Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry

Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but relatively little is known about early immunological change that proceeds from overt DN. Herein, this work aims to investigate the immune-driven pathogenesis of DN using mass cytometry (CyTOF). The peripheral blood mononuclear lymphocytes (PBMC) from 6 patients with early-stage nephropathy and 7 type II diabetes patients without nephropathy were employed in the CyTOF test. A panel that contains 38 lineage markers was designed to monitor immune protein levels in PBMC. The unsupervised clustering analysis was performed to profile the proportion of individual cells. t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the differences in DN patients’ immune phenotypes. Comprehensive immune profiling revealed substantial immune system alterations in the early onset of DN, including the significant decline of B cells and the marked increase of monocytes. The level of CXCR3 was dramatically reduced in the different immune cellular subsets. The CyTOF data classified the fine-grained differential immune cell subsets in the early stage of DN. Innovatively, we identified several significant changed T cells, B cell, and monocyte subgroups in the early-stage DN associated with several potential biomarkers for developing DN, such as CTLA-4, CXCR3, PD-1, CD39, CCR4, and HLA-DR. Correlation analysis further demonstrated the robust relationship between above immune cell biomarkers and clinical parameters in the DN patients. Therefore, we provided a convincible view of understanding the immune-driven early pathogenesis of DN. Our findings exhibited that patients with DN are more susceptible to immune system disorders. The classification of fine-grained immune cell subsets in this present research might provide novel targets for the immunotherapy of DN

淋毒性副睪丸炎ノ療法追加

Abstract We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities

Organization and evolution of climate responsive strategies, used in Turpan vernacular buildings in arid region of China

Under the global crisis of energy shortage and environmental pollution, the climate responsive strategies used in vernacular buildings have attracted much attention for their potential to reduce energy consumption and carbon emissions. However, the relationships between these traditional climatic strategies were not precisely perceived, which may cause the inapplicability of these strategies for contemporary rural houses. In this paper, taking the Turpan vernacular buildings in arid region of China, the climate responsive strategies of buildings in the most significant periods such as the Gaochang period (before 1318), the Khanate and Republican period (1318–1949), the Modern period (1949–2010), and the Contemporary period (2011–present) were summarized. In addition, two different types of climatic strategies organizations, namely multilayer spaces and integrated building envelopes, were identified based on the temperature difference measurement and comparative analysis. The assessment of thermal performance of the organizations was conducted by the methodology of software simulation. Furthermore, the applicability of the organizations in rural areas was discussed, and a new combined organization was proposed. Consequently, this study can contribute to provide the main approaches for climatically responsive rural houses

Detection and Analysis of Coastline and Landuse Change from 1960 to 2012 in Pearl River Delta, China

Coastline is the sea-land demarcation line in coastal regions. The position and shape of coastline depends on various natural and anthropogenic factors. The change of coastline exerts obvious influence on environment and economy in coastal regions. Therefore, it is important to detect and analysis the change of coastline and landuse for coastal environment and sustainable development. Pearl River Delta (PRD) is one of the most prosperous and fastest growing regions in China. The coastline and landuse in PRD have changed remarkably and continuously during the past decades. In this research, the change of coastline and landuse during 1960 to 2012 was detected with RS and GIS. Furthermore, coastline characteristics of temporal and spatial variation were analyzed with quantitative and spatial approach. And the relationship between the changes of coastline and landuse was explored. Therefore, the impact that urban expansion brought to landscape in coastal zone could be quantitatively analyzed. Finally, local government management on coastal wetland was discussed. The main outcomes of this research are summarized in the following points: (1) The length of coastline in PRD increased from 1134.95 km to 1508.02 km with annul increasing speed of 7.17km/a. Relatively, the coastline changed more obvious in three period (20042006, 2006-2008 and 2008-2010).The annual average change rate of coastline in the three period were -3.45%, 2.85% and 2.98%, respectively. After 2010, the speed of coastline change in PRD became lower. (2) The coastline had a greater increasing amount in the cities of Zhuhai, Guangzhou and Shenzhen, where the length of coastline increased 60.81%, 22.00%and 19.71%, respectively. (3) Nansha in Guangzhou, south Zhuhai and Qianhai in Shenzhen gained more newly-added land than any other area in PRD. Their land area increased from 172.34 km2 to 303.22 km2, 344.70 km2 to 603.29 km2 and 89.62 km2 to 145.49 km2, respectively. (4) In PRD, construction land expanded 33 times during 1960 to 2012. In the meanwhile, the area of forest and farm land decreased 47.53% and 56.70%, respectively. (5) The total area of newly-added land in PRD was 231.53km2, where farm land accounted for61.07%. From 1979 to 1990, the total area of newly-added land was 224.82 km2, where land for aquaculture accounted for 51.44%. From 1990 to 2000, the total area of newly-added land was 321.42km2, where farmland and land for aquaculture accounted 61.07%. It can be known that the land demand for agricultural development was the key factor that changed coastline in PRD before 2000. From 2000 to 2012, the total area of newly-added land was 100.34 km2, where construction land accounted for 51.30%. Since 2000, Land demand for urban construction has been the key factor that changed coastline in PRD. In conclusion, human activities, including agricultural development and urban construction, largely resulted in the significant change of coastline in PRD. (6) Establishment of the natural conservation area and construction of wetland park were found to be both effective ways to protect coastal wetland. Otherwise it will gradually disappear under rapid process of urbanization

Pt(II) bipyridyl complexes bearing substituted fluorenyl motif on the bipyridyl and acetylide ligands: Synthesis, photophysics, and reverse saturable absorption

