DIGITAL SEARCH ADVERTISING – THE ROLE OF POST-CLICK FACTORS IN GENERATING PURCHASE CONVERSIONS

A lot of research is available on the effectiveness of search as an advertising channel. Most of these studies tend to treat a click on a search ad as a binary event. All of them study the events leading to the click. This paper goes beyond this to study the post click actions taken by a user subsequent to clicking on a search ad, and refers to those actions as depth of interaction, and testing the variables that have an effect on the nal outcome. We use a prescriptive research design employing binary logistic regression analysis. Results indicate that the duration of time spent, device used, and recency of visit have a very high positive effect on the nal outcome.

Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery

The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry / 浙江大学学报·医学版

OBJECTIVES@#To design and prepare silk fibroin/hyaluronic acid composite hydrogel.@*METHODS@#The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope.@*RESULTS@#The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good.@*CONCLUSIONS@#The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

Bioorthogonal click-to-release reaction for regulating iodo-BODIPY PDT probe / 药学学报

In this study, we synthesized six tetrazine-dipyrromethene boron difluoride (BODIPY) probes and achieved a remarkable up to 14-fold increase in singlet oxygen yield via tetrazine bioorthogonal click-to-release reactions. We systematically investigated the photodynamic activity of these probes, revealing crucial structure-activity relationships. Additionally, we evaluated the stability and release kinetics of these probes and identified P5 and P6 as ideal candidates for photodynamic therapy in live cells. This innovative strategy opens new avenues for fine-tuning the photodynamic properties of BODIPY dyes, thereby expanding their utility in cancer therapy.

Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

Pretargeted immunoPET imaging with epidermal growth factor receptor monoclonal antibody in mouse models / 中华核医学与分子影像杂志

Objective:To explore the feasibility of pretargeting technique for immunoPET with epidermal growth factor receptor (EGFR) monoclonal antibody in EGFR positive/negative tumor bearing mice.Methods:Cetuximab- Trans-cyclooctene (TCO)was obtained by modifying Cetuximab with TCO- N-hydroxysuccinimide (NHS). 2, 2′-((6-amino-1-(4, 7-bis-(carboxymethyl)-1, 4, 7-triazonan-1-yl)hexan-2-yl)azanediyl)-diacetic acid (L-NETA)was used as a chelating agent to prepare the radioligand 68Ga-L-NETA-tetrazine (Tz), then the labeling rate and in vitro stability of the product were determined. Human basal breast cancer cells MDA-MB-468 (EGFR+ ) and MDA-MB-231 (EGFR-) were cultured in vitro. In vitro experiments were performed to explore the specificity of the probe and the feasibility of pretargeting technique. Nude mice (Balb/c-nu) bearing xenografts of the above two cell lines were established. Cetuximab-TCO (50 μg) was injected into the tumor-bearing mice in advance, then 68Ga-L-NETA-Tz was injected at different time points (48, 36, 24 and 12 h), and pretargeting was realized through " click chemistry" . Small-animal PET imaging and biodistribution were performed to evaluate pharmacokinetic properties and specificity of the probe. The one-way analysis of variance was used to compare the data. Results:The 68Ga-L-NETA-Tz molecular probe was successfully prepared with the labeling yield >95%, and the radiochemical purity was >95% after 2 h. Cetuximab-TCO and 68Ga-L-NETA-Tz were added to MDA-MB-468 cells successively, and the cell uptake rate reached (0.69±0.04)% at 1 h, which demonstrated the feasibility of the pretargeting technique. PET imaging and biodistribution results showed that the best imaging results were obtained in 36 h pre-injection group, in which the tumor uptake was the highest ((0.77±0.05) percentage activity of injection dose per gram of tissue (%ID/g), 1 h) and the tumor/muscle ratio was optimal (4.67±0.46); the tumor uptake in the blocking group, the group without injecting Cetuximab-TCO, and the MDA-MB-231 group were significantly lower ((0.35±0.01), (0.39±0.05), (0.45±0.10) %ID/g; F=15.50, P=0.002). Conclusions:EGFR targeted immunoPET imaging is successfully performed in mouse models of breast cancer by injecting Cetuximab-TCO and 68Ga-L-NETA-Tz successively. It provides an effective method for immunoPET imaging of monoclonal antibodies.

