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Purpose:To describe photoreceptor damage in patients withTerson syndromeas a potential cause for inconsistent clinical outcomes. Methods:Clinical evaluation and retinal imaging in six patients Results:Four patients were female and two male, with an average age of 46.8 years (SD 8.9). Four patients suffered aneurysmal subarachnoid haemorrhage, one vertebral artery dissection, and one superior sagittal sinus thrombosis. In 11 eyes, we observed a consistent pattern of outer retinal damage within the central macula affecting the ellipsoid zone and the outer nuclear layer, indicating photoreceptor damage. Areas of photoreceptor damage showed poor spatial correlation with intraocular haemorrhage, particularly sub-internal limiting membrane haemorrhage. The observed retinal abnormalities demonstrated incomplete recovery over long-term follow-up 3.5 to 8 years post-haemorrhage, irrespective of surgical or conservative treatment strategy, and had variable impact on the patients’ visual function. Conclusion:The observations suggest that photoreceptor damage inTerson syndromelikely represents a distinct manifestation of this condition, which could be caused by transient ischaemia resulting from disturbed choroidal perfusion secondary to acute rise in intracranial pressure.

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p-NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1-H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment-evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.

Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium-induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N-acetyl-l-cysteine (NAC) inhibited chromium-induced activation of ATF6 and upregulation of PLK4. ATF6-specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium-induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS-ATF6-PLK4 pathway and provides molecular targets for inhibiting chromium-mediated CA, which may be useful for the assessment of CA in chromium-promoted tumorigenesis and cancer cell metastasis.

We investigate the Bloch bands and develop a linear response theory for nonlinear systems, where the interplay between topological parameters and nonlinearity leads to new band structures. The nonlinear system under consideration is described by the Qi-Wu-Zhang model with Kerr-type nonlinearity, which can be treated as a nonlinear version of Chern insulator. We explore the eigenenergies of the Hamiltonian and discuss its Bloch band structures as well as the condition of gap closing. A cone structure in the ground Bloch band and tubed structure in the excited Bloch band is found. We also numerically calculate the linear response of the nonlinear Chern insulator to external fields, finding that these new band structures break the condition of adiabatic evolution and make the linear response not quantized. This feature of response can be understood by examining the dynamics of the nonlinear system., 11 pages, 5 figures

Unidirectional reflectionlessness is investigated in a waveguide quantum electrodynamics system that consists of a cavity and a $\Lambda$-type three-level quantum dot coupled to a one-dimensional plasmonic waveguide. Analytical expressions of transmission and reflection coefficients are derived and discussed for both resonant and off-resonant couplings. By appropriately modulating the coupling strength, phase shift and Rabi frequency, unidirectional reflectionlessness is observed at the exceptional points. And unidirectional coherent perfect absorption is exhibited at the vicinity of exceptional point. These results might find applications in designing quantum devices of photons, such as optical switches and single-photon transistors., Comment: 11 pages, 7 figures

Yizhen Liu,1 Yumei Liu,2 Ping Zhao,3 Qunling Zhang,1 Xiaojian Liu,1 Fangfang Lv,1 Xiaonan Hong,1 Junning Cao,1 Kai Xue1,4 1Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 2Department of Endoscopy, Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Biology, University of North Alabama, Florence, AL 35632, USA; 4State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of ChinaCorrespondence: Kai XueDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, People’s Republic of ChinaTel +86 21 64175590Email xuekaishanghai@126.comBackground: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common subtype of extranodal non-Hodgkin lymphoma (NHL), with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as the commonly used treatment regimen. However, full cycles of standard R-CHOP present the risk of severe bleeding or perforation, even leading to emergency surgery, especially for those with deep lesions in their first 1– 2 cycles of treatment. This study aims to explore the safety and efficacy of fractioned R-CHOP (rituximab d0, 50% dose of CHOP d1 and d5) followed by standard R-CHOP cycles in PG-DLBCL patients guided by endoscopic ultrasonography (EUS).Patients and Methods: Thirty-one PG-DLBCL patients were analyzed in this retrospective study. All patients had lesions infiltrated to at least the 3rd layer of the stomach under EUS at baseline. Patients switched to standard R-CHOP if they showed the reduced infiltrated layers and restricted lesions after fractioned R-CHOP cycles.Results: The overall response rate, 5-year progression-free survival (PFS) and overall survival (OS) of patients in our study were 93.5%, 75% and 84%, respectively. No treatment delay or dosage reduction from gastric adverse event was observed. None of the patients in our study suffered from severe bleeding or perforation during the treatment. Kaplan–Meier analyses showed that PG-DLBCL patients characterized by multiple localization, lesions ≥ 3cm, having B symptoms, lower serum albumin level, and elevated LDH level were associated with worse PFS and OS.Conclusion: Our data indicate that it might be an effective approach in treating deeply infiltrated PG-DLBCL patients by switching fractioned R-CHOP to standard R-CHOP cycles guided by EUS.Keywords: primary gastric diffuse large B-cell lymphoma, endoscopic ultrasonography, R-CHOP, prognosis

