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Patient: Female, 40-year-old Final. Diagnosis: Hepatic hydatid Symptoms: None. Medication: -- Clinical Procedure: Surgery removal. Specialty: Gastroenterology and Hepatology • Surgery. Objective: Unusual clinical course. Background: Hepatic hydatid cysts is a cystic disease of the liver caused by echinococcosis. Echinococcosis usually forms a monolocular cyst and causes space occupying effect, while alveolar echinococcosis often progresses into a polycystic mass that dilates into the adjacent liver parenchyma, with different clinical manifestations. In clinical practice, hepatic hydatid cyst and simple cyst are generally diagnosed clearly, but there are still misdiagnosed cases. Case Report: A 40-year-old female patient with no symptoms had a computed tomography and magnetic resonance imaging examination that revealed multiple round-like shadows of varying sizes in her liver. Combined with the laboratory and imaging results, the diagnosis was considered as hepatic hemangioma and hepatic cyst. Therefore, we planned to perform ultrasound guided microwave ablation of hepatic hemangioma and laparoscopic fenestration of hepatic cyst. Considering the possibility of hepatic hydatid cysts during the operation, partial hepatectomy was performed. Conclusions: More attention should be paid to the differential diagnosis of cystic space occupying lesions in the liver. For the treatment of hepatic cyst, if suspected, must change the surgical strategy. [ABSTRACT FROM AUTHOR]

N-Vinyl-3-alkylimidazolium tetrahalogenidoferrate(III) ([VRIM][FeX4], X4 = Cl3Br, Cl4) and N-vinyl-3-esterimidazolium tetrachloroferrate(III)([VEIM][FeCl4]) magnetic ionic liquids were synthesized. They were characterized by ¹H NMR, Raman, electrospray ionization mass spectrometry, differential scanning calorimetry and thermogravimetric analysis. Through Gaussian09/B3LYP/LANL2DZ density functional theory, the interaction energies of ion pairs and dipole moment of [VRIM][FeX4] and [VEIM][FeCl4] were obtained. The relationships between the surface tensions and temperature, molecular structure, and interaction energies of ion pairs along with the relationships between the solubility and molecular structure, common solvents, and interaction energies of ion pairs were discussed systematically. The relationship between the surface tensions and solubility parameter for [VRIM][FeX4] was expressed by using a Hildebrand-Scoff equation. And the hydrophilic-lipophilic balance (HLB) values of [VRIM][FeX4] were obtained by a solubility parameter. The results showed that surface tension decreased linearly with temperature and decreased with the elongation of alkyl chain length on cation and the decrease of interaction energies of ion pairs; With decreasing dielectric constant of solvent, the solubility of the title magnetic ionic liquids increased first and then decreased; with the elongation of alkyl chain length, the interaction energies of ion pairs and HLB value decreased, and the solubility in polar solvents had a decreasing trend. [ABSTRACT FROM AUTHOR]

N-Vinyl-3-alkylimidazolium tetrahalogenidoferrate(III) ([VRIM][FeX4], X4 = Cl3Br, Cl4) and N-vinyl-3-esterimidazolium tetrachloroferrate(III)([VEIM][FeCl4]) magnetic ionic liquids were synthesized. They were characterized by ¹H NMR, Raman, electrospray ionization mass spectrometry, differential scanning calorimetry and thermogravimetric analysis. Through Gaussian09/B3LYP/LANL2DZ density functional theory, the interaction energies of ion pairs and dipole moment of [VRIM][FeX4] and [VEIM][FeCl4] were obtained. The relationships between the surface tensions and temperature, molecular structure, and interaction energies of ion pairs along with the relationships between the solubility and molecular structure, common solvents, and interaction energies of ion pairs were discussed systematically. The relationship between the surface tensions and solubility parameter for [VRIM][FeX4] was expressed by using a Hildebrand-Scoff equation. And the hydrophilic-lipophilic balance (HLB) values of [VRIM][FeX4] were obtained by a solubility parameter. The results showed that surface tension decreased linearly with temperature and decreased with the elongation of alkyl chain length on cation and the decrease of interaction energies of ion pairs; With decreasing dielectric constant of solvent, the solubility of the title magnetic ionic liquids increased first and then decreased; with the elongation of alkyl chain length, the interaction energies of ion pairs and HLB value decreased, and the solubility in polar solvents had a decreasing trend. [ABSTRACT FROM AUTHOR]

