation of proteins in their native state is the core of proteomics towards better understanding of their structures and functions. Surface-enhanced Raman spectroscopy (SERS) has shown its unique advantages in protein characterization with fingerprint information and high sensitivity, which makes it a promising tool for proteomics. It is still challenging to obtain SERS spectra of proteins in the native state and evaluate the native degree. Here, we constructed 3D physiological hotspots for a label-free dynamic SERS characterization of a native protein with iodide-modified 140 nm Au nanoparticles. We further introduced the correlation coefficient to quantitatively evaluate the variation of the native degree, whose quantitative nature allows us to explicitly investigate the Hofmeister effect on the protein structure. We realized the classification of a protein of SARS-CoV-2 variants in 15 min, which has not been achieved before. This study offers an effective tool for tracking the dynamic structure of proteins and biomedical research., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland., (© 2022 The Pathological Society of Great Britain and Ireland.)

Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temozolomide response of gliomas. However, whether inducing ferroptosis could affect invasive growth of glioblastoma cells and which ferroptosis-related regulators were involved in temozolomide resistance are still unclear. In this study, we treated glioblastoma cells with RSL3, a ferroptosis inducer, in vitro (cell lines) and in vivo (subcutaneous and orthotopic animal models). The treated glioblastoma cells with wild-type or mutant IDH1 were subjected to RNA sequencing for transcriptomic profiling. We then analyze data from our RNA sequencing and public TCGA glioma database to identify ferroptosis-related biomarkers for prediction of prognosis and temozolomide resistance in gliomas. Analysis of transcriptome data from RSL3-treated glioblastoma cells suggested that RSL3 could inhibit glioblastoma cell growth and suppress expression of genes involved in cell cycle. RSL3 effectively reduced mobility of glioblastoma cells through downregulation of critical genes involved in epithelial-mesenchymal transition. Moreover, RSL3 in combination with temozolomide showed suppressive efficacy on glioblastoma cell growth, providing a promising therapeutic strategy for glioblastoma treatment. Although temozolomide attenuated invasion of glioblastoma cells with mutant IDH1 more than those with wild-type IDH1, the combination of RSL3 and temozolomide similarly impaired invasive ability of glioblastoma cells in spite of IDH1 status. Finally, we noticed that both ferritin heavy chain 1 and ferritin light chain predicted unfavorable prognosis of glioma patients and were significantly correlated with mRNA levels of methylguanine methyltransferase as well as temozolomide resistance. Altogether, our study provided rationale for combination of RSL3 with temozolomide to suppress glioblastoma cells and revealed ferritin heavy chain 1 and ferritin light chain as biomarkers to predict prognosis and temozolomide resistance of glioma patients., (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

Although the tumorigenic potential of glioma stem cells (GSCs) is associated with multiple molecular alterations, the gene amplification status of GSCs has not been elucidated. Overexpression of HomeoboxA5 (HOXA5) is associated with increased glioma malignancy. In this study, we identify the gene amplification and protein overexpression of HOXA5 in GSCs and its function in regulating GSC maintenance and the downstream transcriptional effector, to explore the significance of HOXA5 amplification/overexpression for GSC identification and prognostic determination. The HOXA5 gene is significantly amplified in glioblastoma (GBM) and is an independent prognostic factor for predicting worse patient outcomes. Specifically, HOXA5 gene amplification and the resultant protein overexpression are correlated with increased proportions of GSCs and enhanced self-renewal/invasiveness of these cells. Disruption of HOXA5 expression impairs GSC survival and GBM tumor propagation. Mechanistically, HOXA5 directly binds to the promoter region of protein tyrosine phosphatase receptor type Z1 (PTPRZ1), thereby upregulating this gene for GSC maintenance. Suppression of PTPRZ1 largely compromises the pro-tumoral effect of HOXA5 on GSCs. In summary, HOXA5 amplification serves as a genetic biomarker for predicting worse GBM outcome, by enhancing PTPRZ1-mediated GSC survival., (Copyright © 2022. Published by Elsevier B.V.)