Preparation of 68Ga labeled pre-targeted molecular probe based on bio-orthogonal Diels-Alder click chemistry and CD11b receptor targeted imaging in CT26 colon cancer mouse models / 中华核医学与分子影像杂志

Objective:To prepare a 68Ga labeled probe targeting integrin alpha M(CD11b) receptor, namely 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-Glycine-Arginine-Glutamate-Arginine-Glutamate-polyethylene glycol 11-1, 2, 4, 5-terazine/CD11b antibody-F(ab′) 2-trans-cyclooctene ( 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO), and to explore its feasibility as a molecular probe for CD11b receptor through microPET imaging. Methods:Immunofluorescence was used to detect the expression of CD11b on the surface of RAW264.7 cell. CD11b specific monoclonal antibody (M1/70) was conjugated with TCO, and anti-CD11b-F(ab′) 2-TCO fragment was obtained. The ligand NOTA-Polypeptide-PEG 11-Tz was labeled with 68Ga, and its specific activity and radiochemical purity were detected. Pre-targeted cell binding experiment was conducted to evaluate the binding ability of molecular probe. CT26 colon cancer bearing mouse models were established, and then pre-targeted biodistribution and imaging experiments were performed. Immunohistochemical experiment was used to verify the expression of CD11b receptor in tumor. The one-way analysis of variance was used to compare the data. Results:The results of immunofluorescence demonstrated CD11b receptor was highly expressed on the surface of RAW264.7 cell. Anti-CD11b-F(ab′) 2-TCO fragment was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). 68Ga-NOTA-Polypeptide-PEG 11-Tz was successfully synthesized, with the labeling efficiency of 94.6%. The specific activity was 7.0-7.4 MBq/μg, and the radiochemical purity was higher than 95%. Pre-targeted cell binding experiment confirmed that the molecular probe bound to the CD11b receptor. The biodistribution and imaging experiments showed that the kidney radioactivity uptake was high at pre-targeted 4, 12 and 24 h intervals, which proved that probe was excreted through the urinary system. In addition, molecular probe had higher radioactive uptake at the tumor site, with the tumor/muscle ratios of 9.23±1.45, 12.53±1.36 and 10.74±1.11 ( F=848.8, P<0.05). When the radioligand was injected 1 h after the pre-positioned 12 h interval, the images contrast was the best, with the standardized uptake value (SUV) in tumor and muscle of 0.67±0.12, 0.09±0.04, respectively. Immunohistochemistry verified the highly expression of CD11b receptor in tumor. Conclusions:The pre-targeted molecular probe 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO is successfully synthesized. The molecular probe has targeting ability for CD11b + colon cancer, and is expected to be used as a tracer targeting CD11b receptor in vivo.

Quinolinotriazole antiplasmodials via click chemistry: synthesis and in vitro studies of 7-Chloroquinoline-based compounds

Malaria is nowadays one of the most serious health concerns in a global scale and, although there is an evident increase in research studies in this area, pointed by the vast number of hits and leads, it still appears as a recurrent topic every year due to the drug resistance shown by the parasite exposing the urgent need to develop new antimalarial medications. In this work, 38 molecules were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) or "click" chemistry, following different routes to produce 2 different organic azides, obtained from a 4,7 dicholoquinoline, reacted with 19 different commercially available terminal alkynes. All those new compounds were evaluated for their in vitro activity against the chloroquine resistant malaria parasite Plasmodium falciparum (W2). The cytotoxicity evaluation was accomplished using Hep G2 cells and SI index was calculated for every molecule. Some of the quinoline derivatives have shown high antimalarial activity, with IC50 values in the range of 1.72-8.66 µM, low cytotoxicity, with CC50>1000 µM and selectivity index (SI) in the range of 20-100, with some compounds showing SI>800. Therefore, the quinolinotriazole hybrids could be considered a very important step on the development of new antimalarial drugs