Novel types of polymeric membranes containing molecular recognition sites for selective recognition of lysozyme (Lyz) have been prepared using a surface-initiated atom transfer radical polymerization approach. The surface compositions of the regenerated cellulose (RC) membranes before and after polymerization were characterized by X-ray photoelectron spectroscopy analysis, which demonstrated that the molecular imprinting layer was successfully fabricated onto the surface of RC membranes. The selective recognition of Lyz molecularly imprinted membranes (Lyz-MIMs) for Lyz was evaluated by protein adsorption penetration tests. It was found that Lyz-MIMs have excellent adsorption capacity and specific recognition for Lyz adsorption from aqueous solutions. In the presence of competitive substances, a separation factor of 23.08 was achieved. The molecularly imprinted RC composite membrane is promising for separation and purification of specific protein compositions in biosamples. In addition, it may have good prospect for enriching target protein, which requires further study. [ABSTRACT FROM AUTHOR]

Abstract: In this article, the preparation of porous PVA membranes by the supercritical CO2 fluid was introduced. The effects of pressure, temperature, and action time of the supercritical CO2 fluid have been studied on membrane transport parameters, viz. pure water flux, PEG600 transport parameter. It has been concluded that under difference supercritical CO2 fluid conditions, difference membrane structure was developed, which were also summarized in this article. [Copyright &y& Elsevier]

This paper reports the completion of the first expansion phase of the Sheffield Corpus of Chinese (SCC). We describe the major improvements we made in expanding the corpus. They involve the coverage of time periods, choice of text types and categories, and selection of individual texts; the mark up scheme and the integral search and analysis tool. We use the developing SCC to examine Li and Thompson's (1974, 1975, 1976) controversial postverbal predominance hypothesis for prepositional phrases (PPs) in Archaic Chinese and their word order change hypothesis for PPs in general in the history of the Chinese language. Our study provides no evidence for the postverbal predominance hypothesis for PPs in Archaic Chinese and the word order change hypothesis for PPs in general from postverbal in Archaic Chinese to preverbal in Modern Chinese. Our findings show that postverbal and preverbal PPs have been in coexistence and there have always been more occurrences of preverbal PPs than postverbal PPs in all the time periods covered in the current SCC. Although use of some PPs declined in some time periods and use of others emerged in other time periods, there was never a predominant position for PPs in any time period in the history of Chinese. We show differences in the distribution of PPs in different time periods and provide an account of the syntactic positions of PPs in those time periods. [ABSTRACT FROM AUTHOR]

This study investigates the second language (L2) acquisition of restrictive relative clauses (RRCs) in Chinese by two groups of learners speaking typologically different first languages (L1s): English and Korean. English RRCs, unlike those of Chinese, are head-initial whereas Korean RRCs, like those of Chinese, are head-final. The difference could be predicted to hinder English learners' acquisition of L2 RRCs but facilitate it for Korean learners. This prediction was not confirmed in this study, in fact the reverse was observed, and our data show contrasting patterns of acquisition between the two groups of learners. The English learners distinguished between target-like RRCs and non-target-like RRCs earlier than the Korean learners. A corresponding difference was observed for acquisition of resumptive pronouns. It is argued that where the L1 and the L2 share salient properties (such as head direction) restructuring of less salient features encoded in functional categories takes longer and may be persistently problematic. We suggest that the fact that Korean is more similar to Chinese (perhaps superficially, same head direction) leads learners not to restructure quickly, while the surface dissimilarity of English and Chinese gives rise to rapid restructuring in L2 grammars of learners. [ABSTRACT FROM AUTHOR]