Yi-Zhen Liu,1,* Pan Luo,2,* Cheng Liu,3 Kai Xue,1 Jia Jin,1 Zu-Guang Xia,1 Xiao-Jian Liu,1 Qun-Ling Zhang,1 Jun-Ning Cao,1 Xiao-Nan Hong,1 Fang-Fang Lv1 1Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 2Department of Medical Oncology, First People’s Hospital of Yueyang, Yueyang 414000, People’s Republic of China; 3Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang-Fang LvDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel +86 21 64175590Email lvff80@163.comObjective: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is relatively rare, and risk factors of this disease are still not well understood. This study aims to identify clinical features and prognostic factors of PT-DLBCL patients.Methods: Thirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed.Results: The median age of the patients was 57 (range 36–76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4–6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan–Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028).Conclusion: Our work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS.Keywords: primary testicular diffuse large B-cell lymphoma, clinical feature, prognosis

Kai Xue,1 Yi-Nan Wang,2 Xue Zhao,1 Hong-Xin Zhang,3 Dan Yu,1 Chun-Shun Jin11Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, People’s Republic of China; 2Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun 130041, People’s Republic of China; 3Changchun Institute of Optics, Fine Mechanics & Physics, Chinese Academy of Sciences, Changchun 130033, People’s Republic of ChinaPurpose: Tumor drug resistance limits the response to chemotherapy. Interestingly, sequential combination therapy enhances the anticancer efficacy of drugs like cisplatin (CDDP) via synergistic effects. We assayed the synergistic effects of combined photodynamic therapy programmed death receptor-ligand 1 (PDT) and chemotherapy in malignant Hep-2 cells.Methods: In the cultured Hep-2 cells, meta-tetra(hydroxyphenyl)chlorin (m-THPC) and CDDP were administered separately or in combination. The cellular viability and apoptosis were assessed, accompanied by measurement of the expression of Bax, Bcl-2, ATG-7, and LC3 (LC3-I and LC3-II). Additionally, nuclear chromatin changes, drug retention, and PD-L1 expression were further investigated following different treatments.Results: The sequential treatment significantly diminished cell viability and induced cell apoptosis, in consistency with the usage of single therapeutic strategies, as reflected by an increase in Bax expression and decrease of Bcl-2 expression. Moreover, ATG-7 and LC3-II/LC3-I ratio were reduced after administration of the sequential treatment. Synergetic effect of nuclear chromatin configuration, negative effects of cellular drug retention, and a decrease in PD-L1 expression were observed following the sequential treatment.Conclusion: The application of sequential treatment of PDT in combination with chemotherapy offers a promising therapeutic option for cancer treatment, by regulating the PD-L1 expression, autophagy, and non-mitochondrial pathways.Keywords: photodynamic therapy, sequential treatment, chemotherapy, PD-L1, Hep-2 cell

Zhenheng Wang,* Kaiwen Xue,* Maosheng Bai, Zhantao Deng, Jingjing Gan, Gang Zhou, Hongbo Qian,* Nirong Bao, Jianning Zhao Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs)-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis. Keywords: wear particles, gut microbiota, nanotoxicity, macrophage polarization, inflammatory cytokines, aseptic loosening

