A study of multinucleated giant cells in esophageal cancer

Objectives: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multi-nucleated giant cell (MGC) in esophageal cancer. Materials and methods: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. Results: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). Conclusions: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker

Atmospheric new particle formation from sulfuric acid and amines in a Chinese megacity

Atmospheric new particle formation (NPF) is an important global phenomenon that is nevertheless sensitive to ambient conditions. According to both observation and theoretical arguments, NPF usually requires a relatively high sulfuric acid (H2SO4) concentration to promote the formation of new particles and a low preexisting aerosol loading to minimize the sink of new particles. We investigated NPF in Shanghai and were able to observe both precursor vapors (H2SO4) and initial clusters at a molecular level in a megacity. High NPF rates were observed to coincide with several familiar markers suggestive of H2SO4-dimethylamine (DMA)water (H2O) nucleation, including sulfuric acid dimers and H2SO4-DMA clusters. In a cluster kinetics simulation, the observed concentration of sulfuric acid was high enough to explain the particle growth to similar to 3 nanometers under the very high condensation sink, whereas the subsequent higher growth rate beyond this size is believed to result fromthe added contribution of condensing organic species. These findings will help in understanding urban NPF and its air quality and climate effects, as well as in formulating policies to mitigate secondary particle formation in China.Peer reviewe

Atrial Fibrillation Follow-up Investigation to Recover Memory and Learning Trial (AFFIRMING): Rationale and Design of a Multi-center, Double-blind, Randomized Controlled Trial

Background: People with atrial fibrillation (AF) have elevated risk of developing cognitive impairment. At present, there is a dearth of randomized controlled trials investigating cognitive impairment management in patients with AF. The Atrial Fibrillation Follow-up Investigation to Recover Memory and learning (AFFIRMING) study is aimed at evaluating the potential for computerized cognitive training to improve cognitive function in patients with AF. Methods: The study is a multi-center, double-blind, randomized controlled study using a 1:1 parallel design. A total of 200 patients with AF and mild cognitive decline without dementia are planned to be recruited. The intervention group will use the adaptive training software with changes in difficulty, whereas the positive control group will use basic training software with minimal or no variation in difficulty level. At the end of 12 weeks, the participants will be unblinded, and the positive control group will stop training. The intervention group will be rerandomized 1:1 to stop training or continue training. All participants will be followed up until 24 weeks. The primary endpoint is the proportion of the improvement of the global cognitive function at week 12 compared with baseline, using the Basic Cognitive Ability Test (BCAT)

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function

XPS study on the selective wet etching mechanism of GeSbTe phase change thin films with tetramethylammonium hydroxide

Phase change lithography has pretty potential applications for high density optical data storage mastering and micro/nano structure patterning because it is not restricted by optical diffraction limitation and at relatively low cost. GeSbTe, as an initially investigated material for phase change lithography, its mechanism of selective etching in inorganic or organic alkaline aqueous solutions, such as NaOH and tetramethylammonium hydroxide (TMAH), is still unknown. In this paper, XPS measurement is used to study the selective wet etching mechanism of GeSbTe phase change thin films with TMAH solution, and the results show that oxidization played an important role in the etching process. Ge, Sb and Te are oxidized into GeO2, Sb2O5 and TeO2, respectively, and then as the corresponding salts dissolved into the etchant solution. Ge-X (X is Ge, Sb or Te) bonds are first broken in the etching, then Sb-X bonds, and finally Te-Te bonds. To confirm the effect of oxidization in the etching, H2O2 as an oxidant is added into the TMAH solution, and the etching rates are increased greatly for both amorphous and crystalline states. The selective etching mechanism of Ge2Sb2Te5 phase change films is discussed by the difference of bonds breakage between the amorphous and crystalline states

Intramolecular Glycosidation by Click Reaction Mediated Spacer Generation and Following Spacer Cleavage

2-O-Propargyl-substituted glycosyl donors and O-(2-azidobenzyl)-substituted acceptors having a vicinal hydroxy group readily underwent the click reaction. Intramolecular glycosidation with N-iodosuccinimide/trifluoromethansulfonic acid as the activating system afforded β-(1–3)- and α-(1–2)-linked disaccharides as part of 14-membered macrocycles. Descriptors for these reactions are proposed that consider the donor and acceptor attachment sites and the stereochemistry of the functional groups. Investigation of the influence of 2-O-linked 1-aryl-1,2,3-triazol-4-ylmethyl groups, as contained in the spacer, on the anomeric selectivity exhibited no anchimeric assistance. In addition, it was shown that the spacer group can be readily cleaved under Birch reduction conditions