The paper presents the outcome of the pilot phase of a major project which aims to build a digital resource for the study of historical Chinese texts with a view to facilitating linguistic analysis of the language, particularly from a diachronic point of view. The approach to general problems for a diachronic corpus is discussed. Details of the tag set and the tagging system devised are given. The development of a sophisticated automatic mark-up scheme for Chinese texts from widely different time periods and genres is indicated. [ABSTRACT FROM AUTHOR]

The article discusses that Cellular metabolism has been proposed to govern distinct γδ T cell effector functions, but the underlying molecular mechanisms needs further research. Interleukin-17 (IL-17)–producing γδT17 and interferon-#947;(IFN-γ)–producing γδT (γδT1) cells have differential metabolic requirements and the rate-limiting enzyme isocitrate dehydrogenase 2 (IDH2) acts as a metabolic checkpoint for their effector functions.

Regulation of myeloid-derived suppressor cells (MDSC) by ongoing inflammation following repeated chemotherapy remain elusive. In this study, we show that a multidose clinical regimen of gemcitabine (GEM) treatment enhances the immunosuppressive function of monocytic MDSC (M-MDSC), although tumor development is delayed in E0771 tumor-bearing mice. Accordingly, effector IFN-γ-producing CD4 and CD8 T cells are significantly decreased in the tumor microenvironment (TME) of GEM-treated mice. The conditioned medium of GEM-treated tumor cells enhances differentiation of mouse bone marrow cells and human PBMC into immunosuppressive M-MDSC. Cytokine profiling of GEM-treated tumor cells identifies GM-CSF as one of the most differentially expressed cytokines. Blockade or knockdown of GM-CSF can partially reduce immunosuppression of Ly6Chigh cells induced by GEM-conditioned medium. Knockdown of GM-CSF in tumor cells also delays tumor progression with decreased accumulation of M-MDSC in the TME. Mechanistically, enhanced production of reactive oxygen species and activation of NF-κB are observed in GEM-treated tumor cells. Treatment with the mitochondrial-targeted antioxidant and inhibitor of NF-κB signaling can abrogate GEM-induced hyperexpression of GM-CSF in E0771 cells. In addition, the phagocytic clearance of apoptotic tumor cells (efferocytosis) enhances the immunosuppressive function of bone marrow Ly6Chigh myeloid cells. Further, GEM treatment results in metabolic changes in residual tumor cells, leading to the resistance to T cell-mediated killing. Together, our results define an undesired effect of repeated GEM treatment promoting immunosuppression in TME via upregulation of GM-CSF and efferocytosis as well as deregulation of lipid metabolism in residual tumor cells. [ABSTRACT FROM AUTHOR]