Defects can locally tailor the electronic properties of 2D materials, including the band gap and electron density, and possess the merit for optical and electronic applications. However, it is still a great challenge to realize rational defect engineering, which requires quantitative study of the effect of defects on electronic properties under ambient conditions. In this work, we employed tip-enhanced photoluminescence (TEPL) spectroscopy to obtain the PL spectra of different defects (wrinkle and edge) in mechanically exfoliated thin-layer transition metal dichalcogenides (TMDCs) with nanometer spatial resolution. We quantitatively obtained the band gap and electron density at defects by analyzing the wavelength and intensity ratio of excitons and trions. We further visualized the strain distribution across a wrinkle and the edge-induced reconstructive regions of the band gap and electron density by TEPL line scans. The doping effect on the Fermi level and optical performance was unveiled through comparative studies of edges on TMDC monolayers of different doping types. These quantitative results are vital to guide defect engineering and design and fabrication of TMDC-based optoelectronics devices.

We combined a microporous polymer backbone with an organic redox-active dopant to construct a reversible electrode system based on the conversion-(de)incorporation behaviour of the dopant. The correspondence between the reversible conversion-(de)incorporation mechanism of the dopant and the electrochemical performance of the designed electrode system was established by electrochemical quartz crystal microbalance and in situ Fourier transform infrared spectroscopy.

Glioma cells with stem cell-like properties are crucial for tumor initiation, progression and therapeutic resistance. Therefore, identifying specific factors in regulating stem-like traits is critical for the design of novel glioma therapeutics. Herein, we reported that ADP-Ribosylation Factor Like GTPase 4C (ARL4C) was highly expressed in glioma stem-like cells (GSLCs). GSLCs, determined by the efficiency of sphere formation in vitro and tumor growth in vivo , was increased by overexpression of ARL4C. ARL4C induced the tumorigenesis through ALDH1A3. Analyses of 325 patient specimens showed that ARL4C was highly expressed in glioblastoma (GBM) as compared with lower grade gliomas. In addition, higher level ARL4C expression in glioma was correlated with poorer progression-free survival and overall survival of patients. Therefore, ARL4C may act as a novel prognostic marker and a therapeutic target for GBM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Electrochemical tip-enhanced Raman spectroscopy (EC-TERS) is a powerful technique for the in situ study of the physiochemical properties of the electrochemical solid/liquid interface at the nanoscale and molecular level. To further broaden the potential window of EC-TERS while extending its application to opaque samples, here, we develop a top-illumination atomic force microscopy (AFM) based EC-TERStechnique by using a water-immersion objective of a high numerical aperture to introduce the excitation laser and collect the signal. This technique not only extends the application of EC-TERS but also has a high detection sensitivity and experimental efficiency. We coat a SiO 2 protection layer over the AFM-TERS tip to improve both the mechanical and chemical stability of the tip in a liquid TERS experiment. We investigate the influence of liquid on the tip-sample distance to obtain the highest TERS enhancement. We further evaluate the reliability of the as-developed EC-AFM-TERS technique by studying the electrochemical redox reaction of polyaniline. The top-illumination EC-AFM-TERS is promising for broadening the application of EC-TERS to more practical systems, including energy storage and (photo)electrocatalysis.

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.