A series of Pt(II) diimine complexes bearing benzothiazolylfluorenyl (BTZ-F8), diphenylaminofluorenyl (NPh2- F8), or naphthalimidylfluorenyl (NI-F8) motifs on the bipyridyl or acetylide ligands (Pt-4−Pt-8), (i.e., {4,4′-bis[7-R1-F8-(≡)n-]bpy}Pt(7- R2-F8- ≡ -)2, where F8 = 9,9′-di(2-ethylhexyl)fluorene, bpy = 2,2′- bipyridine, Pt-4: R1 = R2 = BTZ, n = 0; Pt-5: R1 = BTZ, R2 = NI, n = 0; Pt-6: R1 = R2 = BTZ, n = 1; Pt-7: R1 = BTZ, R2 = NPh2, n = 1; Pt- 8: R1 = NPh2, R2 = BTZ, n = 1) were synthesized. Their ground-state and excited-state properties and reverse saturable absorption performances were systematically investigated. The influence of these motifs on the photophysics of the complexes was investigated by spectroscopic methods and simulated by time-dependent density functional theory (TDDFT). The intense absorption bands below 410 nm for these complexes is assigned to predominantly 1π,π* transitions localized on either the bipyridine or the acetylide ligands; while the broad low-energy absorption bands between 420 and 575 nm are attributed to essentially 1MLCT (metal-to-ligand charge transfer)/ 1LLCT (ligand-to-ligand charge transfer) transitions, likely mixed with some 1ILCT (intraligand charge transfer) transition for Pt-4−Pt-7, and predominantly 1ILCT transition admixing with minor 1MLCT/1LLCT characters for Pt-8. The different substituents on the acetylide and bipyridyl ligands, and the degrees of π-conjugation in the bipyridyl ligand influence both the 1π,π* and charge transfer transitions pronouncedly. All complexes are emissive at room temperature. Upon excitation at their respective absorption band maxima, Pt-4, Pt-6, and Pt-8 exhibit acetylide ligand localized 1π,π* fluorescence and 3MLCT/3LLCT phosphorescence in CH2Cl2, while Pt-5 manifests 1ILCT fluorescence and 3ILCT phosphorescence. However, only 1LLCT fluorescence was observed for Pt-7 at room temperature. The nanosecond transient absorption study was carried out for Pt-4−Pt-8 in CH3CN. Except for Pt-7 that contains NPh2 at the acetylide ligands, Pt-4−Pt-6 and Pt-8 all exhibit weak to moderate excited-state absorption in the visible spectral region. Reverse saturable absorption (RSA) of these complexes was demonstrated at 532 nm using 4.1 ns laser pulses in a 2 mm cuvette. The strength of RSA follows this trend: Pt-4 > Pt-5 > Pt-7 > Pt-6 > Pt-8. Incorporation of electron-donating substituent NPh2 on the bipyridyl ligand significantly decreases the RSA, while shorter π-conjugation in the bipyridyl ligand increases the RSA. Therefore, the substituent at either the acetylide ligands or the bipyridyl ligand could affect the singlet and triplet excited-state characteristics significantly, which strongly influences the RSA efficiency

A strategy for antioxidant quality evaluation of Aster yunnanensis based on fingerprint-activity relationship modeling and chemometric analysis

In this study, a fingerprint-activity relationship between ultrahigh performance liquid chromatography (UHPLC) fingerprints and antioxidant activity was established to evaluate the quality of Aster yunnanensis Franch.(AYF) from different collecting spots. First, the fingerprint of AYF was established by UHPLC, and the similarity analysis was analyzed based on twenty-one common peaks. Then the chemical constituents from AYF were analyzed and identified by UHPLC-quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS). Next, the antioxidant activity of twelve batches of AYF was assessed in vitro. Subsequently, eleven chemical markers were screened out by fingerprints and antioxidant activity utilizing grey relational analysis (GRA) and partial least squares (PLS). Finally, the contents of eleven chemical markers in twelve batches of AYF were detected by UHPLC, and the antioxidant quality of AYF was evaluated using chemometric analysis, such as principal components analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS). The results showed that the antioxidant efficacy was associated with the total content of eleven compounds of AYF. Moreover, this method to discover quality markers was reasonable by fingerprint-activity relationship combination with chemometric analysis. The present study will certify quality markers associated with therapeutic effects, and provide a powerful strategy for evaluating the resource quality of AYF

Integrative analysis of miRNA–mRNA network in idiopathic membranous nephropathy by bioinformatics analysis

Background Currently, several specific antigens, M-type receptor for secretory phospholipase A2(PLA2R1), thrombospondin type-1 domain-containing 7A(THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1), are discovered associated with the onset of idiopathic membranous nephropathy (IMN). But the pathomechanisms of IMN still need to be further claried. Understanding the mechanisms of IMN is required to improve its diagnosis and treatment. Methods In this study, we constructed miRNA regulatory networks to investigate IMN development. Moreover, miRNAs and mRNAs that were differentially expressed between Idiopathic Membranous Nephropathy (IMN) patients and normal controls were examined using the GSE115857 dataset and our previous sequence study. DE miRNA target genes were determined based on the FUNRICH software, starBase, miRDB, and miRWalk, and an miRNA-mRNA network was designed using DE-mRNAs that were negatively correlated with DE-miRNAs. The miRNA-mRNA network contained 228 miRNA-mRNA pairs. Thereafter, we conducted KEGG pathway, GO functional annotation, immune-related gene screening, protein interaction networks, and potential hub gene analyses. Furthermore, 10 miRNAs and 10 genes were determined and preliminarily validated using the validation dataset from GEO. Finally, we identified which pair may offer more accurate diagnosis and therapeutic targets for IMN. Results Two miRNA-mRNA pairs, miR-155-5p-FOS and miR-146a-5p-BTG2, were differentially expressed in IMN, indicating that these genes may affect IMN through immune processes. These findings may offer more accurate diagnoses and therapeutic targets for IMN