The present study investigated the clinical effect of antibiotic de-escalation therapy in elderly patients with chronic obstructive pulmonary disease (COPD) complicated with severe pneumonia. According to the parity method of hospitalization number, 86 cases were selected and divided into the observation and control group with 43 cases each. Based on empirical antibiotic application, levofloxacin and cephalosporin antibiotics were used in the control group. After treatment for 3 days, the regimen was adjusted to antibiotics active against Gram-positive (G+) and Gram-negative (G-) bacteria such as the third or fourth generation cephalosporin antibiotics, combined with aminoglycoside, or macrolide antibiotics according to their effects. The treatment effects were re-evaluated after 3-7 days. Finally, broad-spectrum antibiotics such as imipenem were chosen or adjusted by bacterial cultures and drug sensitivity results in the control group. Patients in the observation group were treated according to the principle of antibiotic de-escalation therapy. Antibiotics active against G+ and G- bacteria were chosen as the first round of medication. After 3 days, broad-spectrum antibiotics such as imipenem were added to the treatment regimen. After 7 days, the treatment was changed to narrow spectrum antibiotic administration if the disease was in remission, and the antibiotic regimen was adjusted based on bacterial culture and drug sensitivity results. The treatment results were compared. The mechanical ventilation rate, antibiotic courses, number of antibiotics used, and mortality of the observation group were significantly lower than those in the control group (P<0.05). After treatment, lung function improved, partial pressure of oxygen and blood oxygen saturation increased, and partial pressure of carbon dioxide decreased in both groups. The improvement of all of the above parameters were more significant in the observation group (P<0.05). After treatment, the ratio of neutrophils over white blood cells and C-reactive protein levels of the two groups decreased, respiratory failure index (RFI) increased, and the changes were significantly more pronounced in the observation group (P<0.05). In conclusion, following the antibiotic de-escalation principle to treat older patients with COPD complicated with severe pneumonia can reduce the number of antibiotics required, improve lung function and clinical effects, and is safe and effective. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted rehabilitation is an advanced new technology in stroke rehabilitation to provide intensive training. Post-stroke motor recovery depends on active rehabilitation by voluntary participation of patient's paretic motor system as early as possible in order to promote reorganization of brain. However, voluntary residual motor efforts to the affected limb have not been involved enough in most robot-assisted rehabilitation for patients after stroke. The objective of this study is to evaluate the feasibility of robot-assisted rehabilitation using myoelectric control on upper limb motor recovery. Methods: In the present study, an exoskeleton-type rehabilitation robotic system was designed to provide voluntarily controlled assisted torque to the affected wrist. Voluntary intention was involved by using the residual surface electromyography (EMG) from flexor carpi radialis(FCR) and extensor carpi radialis (ECR)on the affected limb to control the mechanical assistance provided by the robotic system during wrist flexion and extension in a 20- session training. The system also applied constant resistant torque to the affected wrist during the training. Sixteen subjects after stroke had been recruited for evaluating the tracking performance and therapeutical effects of myoelectrically controlled robotic system. Results: With the myoelectrically-controlled assistive torque, stroke survivors could reach a larger range of motion with a significant decrease in the EMG signal from the agonist muscles. The stroke survivors could be trained in the unreached range with their voluntary residual EMG on the paretic side. After 20-session rehabilitation training, there was a non-significant increase in the range of motion and a significant decrease in the root mean square error (RMSE) between the actual wrist angle and target angle. Significant improvements also could be found in muscle strength and clinical scales. Conclusions: These results indicate that robot-aided therapy with voluntary participation of patient's paretic motor system using myoelectric control might have positive effect on upper limb motor recovery. [ABSTRACT FROM AUTHOR]

Abstract  We previously showed that cultured mouse cerebellar granule cells during incubation in glutamine-replete medium respond to 45 mM [K+]e after 20 and 60 min incubation with extracellular-signal regulated kinase 1 and 2 (ERK1/2) phosphorylation which is mainly, but probably not exclusively, secondary to glutamate release and transactivation of epidermal growth factor (EGF) receptors. In the present study the response after 20 min was shown to be abolished by protein kinase C (PKC) inhibition, whereas that at 60 min was PKC-independent. Addition of 50 μM glutamate to the cells caused ERK1/2 phosphorylation already after 5 min most of which was sensitive to PKC inhibition although a minor part was PKC inhibition-resistant. Exposure to [K+]e during incubation in glutamine-depleted medium caused no stimulated release of glutamate but a transactivation-independent ERK1/2 phosphorylation at 20 and 60 min. The response at 20 min was insensitive to PKC inhibition. The potential importance of these complex responses for synaptic plasticity is discussed. [ABSTRACT FROM AUTHOR]

Background: High-mobility group box-1 (HMGB1), a nuclear protein, plays an important role in the pathogenesis of Henoch-Schonlein purpura (HSP). In a Chinese child population, the correlation between susceptibility to HSP and genetic variation in the HMGB1 gene and also the relationship between HMGB1 gene polymorphism and clinical heterogeneity of HSP were investigated. Methods: We analyzed two HMGB1 tag single nucleotide polymorphisms (SNPs; rs3742305 and rs95 08752) in 182 HSP patients and 202 healthy controls using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. Results: There were no significant differences between HSP patients and controls in the frequency of alleles, genotypes, and hap-lotypes of HMGB1 SNPs. In addition, there was a slight association between HMGB1 gene polymorphisms and the clinical manifestations of HSP. Conclusions: It is suggested that the variation of the HMGB1 gene was not highly correlated with the susceptibility of Chinese children to HSP. [ABSTRACT FROM AUTHOR]