Immunotherapies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) axis have been emerging as a promising therapeutic strategy to treat lung cancer. PD-1 is preferentially expressed by activated T lymphocytes; but whether/how its expression by tumor-associated macrophages (TAMs) in lung adenocarcinoma remains elusive. Herein, we investigate the frequency of PD-1 expression on TAMs in mouse allografts by flow cytometry analysis and evaluate the spatial distribution and clinicopathological significance of PD-1 + TAMs in 213 cases of human lung adenocarcinoma specimens by immunohistochemical staining. We find the expression of PD-1 by both mouse and human TAMs. Mouse PD-1 + TAMs possess unique transcriptional profile as compared to PD-1 - TAMs. Furthermore, PD-1 is preferentially expressed by CD163 + TAMs in the tumor stroma than those in the tumor islets of lung adenocarcinoma. Stromal PD-1 + TAM infiltration is an independent predictor of reduced survival as determined by univariate (P < .001) and multivariate (P = .023) analysis. Moreover, patients with high stromal PD-1 + TAMs but low tumor cell PD-L1 expression have the shortest survival (P = .0001). Our study demonstrates that PD-1 + TAMs have unique gene expression characteristics and PD-1 + TAMs in the tumor stroma is a potential prognostic factor in lung adenocarcinoma, suggesting that a better understanding of PD-1 + TAMs will be beneficial for immunotherapy of lung adenocarcinoma patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD-L1 high /TIL high ; TMIT II, PD-L1 low /TIL low ; TMIT III, PD-L1 high /TIL low ; and TMIT IV, PD-L1 low /TIL high ) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC)., Methods and Results: Immunohistochemistry (IHC) was applied to evaluate the expression of PD-L1 and the spatial distribution of programmed cell death 1 (PD-1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD-1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma. The density of TILs was a poor prognostic factor in LAC but a favorable one in SCC. PD-L1 levels and its clinical prognostic significance differed in LAC vs SCC. LAC patients with TMIT III and SCC patients with TMIT I had the longest survival, respectively (P = .0197 and .0049). Moreover, TMIT stratification based on tumor cell PD-L1 expression and stromal CD8 + TILs could be considered as an independent prognostic factor of SCC patients' survival as determined by both univariate and multivariate analysis., Conclusion: Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of LAC and SCC patients and highlights the importance of the integrative assessment of PD-L1 status and TILs' spatial distribution to predict patients' prognosis., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Leucine aminopeptidase (LAP), an important proteolytic enzyme, is closely associated with diverse physiological and pathological disorders such as liver injury and cancers. Hence, it is imperative to develop an effective method to detect LAP activity for early diagnosis of diseases. In this work, we report a novel SERS probe bis-s-s'-[(s)-2-amino-N-(3-thiophenyl)-Leu]. (b-(s)-ANT-Leu) with an l-leucine amide group, which can specially respond to LAP, to assay the LAP activity according to the SERS spectral changes between the probe molecule and its corresponding hydrolysis product resulting from the catalysis of LAP. This SERS approach features high selectivity on account of the specificity of the reaction combined with the instinctive fingerprinting ability of SERS and shows a good linear relationship in a wide range from 0.2 to 100 mU mL -1 with a detection limit as low as 0.16 mU mL -1 . In addition, the SERS-based strategy can be competent for LAP activity detection in clinical patient serum samples and LAP inhibitor evaluation, demonstrating its great potential in the pathological analysis for diseases involving LAP and the screening of LAP inhibitors.

Hybrid formation is a fundamental process in normal development and tissue homeostasis, while the presence and the biological role of hybrids between tumor-associated macrophages (TAMs) and glioblastoma (GBM) cells remain elusive. In this study, we observed that TAM-GBM cell hybrids existed in human GBM specimens as demonstrated by co-expression of glioma biomarkers (GFAP, IDH1 R132H and PDGFRA) and macrophage biomarkers (CD68 and CD14). Furthermore, TAM-GBM cell hybrids could also be found in C57BL/6 mice orthotopically inoculated with mouse GBM cells labeled with RFP and after co-culture of bone marrow-derived macrophages from GFP-expressed mice with RFP-labeled GBM cells. The hybrids underwent nuclear reprogramming with unique gene expression profile as compared to parental cells. Moreover, glioma invasion-associated genes were enriched in the hybrids that possessed higher invasiveness, and more hybrids in the invasive margin of GBM were observed as compared to GBM core area. Our data demonstrate the presence of TAM-GBM cell hybrids that enhance GBM invasion. With a better understanding of TAM-GBM cell hybrids, new therapeutic strategies targeting GBM will be developed to treat GBM patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN-PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b + /CD163 + TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN-PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN-PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential.