Tetrazine bioorthogonal click-to-release reaction for releasing peptides / 药学学报

This paper aimed to investigate the release efficiency of peptide at carbon terminal triggered by tetrazine bioorthogonal click-to-release reaction, and further explored the potential application of this reaction in functional modification and mild cleavage in solid-phase peptide synthesis. Thirteen peptide derivatives modified by trans-cyclooctene (TCO) were designed and synthesized, which were reacted with tetrazine to release the peptides. The results showed that the release rates of peptide were 90.0% to 97.7% in one hour. The strategy has good compatibility with the functional side-groups and the length of peptides, which expands the applications scope of tetrazine bioorthogonal click-to-release reaction. At the same time, a novel bifunctional trans-cyclooctene molecule was designed and synthesized. The active peptide GIRLRG was modified by fluorophore on the solid-phase resin, and released through tetrazine click-to-release reaction under mild condition, providing a new strategy for the solid-phase modification and release strategy of the peptide.

Respuestas evocadas auditivas obtenidas mediante un estímulo chirp de banda ancha / Auditory evoked responses obtained by a broad-band chirp stimulus

Introducción: La estimación de la audición con Potenciales Evocados Auditivos de Tallo Cerebral obtenidos mediante estímulos tipo chirp constituye una alternativa de reciente aplicación. Varios autores han demostrado que, este tipo de estimulación compensa el retardo de la onda sonora en la codificación de frecuencias, generándose Potenciales Evocados Auditivos de Tallo Cerebral con componentes de amplitudes mayores. Objetivos: Diseñar y generar un estímulo chirp (banda ancha) para implementar en el sistema AUDIX (La Habana, Neuronic SA) y, realizar una serie de controles para evaluar su viabilidad en el registro de Potenciales Evocados Auditivos de Tallo Cerebral en sujetos con audición normal. Métodos: Las formulaciones que se utilizaron en la generación del estímulo fueron implementadas como una función en Matlab®, y luego, insertada en el sistema AUDIX con las siguientes especificaciones técnicas, frecuencia de muestreo: 48 kHz, composición de frecuencias (ascendente): 350-11300 Hz, y duración total: 4,95 ms. Se obtuvieron registros de PEATC mediante estímulos chirp y click a un nivel de intensidad fija (60 dB nHL) en 9 sujetos adultos (18 oídos) con audición normal. Resultados: El estímulo chirp diseñado tuvo un comportamiento funcional similar a lo reportado en la literatura. Cuando se compara con los Potenciales Evocados Auditivos de Tallo Cerebral -click, la onda V de Potenciales Evocados Auditivos de Tallo Cerebral -chirp mostró valores de amplitud significativamente mayores (relación de amplitud chirp/click: 1,62), con una ganancia promedio de 54 por ciento (p< 0,001, n= 18, prueba de rangos de Wilcoxon). Conclusiones: El estímulo chirp (banda ancha) diseñado resulta más eficiente que el estímulo click para obtener registros de Potenciales Evocados Auditivos de Tallo Cerebral. Con respecto a la amplitud de la onda V, el sistema muestra un funcionamiento lineal (mejor sincronía neural). Este tipo de estimulación pudiera resultar de mucha utilidad en programas de pesquisa auditiva neonatal pues la obtención de una onda V de mayor amplitud permitiría su fácil y rápida detección, y posible automatización(AU)