The amyloid-β peptide (1-42) (Aβ42) can provide high diagnostic accuracy for the early diagnosis of Alzheimer's disease (AD). In this study, an immunosensor based on the peroxidase-like activity of heme-Aβ42 was designed for Aβ42 detection. The glassy carbon electrode (GCE) was electrodeposited Au particles (GCE/Au). The GCE/Au was modified using polythionine-methylene blue (PTH-MB), AuNPs, monoclonal antibody (anti-Aβ42), and bovine serum albumin (BSA), successively. The GCE/Au/PTH-MB/AuNPs/anti-Aβ42/BSA could competitively recognize Aβ42 and heme-Aβ42. The anchored heme-Aβ42 showed strong electrocatalytic activity between H2O2 and ferrocenemethanol. Under optimum conditions, we determined detection limits of 17.3 pM in PBS pH 7, 25.2 pM in serum, and 23.8 pM in saliva. The recovery ranged from 71.0% to 117.8%. [ABSTRACT FROM AUTHOR]

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound β-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or lossof- function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase rep orter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were r eversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, h ighlighting its potential as a therapeutic target for DPN. [ABSTRACT FROM AUTHOR]

The role of the mTOR signaling pathway in different myeloid cell subsets is poorly understood in the context of tumor development. In this study, myeloid cell-specific Raptor knockout (KO) mice were used to determine the roles of mechanistic target of rapamycin complex 1 (mTORC1) in regulating macrophage function from Lewis lung carcinoma (LLC) s.c. tumors and lung tumor metastasis. We found no difference in tumor growth between conditional Raptor KO and control mice in the s.c. tumor models, although depletion of mTORC1 decreased the immunosuppressive function of tumor-associated macrophages (TAM). Despite the decreased immunosuppressive activity of TAM, M1-like TAM differentiation was impaired in the s.c. tumor microenvironment of mTORC1 conditional Raptor KO mice due to downregulated CD115 expression on macrophages. In addition, TNF-α production by mTORC1-deficient myeloid cells was also decreased in the s.c. LLC tumors. On the contrary, disruption of mTORC1 in myeloid cells promoted lung cancer metastasis. Accordingly, immunosuppressive interstitial macrophages/metastasis-associated macrophages (CD11b+F4/80high) were accumulated in the lungs of Raptor KO mice in the LLC lung metastasis model, leading to decreased Th1 responses. Taken together, our results demonstrate that differential tumor microenvironment dictates the immunological outcomes of myeloid cells, with mTORC1 disruption leading to different tumor growth phenotypes. [ABSTRACT FROM AUTHOR]

Background: It is a challenge to reduce the muscular discoordination in the paretic upper limb after stroke in the traditional rehabilitation programs.Method: In this study, a neuromuscular electrical stimulation (NMES) and robot hybrid system was developed for multi-joint coordinated upper limb physical training. The system could assist the elbow, wrist and fingers to conduct arm reaching out, hand opening/grasping and arm withdrawing by tracking an indicative moving cursor on the screen of a computer, with the support from the joint motors and electrical stimulations on target muscles, under the voluntary intention control by electromyography (EMG). Subjects with chronic stroke (n = 11) were recruited for the investigation on the assistive capability of the NMES-robot and the evaluation of the rehabilitation effectiveness through a 20-session device assisted upper limb training.Results: In the evaluation, the movement accuracy measured by the root mean squared error (RMSE) during the tracking was significantly improved with the support from both the robot and NMES, in comparison with those without the assistance from the system (P < 0.05). The intra-joint and inter-joint muscular co-contractions measured by EMG were significantly released when the NMES was applied to the agonist muscles in the different phases of the limb motion (P < 0.05). After the physical training, significant improvements (P < 0.05) were captured by the clinical scores, i.e., Modified Ashworth Score (MAS, the elbow and the wrist), Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT).Conclusions: The EMG-driven NMES-robotic system could improve the muscular coordination at the elbow, wrist and fingers.Trial Registration: ClinicalTrials.gov. NCT02117089 ; date of registration: April 10, 2014. [ABSTRACT FROM AUTHOR]