Microglia/Macrophages and CD4+CD25+ T Cells Enhance the Ability of Injury-Activated Lymphocytes to Reduce Traumatic Optic Neuropathy In Vitro

Inflammation after acute CNS injury plays a dual role. The interplay between immune cells and inflammatory mediators is critical to the outcome of injured neurons. Microglia/macrophages are the first sensors and regulators of the immune response. We previously found that the enhancement of macrophages on neuron survival does not persist in thymectomized rats. How T lymphocytes and macrophages interact and benefit neuron survival is not fully elucidated. To this point, we introduce and characterize a cell-retina co-culture model that mimics the recruitment of peripheral lymphocytes at the injury site. Three-day post-optic nerve transection (ONT) in Fischer 344 rats, transected retinas were co-cultured with either peripheral lymph node-derived lymphocytes (injury-activated) or from intact rats as the control. The injury-activated lymphocytes preserved retinal ganglion cells (RGCs) and caused extensive retina microglial/macrophage infiltration. CD4+CD25+ T cells were upregulated in the injury-activated lymphocytes and increased RGC survival, suggesting that CD4+CD25+ T cells suppressed the cytotoxicity of control lymphocytes. When microglia/macrophages were depleted by clodronate, neuron loss was more extensive, the cytotoxicity of control lymphocytes on RGCs was alleviated, and the neuroprotective effect of injury-activated lymphocytes remain unchanged Cytokine detection showed an increase in IL-6 and TNF-α levels that were reduced with microglia/macrophage depletion. Our results suggest that microglial/macrophage infiltration into axotomized retinas promotes RGC survival by secreting cytokines to induce CD4+CD25+ T cells and suppress T cell-mediated RGC toxicity. These findings reveal a specific role for microglia/macrophage and CD4+CD25+ T cells in inflammation after CNS injury, thereby adding to the mechanistic basis for the development of microglial/macrophage modulation therapy for traumatic CNS injury

Lewis Acids as α-Directing Additives in Glycosylations by Using 2,3-<i>O</i>-Carbonate-Protected Glucose and Galactose Thioglycoside Donors Based on Preactivation Protocol

Catalytic or stoichiometric amounts of Lewis acids were found to be very effective α-directing additives in the stereoselective glycosylations of diverse 2,3-<i>O</i>-carbonate-protected glucose and galactose thioglycoside donors by preactivation protocol. The poor stereoselectivities of 4,6-di-<i>O</i>-acetyl-2,3-<i>O</i>-carbonate protected thioglycoside donors in glycosyl coupling reactions were greatly improved, and excellent α-stereoselectivities were achieved by the addition of 0.2 equiv of BF₃·OEt₂. On the other hand, the β-selectivities of 4,6-di-<i>O</i>-benzyl-2,3-<i>O</i>-carbonate-protected thioglucoside donor toward glycosylations were reversed completely to the α-selectivities by the use of 1 equiv of SnCl₄, making the stereoselectivity controllable. Furthermore, the poor stereoselectivities of 4,6-di-<i>O</i>-benzyl-2,3-<i>O</i>-carbonate-protected thiogalactoside donor in glycosylations were also improved by using SnCl₄ as additive

The involvement of sirtuins during optic nerve injury of rats

Sirtuins, comprised of seven members, protect cells from injury, possibly through different roles. In this study, we used two young rat optic nerve injury models to analyze the changes in Sirts 1-7 at different time points to better understand the role of sirtuins during optic nerve injury. Twelve-week-old adult male F344 rats (total n=42) were divided randomly into two groups. One group was subjected to optic nerve cut (ON-cut) and the other group was subjected to a peripheral nerve-optic nerve graft (PN-ON graft) on the left eye. At 1 and 3 days and 1, 2, and 4 weeks, rats were euthanized and retinas of both eyes were removed. Total RNA was extracted and first-strand cDNA was synthesized. Sirts 1-7 and housekeeping -actin quantitative real-time PCR were performed. The quantitative real-time PCR profile showed that sirtuin mRNAs in both groups increased following optic nerve injury with and without peripheral nerve grafting. Sirt1 mRNA increased rapidly, reaching its peak at 3 days after surgery. Sirts 2-7 showed an increasing trend and remained high through 4 weeks after surgery. Sirts 4 and 6 were the only Sirts that increased in number in the PN-graft group at 4 weeks after surgery, where neuronal survival should be higher. Our data indicate that Sirt1 and Sirts 2-7 may play different or complementary roles in optic nerve injury and that Sirts 4 and 6 may play a greater role than the remaining Sirts in axon regeneration