Residual char shows an obvious influence on ash fusibility through carbothermal reaction. Besides of SiO2, Fe2O3 can also react with residual char to produce metallic iron (Fe) and Fe3Si by Fe-char reaction at high temperatures. Effects of Fe2O3 content on fusibility and carbothermal reaction of ash with residual char were investigated in this work. The results showed that refractory mineral, metallic iron (Fe), Fe3Si and SiC, are formed by Fe-char reaction and carbothermal reaction between mineral and residual char. When Fe2O3 content of ash is lower than 12%, ash fusion temperatures (AFTs) of ash ascend with the increasing residual char content. However, when Fe2O3 content in ashes is more than 12%, flow temperature (FT) of ashes shows a decrease when residual char content increases from 10% to 15%. In the former case, residual char mainly engages in carbothermal reaction, and ash fusibility is largely dependent on SiC content which increases with the increasing residual char content. In the latter case, most of residual char is involved in Fe-char reaction. The AFTs of ashes largely depends on Fe3Si at high temperatures. An increase in Fe2O3 content is favorable to formation of Fe3Si. Besides, Fe2O3 in ash lowers temperature of carbothermal reaction from 1500 °C to 1300-1400 °C, while the increase of Fe2O3 content is detrimental to formation of SiC.

With the rapid development and wide application of computer, camera device, network and hardware technology, 3D object (or model) retrieval has attracted widespread attention and it has become a hot research topic in the computer vision domain. Deep learning features already available in 3D object retrieval have been proven to be better than the retrieval performance of hand-crafted features. However, most existing networks do not take into account the impact of multi-view image selection on network training, and the use of contrastive loss alone only forcing the same-class samples to be as close as possible. In this work, a novel solution named Multi-view Discrimination and Pairwise CNN (MDPCNN) for 3D object retrieval is proposed to tackle these issues. It can simultaneously input of multiple batches and multiple views by adding the Slice layer and the Concat layer. Furthermore, a highly discriminative network is obtained by training samples that are not easy to be classified by clustering. Lastly, we deploy the contrastive-center loss and contrastive loss as the optimization objective that has better intra-class compactness and inter-class separability. Large-scale experiments show that the proposed MDPCNN can achieve a significant performance over the state-of-the-art algorithms in 3D object retrieval.

Qunling Zhang,1,2 Junning Cao,1,2 Kai Xue,1,2 Xiaojian Liu,1,2 Dongmei Ji,1,2 Ye Guo,1,2 Xiaonan Hong1,2 1Department of Medical Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Abstract: Peripheral T cell lymphoma (PTCL) has a poor prognosis. Overexpression of vascular endothelial growth factor (VEGF) might contribute to the poor prognosis of PTCL and could be the target of novel therapy. The efficacy and safety of recombinant human endostatin (Endostar) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (ECHOP) have been explored in 15 PTCL patients. The objective response rate was 80%, with 53.3% patients having achieved complete response (CR) rate. The CR rate was 100% (3/3) in angioimmunoblastic T cell lymphoma (AITL) patients compared to only 36.4% (4/11) in PTCL not otherwise specified (PTCL-NOS) patients. With a median follow-up of 69 months, the 5-year progression-free survival and overall survival (OS) were 53% and 60%, respectively. The 5-year OS was 100% in AITL but was only 45% in PTCL-NOS. Seven out of 11 patients showed overexpression of VEGFR2 in their tumor vessels and had a better efficacy than those with low expression of VEGFR2. Grade 3 or 4 neutropenia is the most common toxicity observed. ECHOP was safe and might display potential benefit in AITL patients. Keywords: peripheral T cell lymphoma, recombinant human endostatin, VEGFR2, safety, efficacy, prognosis