Ab maturation as well as memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop as a result of enhanced GC activity. Previous studies have shown that the dysregulated STAT3 pathway is linked to lupus pathogenesis. However, the exact role of STAT3 in regulating SLE disease progression has not been fully understood. In this study, we demonstrated that STAT3 signaling in B cells is essential for GC formation and maintenance as well as Ab response. Increased cell apoptosis and downregulated Bcl-xL and Mcl-1 antiapoptotic gene expression were found in STAT3-deficient GC B cells. The follicular helper T cell response positively correlated with GC B cells and was significantly decreased in immunized B cell STAT3-deficient mice. STAT3 deficiency also led to the defect of plasma cell differentiation. Furthermore, STAT3 deficiency in autoreactive B cells resulted in decreased autoantibody production. Results obtained from B cell STAT3-deficient B6.MRL/lpr mice suggest that STAT3 signaling significantly contributes to SLE pathogenesis by regulation of GC reactivity, autoantibody production, and kidney pathology. Our findings provide new insights into the role of STAT3 signaling in the maintenance of GC formation and GC B cell differentiation and identify STAT3 as a novel target for treatment of SLE. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80+CD11c+ cells in vitro that served as potent APC to induce Ag-specific CD4+ and CD8+ T cell responses in a dectin-1-dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c+ cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non-small cell lung carcinoma that had received WGP treatment for 10-14 d prior to any other treatment had a decreased frequency of CD14-HLA-DR-CD11b+CD33+ MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. Results: Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. Conclusions: Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced spleen tyrosine kinase-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared with those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed light on the action mode of β-glucan treatment in cancer. [ABSTRACT FROM AUTHOR]

Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. In this article, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single-chain variable fragment miniAb. Using the tumor-associated Ag her-2/neu extracellular domain, we showed that the coengagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinoma models. Furthermore, four different extracellular domains of her-2/neu could be targeted to B cells to generate Abs against particular domains with different antitumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost, which may be of use not only for cancer therapy but also for infectious agents. [ABSTRACT FROM AUTHOR]

Active rehabilitation involves patient's voluntary thoughts as the control signals of restore device to assist stroke rehabilitation. Although restoration of hand opening stands importantly in patient's daily life, it is difficult to distinguish the voluntary finger extension from thumb adduction and finger flexion using stroke patients' electroencephalography (EMG) on singlemuscle activity. We propose to implement corticomuscular coherence analysis on electroencephalography (EEG) and EMG signals on Extensor Digitorum to extract their intention involved in hand opening. EEG and EMG signals of 8 subjects are simultaneously collected when executing 4 hand movement tasks (finger extension, thumb adduction, finger flexion, and rest). We explore the spatial and temporal distribution of the coherence and observe statistically significant corticomuscular coherence appearing at left motor cortical area and different patterns within beta frequency range for 4 movement tasks. Linear discriminate analysis is applied on the coherence pattern to distinguish finger extension from thumb adduction, finger flexion, and rest. The classification results are greater than those by EEG only. The results indicate the possibility to detect voluntary hand opening based on coherence analysis between single muscle EMG signal and single EEG channel located in motor cortical area, which potentially helps active hand rehabilitation for stroke patients. [ABSTRACT FROM AUTHOR]

