Interferon beta(IFN-β) treatment exerts potential neuroprotective effects through neurotrophic factors and novel neurotensin/neurotensin high affinity receptor 1 pathway

Multiple sclerosis（MS）is a chronic autoimmune disease of the central nervous system（CNS）characterized by coexisting processes of inflammation,demyelination,axonal neurodegeneration,and gliosis.It is the most common disabling neurological disease in young adulthood.

Isolation and cloning of the gene encoding high affinity phosphate transporter in rice

High affinity phosphate transporterplays an important role in plantadapting to low phosphorus. Isolationof genes coding this kind of proteinhas attracted worldwide scholars toaccomplish. We aimed to isolate thegene and transfer it to target plants

pFTAA: a high affinity oligothiophene probe that detects filamentous tau in vivo and in cultured neurons

Tauopathies describe a group of neurodegenerative diseases in which the protein tau,encoded by the gene MAPT,is aberrantly misfolded,leading to tau aggregation,neural dysfunction,and cell death（Spillantini and Goedert,2013）.In Alzheimer＇s disease（AD）,tau forms the characteristic intracellular neurofibrillary tangles（NFTs）,which are thought to be the major cause of neurodegeneration（Bloom,2014）.In other tauopathies,including frontotemporal dementia with Parkinsonism linked to chromo- some 17 （FTDP-17T）, corticobasal degeneration and progressive supranuclear palsy, there are specific forms of tau aggregates and filaments without any amyloid pathology, demonstrating tau＇s po- tent disease-causing potential （Spillantini and Goedert, 2013）. Tau is a microtubule （MT） binding protein, which becomes abnormally hyperphosphorylated on several residues prior/during the process of aggregation, thereby causing loss of its MT binding activity （Mandelkow and Mandelkow, 2012）.

High Performance Affinity Chromatography of Antithrombin III Based on Monodisperse Poly (glycidyl methacrylate) Beads

A new approach for the separation of antithrombin III with high performance affinity chromatography (HPAC) was described. A novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were used as the affinity support. With the water-soluble carbodiimide, heparin was linked covalently to amino-PGMA-beads, which was prepared by amination of PGMA. The adsorbent obtained exhibits high binding activity to antithrombin III (ATIII), good resolution and excellent mechanical properties and can be used under high flow rate.

Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy

Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells.In this complex structure,cells cross-talk and interact,thus jointly promoting cancer development and metastasis.Recently,immunoregulatory molecule-based cancer immunotherapy has greatly improved treatment efficacy for solid cancers,thus enabling some patients to achieve persistent responses or cure.However,owing to the development of drug-resistance and the low response rate,immunotherapy against the available targets PD-1/PD-L1 or CTLA-4 has limited benefits.Although combination therapies have been proposed to enhance the response rate,severe adverse effects are observed.Thus,alternative immune checkpoints must be identified.The SIGLECs are a family of immunoregulatory receptors(known as glyco-immune checkpoints)discovered in recent years.This review systematically describes the molecular characteristics of the SIGLECs,and discusses recent progress in areas including synthetic ligands,monoclonal antibody inhibitors,and Chimeric antigen receptor T(CAR-T)cells,with a focus on available strategies for blocking the sialylated glycan-SIGLEC axis.Targeting glyco-immune checkpoints can expand the scope of immune checkpoints and provide multiple options for new drug development.

History of the dopamine hypothesis of antipsychotic action

The dopamine hypothesis of how antipsychotic drugs exert their beneficial effect in psychotic illness has an interesting history that dates back to 1950.This hypothesis is not to be confused with the dopamine hypothesis of schizophrenia;the aim of the latter is to explain the etiology of schizophrenia.The present review does not deal with schizophrenia but,rather,with the historical development of our current understanding of the dopamine-associated actions of the drugs that reduce the symptoms of psychosis.This historical review begins with the serendipitous discovery of chlorpromazine,a drug synthesized around a chemical core that initially served to produce man-made dyes.This molecular core subsequently contributed to the chemistry of antihistamines.It was with the aim of producing a superior antihistamine that chlorpromazine was synthesized;instead,it revolutionized the treatment of psychosis.The first hypothesis of how this drug worked was that it induced hypothermia,a cooling of the body that led to a tranquilization of the mind.The new,at the time,discoveries of the presence of chemical transmitters in the brain soon steered investigations away from a temperature-related hypothesis toward questioning how this drug,and other drugs with similar properties and effects,modulated endogenous neurotransmission.As a result,over the years,researchers from around the world have begun to progressively learn what antipsychotic drugs do in the brain.

Optical coherence tomography and T cell gene expression analysis in patients with benign multiple sclerosis

Benign multiple sclerosis is a retrospective diagnosis based primarily on a lack of motor symptom progression. Recent findings that suggest patients with benign multiple sclerosis experience non-motor symptoms highlight the need for a more prospective means to diagnose benign multiple sclerosis early in order to help direct patient care. In this study, we present optical coherence tomography and T cell neurotrophin gene analysis findings in a small number of patients with benign multiple sclerosis. Our results demonstrated that retinal nerve fiber layer was mildly thinned, and T cells had a distinct gene expression profile that included upregulation of interleukin 10 and leukemia inhibitory factor, downregulation of interleukin 6 and neurotensin high affinity receptor 1（a novel neurotrophin receptor）. These findings add evidence for further investigation into optical coherence tomography and m RNA profiling in larger cohorts as a potential means to diagnose benign multiple sclerosis in a more prospective manner.