Purpose Safe and reproducible delivery of gene therapy vector into the subretinal space is essential for successful targeting of the retinal pigment epithelium (RPE) and photoreceptors. The success of surgery is critical for the clinical efficacy of retinal gene therapy. Iatrogenic detachment of the degenerate (often adherent) retina in patients with hereditary retinal degenerations and small volume (eg, 0.1 ml) subretinal injections pose new surgical challenges. Methods Our subretinal gene therapy technique involved pre-operative planning with optical coherence tomography (OCT) and autofluorescence (AF) imaging, 23 G pars plana vitrectomy, internal limiting membrane staining with Membrane Blue Dual (DORC BV, Zuidland, Netherlands), a two-step subretinal injection using a 41 G Teflon tipped cannula (DORC) first with normal saline to create a parafoveal bleb followed by slow infusion of viral vector via the same self-sealing retinotomy. Surgical precision was further enhanced by intraoperative OCT (Zeiss Rescan 7000, Carl Zeiss Meditec AG, Jena, Germany). Foveal functional and structural recovery was evaluated using best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, microperimetry and OCT. Results Two patients with choroideremia aged 29 (P1) and 27 (P2) years, who had normal and symmetrical levels of best-corrected visual acuity (BCVA) in both eyes, underwent unilateral gene therapy with the fellow eye acting as internal control. The surgeries were uncomplicated in both cases with successful detachment of the macula by subretinal vector injection. Both treated eyes showed recovery of BCVA (P1: 76–77 letters; P2: 84–88 letters) and mean threshold sensitivity of the central macula (P1: 10.7–10.7 dB; P2: 14.2–14.1 dB) to baseline within a month. This was accompanied by normalisation of central retinal thickness on OCT. Conclusions Herein we describe a reliable technique for subretinal gene therapy, which is currently used in clinical trials to treat choroideremia using an adeno-associated viral (AAV) vector encoding the CHM gene. Strategies to minimise potential complications, such as avoidance of excessive retinal stretch, air bubbles within the injection system, reflux of viral vector and post-operative vitritis are discussed.

© 2017 International Society for Microbial Ecology All rights reserved. Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We also showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate.

Background MAIA microperimetry assesses macular sensitivity to projected point light sources and maps eye movements to assess fixation stability. While microperimetry is gaining prominence as an assessment tool in clinical and research settings, there is no consensus on whether it should be performed before or after pupil dilation. No studies to date have examined the effect of pupil dilation on results. The aim of this project was to elucidate the effect of pupil dilation on microperimetry outcomes. Design Prospective audit. Participants Twenty healthy patients from post-operative cataract clinic and ten patients with choroideremia to simulate a disease with peripheral visual field loss. Methods Subjects underwent 10-2 68 point field testing using the MAIA microperimeter on each eye. Subjects then underwentrandomised dilation of one eye and the test was repeated in both eyes. Main Outcome Measure We compared changes in threshold sensitivity and fixation stability pre- and post-pupil dilation. The undilated eye was analysed for any learning or fatigue effect caused by test repetition. Results Dilation produced no significant effect on threshold sensitivity (dilation effect: -0.29 decibels (dB), p=0.23) or fixation stability in healthy controls or in choroideremia patients (dilation effect: +0.08log bivariate contour ellipse area (BCEA) p = 0.14). There was also no significant learning effect seen in the undilated eye, with no improvement in threshold sensitivity (order of eye testing: +0.03logBCEA, p=0.71). Conclusions In the clinical setting patients may be tested for 10 degree microperimetry with or without pupil dilation, as both scenarios yield consistent and interchangeable results.

Heterosigma akashiwo (Hada) is a fragile, fish-killing alga. Efforts to understand and prevent blooms due to this harmful species to mitigate the impact on aquaculture require the development of methods for rapid and precise identification and quantification, so that adequate warning of a harmful algal bloom may be given. Here, we report the development and application of rRNA and rDNA-targeted oligonucleotide probes for fluorescence in situ hybridization (FISH) to aid in the detection and enumeration of H. akashiwo. The designed probes were species specific, showing no cross-reactivity with four common HAB causative species: Prorocentrum micans Ehrenberg, P. minimum (Pavillard) Schiller, Alexandrium tarmarense (Lebour) Balech, and Skeletonema costatum (Greville) Cleve, or with four other microalgae, including Gymnodinium sp. Stein, Platy-monas cordiformis (Karter) Korsch, Skeletonema sp.1 Greville and Skeletonema sp.2. The rRNA-targeted probe hybridized to cytoplasmic rRNA, showing strong green fluorescence throughout the whole cell, while cells labeled by rDNA-targeted probe exhibited exclusively fluorescent nucleus. The detection protocols were optimized and could be completed within an hour. For rRNA and rDNA probes, about a corresponding 80% and 70% of targeted cells could be identified and quantified during the whole growth circle, despite the inapparent variability in the average probe reactivity. The established FISH was proved promising for specific, rapid, precise, and quantitative detection of H. akashiwo. (C) 2008 Elsevier B.V. All rights reserved.