Binding of a new thyroid-stimulating human monoclonal autoantibody (MAb) K1-18 to the TSH receptor (TSHR) leucinerich domain (LRD) was predicted using charge-charge interaction mapping based on unique complementarities between the TSHR in interactions with the thyroid-stimulating human MAb M22 or the thyroid-blocking human MAb K1-70. The interactions of K1-18 with the TSHR LRD were compared with the interactions in the crystal structures of the M22-TSHR LRD and K1-70-TSHR LRD complexes. Furthermore, the predicted position of K1-18 on the TSHR was validated by the effects of TSHR mutations on the stimulating activity of K1-18. A similar approach was adopted for predicting binding of a mouse thyroid-blocking MAb RSR-B2 to the TSHR. K1-18 is predicted to bind to the TSHR LRD in a similar way as TSH and M22. The binding analysis suggests that K1-18 light chain (LC) mimics binding of the TSH-α chain and the heavy chain (HC) mimics binding of the TSH-β chain. By contrast, M22 HC mimics the interactions of TSH-α while M22 LC mimics TSH-β in interactions with the TSHR. The observed interactions in the M22-TSHR LRD and K1-70-TSHR LRD complexes (crystal structures) with TSH-TSHR LRD (comparative model) and K1-18-TSHR LRD (predictive binding) suggest that K1-18 and M22 interactions with the receptor may reflect interaction of thyroid-stimulating autoantibodies in general. Furthermore, K1-70 and RSR-B2 interactions with the TSHR LRD may reflect binding of TSHR-blocking autoantibodies in general. Interactions involving the C-terminal part of the TSHR LRD may be important for receptor activation by autoantibodies. [ABSTRACT FROM AUTHOR]

Promoting complement (C) activation may enhance immunological mechanisms of anti-tumor Abs for tumor destruction. However, C activation components, such as C5a, trigger inflammation, which can promote tumor growth. We addressed the role of C5a on tumor growth by transfecting both human carcinoma and murine lymphoma with mouse C5a. In vitro growth kinetics of C5a, control vector, or parental cells revealed no significant differences. Tümor-bearing mice with C5a-transfected xenografted tumor cells had significantly less tumor burden as compared with control vector tumors. NK cells and macrophages infiltrated C5a-expressing tumors with significantly greater frequency, whereas vascular endothelial growth factor, arginase, and TNF-&agr; production were significantly less. Tumor-bearing mice with high C5a-producing syngeneic lymphoma cells had significantly accelerated tumor progression with more Gr-l+CDllb+ myeloid cells in the spleen and overall decreased CD4+ and CD8+ T cells in the tumor, tumor-draining lymph nodes, and the spleen. In contrast, tumor-bearing mice with low C5a-producing lymphoma cells had a significantly reduced tumor burden with increased IFN-&ggr;-producing CD4+ and CD8+ T cells in the spleen and tumor-draining lymph nodes. These studies suggest concentration of local C5a within the tumor microenvironment is critical in determining its role in tumor progression. [ABSTRACT FROM AUTHOR]

Objective Patients who appear to have both stimulating and blocking TSHR autoantibodies in their sera have been described, but the two activities have not been separated and analysed. We now describe the isolation and detailed characterization of a blocking type TSHR monoclonal autoantibody and a stimulating type TSHR monoclonal autoantibody from a single sample of peripheral blood lymphocytes. Design, patients and measurements Two heterohybridoma cell lines secreting TSHR autoantibodies were isolated using standard techniques from the lymphocytes of a patient with hypothyroidism and high levels of TSHR autoantibodies (160 units/l by inhibition of TSH binding). The ability of the two new monoclonal antibodies (MAbs; K1-18 and K1-70) to bind to the TSHR and compete with TSH or TSHR antibody binding was analysed. Furthermore, the effects of K1-18 and K1-70 on cyclic AMP production in Chinese hamster ovary cells (CHO) cells expressing the TSHR were investigated. Results One MAb (K1-18) was a strong stimulator of cyclic AMP production in TSHR-transfected CHO cells and the other (K1-70) blocked stimulation of the TSHR by TSH, K1-18, other thyroid-stimulating MAbs and patient serum stimulating type TSHR autoantibodies. Both K1-18 (IgG1 kappa) and K1-70 (IgG1 lambda) bound to the TSHR with high affinity (0·7 × 1010 l/mol and 4 × 1010 l/mol, respectively), and this binding was inhibited by unlabelled K1-18 and K1-70, other thyroid-stimulating MAbs and patient serum TSHR autoantibodies with stimulating or blocking activities. V region gene analysis indicated that K1-18 and K1-70 heavy chains used the same V region germline gene but different D and J germline genes as well as having different light chains. Consequently, the two antibodies have evolved separately from different B cell clones. Conclusions This study provides proof that a patient can produce a mixture of blocking and stimulating TSHR autoantibodies at the same time. [ABSTRACT FROM AUTHOR]