Objective: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis., Methods: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels., Results: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001)., Conclusion: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases., Abbreviations: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.

The association between diabetes and inflammatory periodontal diseases has been studied extensively. However, there is a lack of robustness and homogeneity among studies describing effects of periodontal treatment on glycemic control. The aim of this study was to carry out a meta-analysis to understand whether periodontal treatment could improve glycemic control in type 2 diabetic patients. Electronic searches were carried out on MEDLINE, EMBASE and the Cochrane central register of controlled trials from 1980 to July 2012. Randomized controlled trials of periodontal therapy on glycemic control in diabetic patients with a minimum of 3 months of follow-up were included. Meta-analysis was carried out with 8 studies involving 515 participants using Stata 11.0 software. Our results showed that periodontal treatment could lead to a significant decrease in HbA1c level. The standardized mean difference between intervention groups and control groups was significant: 1.03% (95% confidence interval: 0.31% to 1.70%, P = 0.003) from baseline to 3 months, and 1.18% (95% confidence interval: 0.72% to 1.64%, P < 0.001) from baseline to 6 months. Periodontal treatment could lead to a non-significant decrease in fasting plasma glucose (FPG) levels from baseline to 3 months. The standardized mean difference between the intervention and the control group was 0.69 mg/dl (95% confidence interval: -0.27 mg/dl to 1.66 mg/dl, P = 0.158). Our analysis indicated that periodontal treatment could improve glycemic control in type 2 diabetic patients with periodontal diseases.

Aim: Chemerin is a new adipokine involved in adipogenesis and insulin resistance. Since ethanol affects the insulin sensitivity that is closely associated with adipokines. The aim of this study was to investigate the effects of ethanol on chemerin in humans and rats., Methods: In the human study, 148 men who consumed alcohol for more than 3 years and 55 men who abstained from alcohol were included. Based on ethanol consumption per day, the drinkers were classified into 3 groups: low-dose (<15 g/d), middle-dose (15-47.9 g/d) and high-dose (≥48 g/d). Anthropometric measurements and serum parameters were collected. In the rat study, 27 male Wistar rats were randomly divided into 4 groups administered water or ethanol (0.5, 2.5, or 5 g·kg(-1)·d(-1)) for 22 weeks. The chemerin levels in the sera, visceral adipose tissue (VAT) and liver were measured using ELISA., Results: In the high-dose group of humans and middle- and high-dose groups of rats, chronic ethanol consumption significantly increased the serum chemerin level. Both the middle- and high-dose ethanol significantly increased the chemerin level in the VAT of rats. In humans, triglyceride, fasting glucose, insulin and HOMA-IR were independently associated with chemerin. In rats, the serum chemerin level was positively correlated with chemerin in the VAT after adjustments for the liver chemerin (r=+0.768). High-dose ethanol significantly increased the body fat in humans and the VAT in rats., Conclusion: Chronic ethanol consumption dose-dependently increases the chemerin levels in the serum and VAT. The serum chemerin level is associated with metabolic parameters in humans. The increased serum chemerin level is mainly attributed to an elevation of chemerin in the VAT after the ethanol treatment.