Introduction: Estimation of audition through brainstem auditory evoked potentials obtained by chirp stimuli is an alternative of recent application. It has been shown by several authors that this type of stimulation compensates for retardation of the sound wave in the coding of frequencies, generating auditory evoked responses with components of higher amplitudes. Objectives: Design and develop a broad-band chirp stimulus to be implemented in the AUDIX system and conduct a control series evaluation of its viability to register brainstem auditory evoked potentials in normal-hearing subjects. Methods: The formulations used to generate the stimulus were implemented as a function on Matlab® and then incorporated into the AUDIX system with the following technical specifications: sampling frequency: 48 kHz, frequency composition (rising): 350-11 300 Hz, and total duration: 4.95 ms. BAEP registries were obtained with chirp and click stimuli at a fixed intensity level (60 dB nHL) in nine normal-hearing adult subjects (18 ears). Results: The chirp stimulus designed had a functional behavior similar to the one reported in the literature. When compared with the click-BAEP, the V wave of chirp-BAEP displayed significantly higher amplitude values (chirp/click amplitude ratio: 1.62), with an average gain of 54 percent (p< 0.001, n= 18, Wilcoxon rank test). Conclusions: The broad band chirp stimulus designed proved to be more efficient than the click stimulus to obtain registries of Brainstem Auditory Evoked Potentials. Regarding V wave amplitude, the system was found to function linearly (better neural synchrony). This type of stimulation could be very useful in neonatal hearing screening programs, since a higher amplitude V wave could facilitate its fast and easy detection and possible automation(AU)

Applicatoin progress on click chemistry in targets identification of bioactive components from Chinese materia medica / 中草药

The target is the basis for the active ingredients of Chinese materia medica (CMM), which plays an important role in the patients’ body. Target identification is the key work for the development of CMM. However, the current studies on the target of CMM are still limited, and it has become a bottleneck in the modernization of CMM. Therefore, new ideas and new technologies are required for the research on targets. Recently, a new method for the study of targets has been provided by the technology of activity-based protein profiling represented by click chemistry. The application of click chemistry in target identification of CMM in recent years is briefly reviewed and summarized, and the trends of application and development of click chemistry are prospected in this review.

New species of Elateridae (Coleoptera) from Madre de Dios, Peru, with new taxonomic changes and distribution records / Especies nuevas de Elateridae (Coleoptera) de Madre de Dios, Perú, con nuevos cambios taxonómicos y registros de distribución

The Elateridae fauna of Peru is updated with species new to science, new country records and new taxonomic combinations from the Madre de Dios region. Ten species representing eight genera are described as new: Conoderus wachiperi new species (Agrypninae, Oophorini) Cosmesus aca new species (Elaterinae, Pomachilini), Dipropus amarakaeri new species and Dipropus losamigos new species (Elaterinae, Ampedini, Dicrepidiina), Esthesopus machiguenga new species (Cardiophorinae), Glyphonyx peruanus new species (Elaterinae, Adrastini), Lissomus carmen new species (Lissominae), Paradonus kosnipata new species (Negastriinae), and Pomachilius qusqu new species and Pomachilius wayqecha new species (Elaterinae, Pomachilini). Aeolus platynotus Candèze is changed to Conoderus platynotus (Candèze) new combination and Aeolus ticuna Johnson is changed to Conoderus ticuna (Johnson) new combination (Agrypninae, Oophorini); and Crigmus brunnipilis (Candèze) is changed to Probothrium brunnipilis (Candèze) new combination (Elaterinae, Elaterini). Twenty-seven (27) species, the genera Glyphonyx Candèze and Paradonus Stibick, the tribe Adrastini, and the subfamily Negastriinae are added to the Peru faunal list. There are now 201 species representing 48 genera and 9 subfamilies recorded from Peru.

La fauna Elateridae del Perú se actualiza con especies nuevas para la ciencia, nuevos registros de países y nuevas combinacion es taxonómicas de la región de Madre de Dios. Diez especies que representan ocho géneros se describen como nuevas: Conoderus wachiperi nueva especie, Cosmesus aca nueva especie, Dipropus amarakaeri nueva especies, Dipropus losamigos, nueva especie, Esthesopus machiguenga nueva especie, Glyphonyx peruanus nueva especie, Lissomus carmen nueva especie, Paradonus kosnipata nueva especie, Pomachilius qusqu nueva especie, Pomachilius wayqecha nueva especie. Aeolus ticuna Johnson se cambia a Conoderus ticuna (Johnson) nueva combinación, Aeolus platynotus Candèze se cambia a Conoderus platynotus (Candèze) nueva combinación, y Crigmus brunnipilis (Candèze) se cambia a Probothrium brunnipilis (Candèze). Veintisiete (27) especies, los géneros Glyphonyx Candèze y Paradonus Stibick, la tribu Adrastini y la subfamilia Negastriinae se agregan a la lista de fauna de Perú. Ahora hay 201 especies que representan 48 géneros y 9 subfamilias se registran en el Perú.