AbstractContusive spinal cord injury (SCI) is the most common type of spinal injury seen clinically. Several rat contusion SCI models have been described, and all have strengths and weaknesses with respect to sensitivity, reproducibility, and clinical relevance. We developed the Louisville Injury System Apparatus (LISA), which contains a novel spine-stabilizing device that enables precise and stable spine fixation, and is based on tissue displacement to determine the severity of injury. Injuries graded from mild to moderately severe were produced using 0.2-, 0.4-, 0.6-, 0.8-, 1.0-, and 1.2-mm spinal cord displacement in rats. Basso, Beattie, and Bresnahan (BBB) and Louisville Swim Score (LSS) could not significantly distinguish between 0.2-mm lesion severities, except those of 0.6- and 0.8-mm BBB scores, but could between 0.4-mm injury differences or if the data were grouped (0.2–0.4, 0.6–0.8, and 1.0–1.2). Transcranial magnetic motor evoked potential (tcMMEP) response amplitudes were decreased 10-fold at 0.2-mm displacement, barely detected at 0.4-mm displacement, and absent with greater displacement injuries. In contrast, somatosensory evoked potentials (SSEPs) were recorded at 0.2- and 0.4-mm displacements with normal amplitudes and latencies but were detected at lower amplitudes at 0.6-mm displacement and absent with more severe injuries. Analyzing combined BBB, tcMMEP, and SSEP results enabled statistically significant discrimination between 0.2-, 0.4-, 0.6-, and 0.8-mm displacement injuries but not the more severe injuries. Present data document that the LISA produces reliable and reproducible SCI whose parameters of injury can be adjusted to more accurately reflect clinical SCI. Moreover, multiple outcome measures are necessary to accurately detect small differences in functional deficits and/or recovery. This is of crucial importance when trying to detect functional improvement after therapeutic intervention to treat SCI. [ABSTRACT FROM AUTHOR]

In order to facilitate the broad applications of molecular recognition materials in biomedical areas, it is critical to enhance their adsorption capacity while maintaining their excellent recognition performance. In this work, we designed and synthesized well-defined peptide-imprinted mesoporous silica (PIMS) for specific recognition of an immunostimulating hexapeptide from human casein (IHHC) by using amphiphilic ionic liquid as the surfactant to anchor IHHC via a combination of one-step sol–gel method and docking oriented imprinting approach. Thereinto, theoretical calculation was employed to reveal the multiple binding interactions and dual-template configuration between amphiphilic ionic liquid and IHHC. The fabricated PIMS was characterized and an in-depth analysis of specific recognition mechanism was conducted. Results revealed that both adsorption and recognition capabilities of PIMS far exceeded that of the NIMS’s. More significantly, the PIMS exhibited a superior binding capacity (60.5 mg g−1), which could increase 18.9% than the previous work. The corresponding imprinting factor and selectivity coefficient could reach up to 4.51 and 3.30, respectively. The PIMS also possessed lickety-split kinetic binding for IHHC, where the equilibrium time was only 10 min. All of these merits were due to the high surface area and the synergistic effect of multiple interactions (including hydrogen bonding, π–π stacking, ion–ion electrostatic interactions and van der Waals interactions, etc) between PIMS and IHHC in imprinted sites. The present work suggests the potential application of PIMS for large-scale and high-effective separation of IHHC, which may lead to their broad applications in drug/gene deliver, biosensors, catalyst and so on. [ABSTRACT FROM AUTHOR]