© 2015 IEEE. The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website.

MicroRNAs (miRs) are involved in tumorigenesis by regulating tumor suppressor genes and/or oncogenes. MiR187 was overexpressed in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and associated with high Ki67 expression, elevated lactate dehydrogenase, advanced International Prognostic Index and poor prognosis of patients. In vitro, ectopic expression of miR187 in T-lymphoma cell lines accelerated tumor cell proliferation, whereas treatment with miR187 inhibitor reduced cell growth. MiR187 downregulated tumor suppressor gene disabled homolog-2 (Dab2), decreased the interaction of Dab2 with adapter protein Grb2, resulting in Ras activation, phosphorylation/activation of extracellular signal-regulated kinase (ERK) and AKT, and subsequent stabilization of MYC oncoprotein. MiR187-overexpressing cells were resistant to chemotherapeutic agents like doxorubicin, cyclophosphamide, cisplatin and gemcitabine, but sensitive to the proteasome inhibitor bortezomib. Bortezomib inhibited T-lymphoma cell proliferation by downregulating miR187, dephosphorylating ERK and AKT and degrading MYC. In a murine xenograft model established with subcutaneous injection of Jurkat cells, bortezomib particularly retarded the growth of miR187-overexpressing tumors, consistent with the downregulation of miR187, Ki67 and MYC expression. Collectively, these findings indicated that miR187 was related to tumor progression in PTCL-NOS through modulating Ras-mediated ERK/AKT/MYC axis. Although potentially oncogenic, miR187 indicated the sensitivity of T-lymphoma cells to bortezomib. Cooperatively targeting ERK and AKT could be a promising clinical strategy in treating MYC-driven lymphoid malignancies.

Based on the RTT relation for a given rational $R$-matrix the {\em Yangian} and truncated {\em Yangian} are discussed. The former can be used to generate the long-range interaction models, whereas the latter can be related to the Goryachev-Chaplygin(GC) gyrostat. The trigonometric extension of the Goryachev-Chaplygin gyrostat has also been shown., Comment: Preprint ( reprint ) of Nankai Institute of Mathematics. For hard copy, write to Prof. Mo-lin GE, Nankai Institute of Mathematics. Do not send emails to this computer account

Dose-dependent inflammatory responses in adeno-associated virus (AAV)–mediated retinal gene therapy trials have restricted the use of high vector doses and impeded the ability to enhance therapeutic efficacy. Characterising the nature of this response, and devising methods to overcome it, are thus becoming increasingly important in the clinical application of gene therapies. In the experiments herein, I investigated the composition, timing, and magnitude of the cellular immune response to retinal gene therapy in mice using quantitative flow cytometric analysis. I observed a significant increase in retinal leukocytes from 14 days after subretinal injection of an AAV8 vector expressing green fluorescent protein (GFP). These consisted of a constant population of resident microglia and infiltrating peripheral leukocytes including macrophages, natural killer cells, CD4 and CD8 T cells, and natural killer T cells. An identical vector at an equivalent dose encoding a human therapeutic transgene elicited a diminished response compared to paired injections with a GFP vector. However, the proportions of the leukocyte populations remained similar, suggesting a common mechanism of immunity. In addition to the induction of a cell-mediated immune response, innate detection of AAV vectors may directly restrict transgene expression. Preliminary evidence suggested in vitro AAV transduction may be limited by the anti-viral nucleic acid sensors Toll-like receptor 9 and cyclic GMP AMP synthase, suggesting possible detection of transgenic AAV genomes. I also showed that the immunomodulatory drug hydroxychloroquine can significantly enhance AAV transduction in vitro, ex vivo, and in vivo, with indirect indication of the partial antagonism of TLR9. The lack of structural change in the retina following subretinal hydroxychloroquine delivery indicates that it could be a safe adjunct for improving retinal gene therapy efficacy.