Aim: to investigate the potential effects of chronic ethanol intake on protein-tyrosine phosphatase-1B (PTP1B) and the insulin receptor signaling pathway in rat skeletal muscle., Methods: rats received ethanol treatment at a daily dose of 0 (control), 0.5 (group L), 2.5 (group M) or 5 gxkg(-1) (group H) via gastric gavage for 22 weeks. In vivo insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Expression of PTP1B in skeletal muscles was examined at both the mRNA (real-time PCR) and protein (Western blot) levels. PTP1B activity was assayed with a p-nitrophenol phosphate (PNPP) hydrolysis method. Changes of insulin signaling in skeletal muscle were analyzed with Western blotting., Results: the activity and expression of PTP1B were dose-dependently elevated 1.6 and 2.0 fold in the skeletal muscle by ethanol, resepctively, at the doses of 2.5 and 5 gxkg(-1)xd(-1). Total IRβ and IRS-1, as well as their phosphorylated forms, were decreased by ethanol at the two higher doses. Moreover, chronic ethanol consumption resulted in a significant inhibition of the association between IRS-1 and the p85 subunit of phosphatidylinositol 3-kinase, inhibition of Akt phosphorylation and reduced levels of mitogen-activated protein kinase phosphorylation., Conclusion: chronic ethanol intake at 2.5 and 5 xkg(-1)xd(-1) sufficient doses can down-regulate the expression of IRβ, P-IRβ, and IRS-1, as well as the phosphorylated forms of IRS-1 and Akt, in rat skeletal muscle, possibly through increased PTP1B activity.

Aim: To investigate the effects of ethanol on adipokines (leptin, adiponectin, resistin, visfatin and cartonectin) levels in visceral adipose tissue (VAT) and sera, and explore the correlation between VAT and serum adipokine levels., Methods: Forty-eight Wistar rats were randomly divided into control, low, middle and high ethanol treatment groups that received 0, 0.5, 2.5, or 5.0 g of ethanol x kg(-1) x d(-1), respectively, via gastric tubes for 22 weeks. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) were measured and homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated. Adipokines in perirenal and epididymal VAT and sera were measured by enzyme-linked immunosorbent assays (ELISAs)., Results: High-dose treatments of ethanol (vs control group) significantly increased FINS (eg 37.86%) and HOMA-IR values (eg 40.63%). In VAT, levels of leptin, resistin and visfatin in the middle- and high-dose groups were significantly elevated, whereas adiponectin and cartonectin levels decreased. In sera, changes in adipokine levels were similar to that observed in VAT, with the exception of cartonectin. These ethanol-induced effects were dose-dependent. A positive correlation existed between VAT and serum adipokine levels, except for cartonectin., Conclusion: Chronic ethanol consumption affects adipokine levels in VAT and sera in a dose-dependent manner, with the exception of serum cartonectin. The altered levels of adipokines in VAT and sera are positively correlated.

A stochastic robust interval linear programming model (IPRO) was developed for supporting municipal solid waste management under uncertainty. The model improves upon the existing stochastic robust optimization (SRO) and interval linear programming (ILP) methods by allowing evaluations of trade-offs among expected costs, cost variability, and risk of violating relax constraints simultaneously, as well as reflections of complex uncertainties through both interval and stochastic theories. A long-term waste management problem was used to demonstrate the applicability of IPRO model. The results indicated that IPRO normally led to interval solutions, where waste-management alternatives could be generated by adjusting the decision-variable values within their intervals. The model could also help waste managers to identify desired policies that under various environmental, economic, system-feasibility and system-reliability constraints.

Aim: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B., Methods: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis., Results: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change., Conclusion: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.

Present paper described the effect of human tumor necrosis factor alpha (hTNFalpha) and beta (hTNFbeta) on apoptosis induced by ionizing radiation in human embryonic lung cell line 2BS diploid cells and human lung cancer cell line A549 and SPC cells. The results showed that both hTNFalpha and hTNFbeta significantly inhibited 7Gy gamma-ray-induced apoptosis in 2BS cells. In contrast, hTNFalpha or hTNFbeta can increase the sensitivity of tumor cell lines (A549 and SPC cells) to radiation. Therefore, the results suggested that TNFalpha and TNFbeta had potential as a therapeutic agent to protect normal cell from the radiation-induced apoptosis and to sensitize the tumour cells for the damage effect of ionizing radiation.