Air-stable ambipolar organic field effect transistors with heterojunction of pentacene and N,N'-bis(4-trifluoromethylben-zyl) perylene-3,4,9,10-tetracarboxylic diimide

Fabrication of ambipolar organic field-effect transistors （OFETs） is essential for the achievement of an organic complementary logic circuit. Ambipolar transports in OFETs with heterojunction structures are realized.We select pentacene as a P-type material and N,N＇-bis（4-trifluoromethylben-zyl）perylene-3,4,9,10-tetracarboxylic diimide （PTCDI-TFB） as a n-type material in the active layer of the OFETs.The field-effect transistor shows highly air-stable ambipolar characteristics with a field-effect hole mobility of 0.18 cm^2/（V·s） and field-effect electron mobility of 0.031 cm^2/（V·s）.Furthermore the mobility only slightly decreases after being exposed to air and remains stable even for exposure to air for more than 60 days.The high electron affinity of PTCDI-TFB and the octadecyltrichlorosilane （OTS） self-assembly monolayer between the SiO2 gate dielectric and the organic active layer result in the observed air-stable characteristics of OFETs with high mobility.The results demonstrate that using the OTS as a modified gate insulator layer and using high electron affinity semiconductor materials are two effective methods to fabricate OFETs with air-stable characteristics and high mobility.

Evaluation of a water-soluble adjuvant for the development of monoclonal antibodies against small-molecule compounds

A water-soluble adjuvant named QuickAntibody （QA） was introduced into the procedure of mouse immunization for the development of hapten-specific monoclonal antibodies （mAbs）, using four kinds of pesticides as model compounds. Compared with conventional Freund＇s adjuvants, QA treatments offered relatively low but acceptable antiserum titers after three inoculations, gave little adverse effects to the experimental animals, and were preferable in harvesting splenocytes during the steps of cell fusion. Afterwards, hybridomas from the QA group were prepared and screened by both non-competitive and competitive indirect enzyme-linked immunosorbent assays （ELISAs）. The efficiency of gaining immune-positive hybridomas was satisfactory, and the resultant mAbs showed sensitivities （half maximal inhibitory concentration （IC50）） of 0.91, 2.46, 3.72, and 6.22 ng/ml to triazophos, parathion, chlorpyrifos, and fenpropathrin, respectively. Additionally, the performance of QA adjuvant was further confirmed by acquiring a high-affinity mAb against okadaic acid （IC50 of 0.36 ng/ml） after three immunizations. These newly developed mAbs showed similar or even better sensitivities compared with previously reported mAbs specific to the corresponding analytes. This study suggested that the easy-to-use adjuvant could be applicable to the efficient gen- eration of highly sensitive mAbs against small compounds.

Discovery of naphthalimide conjugates as fluorescent probes for α_1-adrenoceptors

α1-Adrenoceptors（α1-ARs）, including at least three subtypes, α（1A）, α（1B） and α（1D）, which play essential roles in G protein-coupled receptors（GPCRs）, can convey multiple pivotal extracellular signals in varied tissues and organs. In this research, a series of napthalimide-based small-molecule fluorescent probes（1a-1f） for α1-ARs, including two parts, a pharmacophore（quinazoline and phenylpiperazine） for α1-AR recognition and a fluorophore（naphthalimide） for visualization, were designed and synthesized successfully. These compounds display excellent fluorescence property and high affinity to receptors,which were used successfully for in vitro visualization of α1-adrenoceptors.

Visualization of α_1-adrenergic receptors with phenylpiperazine-based fluorescent probes

Several novel fluorescent probes targeting α_1-adrenergic receptors were well designed and synthesized by conjugating phenylpiperazine pharmacophore with coumarin and fluorescein fluorophores. These compounds showed suitable fluorescence property, high receptor affinity, and low cytotoxicity. Moreover, the cell imaging results displayed that these probes can be effective tools for the real-time detection of ligand-receptor interactions, as well as the visualization and location of α_1-adrenergic receptors in living cells.

Synthesis and characterization of novel conjugated polymers based on 3-cyclobutene-l,2-dione moiety

Three novel conjugated polymers bearing 3,4-bis（4-hexylthiophen-2-yl）-3-cyclobutene-1,2-dione unit in their main chain have been synthesized successfully in good yields through Suzuki or Stille coupling reaction.Their molecular structures have been confirmed by FT-IR,~1H NMR and ^（13）C NMR.All these copolymers exhibit broad and strong absorption bands in UV-vis region,and their optical band gaps are calculated to be 1.6-2.0 eV.suggesting that they have good coverage with the solar spectrum.These polymers have good thermostability and solubility in common organic solvents.Moreover,all these objective macromolecules possess high electron affinity of～3.8 eV determined from cyclic voltammetry measurement,implying that they are potential n-type polymeric photovoltaic materials.