Click Chemistry-Based Injectable Hydrogels and Bioprinting Inks for Tissue Engineering Applications

BACKGROUND: The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state. METHODS: In this review, we present the recent developments of in situ hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels–Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions. RESULTS: The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and in situ injectable forms. CONCLUSION: Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in in situ 3D bioprinting for tissue or organ regeneration.

The clinical effects of upper articular cavity injection with hyaluronate combined with Twin-block in the treatment of temporomandibular joint clicks / 实用口腔医学杂志

Objective: To observe the clinical effects of upper articular cavity injection with hyaluronate(HA) combined with Twinblock in the treatment of temporomandibular joint(TMJ) clicks. Methods: 60 patients with TMJ clicks were divided into 3 groups(n = 20) and were treated by articular cavity injection combined with Twin-block(group 1),Twin-block only(group 2) and injection of sodium hyaluronate gel(group 3) respectively. The effects were evaluated and compared before and after treatment by both doctors and patients. Results: The effective rate of group 1,2 and 3 was 95％,and 65％ respectively(P ＜ 0. 05). After treatment the TMJ clicks were almost dispeared in group 1,remitted in group 2 and slightly remitted in group 3. Conclusion: The articular cavity injection of HA combined with Twin-block is more effective in the treatment of TMJ clicks than Twin-block or articular cavity injection of HA.

Beetles of Peru: a survey of the Families. Eucnemidae Eschscholtz, 1829

A checklist of the eucnemid beetles of Peru is presented, based on a literature survey and identification of specimens from two museums. The Peruvian fauna comprises ~107 species in 30 genera from eight tribes and three subfamilies. Nine genera are newly recorded for Peru. They include: Xylophilus Mannerheim 1823, Temnillus Bonvouloir 1871, Gastraulacus Guérin-Méneville 1843, Somahenecus Cobos 1964, Silveriola Cobos 1956, Onichodon Newman 1838, Cladus Bonvouloir 1872, Thambus Bonvouloir 1871 and Neomathion Fleutiaux 1930. Fifty-eight species are newly recorded for Peru. A familial diagnosis as well as notes on eucnemid habitat, collecting methods, and biology are provided. This contribution is part of the 'Beetles of Peru' project.

Se presenta una lista anotada de los escarabajos eucnemídeos del Perú, basada en registros bibliográficos y examen de especímenes en colecciones de dos museos. La fauna peruana consiste aproximadamente de 107 especies en 30 géneros de ocho tribus y tres subfamilias. Se registran nueve géneros para Perú; entre ellos se encuentran: Xylophilus Mannerheim 1823, Temnillus Bonvouloir 1871, Gastraulacus Guérin-Méneville 1843, Somahenecus Cobos 1964, Silveriola Cobos 1956, Onichodon Newman 1838, Cladus Bonvouloir 1872, Thambus Bonvouloir 1871 y Neomathion Fleutiaux 1930. Recientemente se registraron cincuenta y ocho especies para Perú. Se proporciona una diagnosis de la familia, así como también notas sobre hábitat, métodos de recolección y biología de Eucnemidae. Esta publicación es una contribución del proyecto 'Escarabajos del Perú'.

Legumain-responsive functional gold nanoparticles for drug targeting delivery and treatment of subcutaneous xenograft tumor / 药学学报

Legumain, a kind of asparaginyl endopeptidase, is overexpressed in highly metastatic and highly aggressive tumor, which can undergo an enzymatic hydrolysis of substrates. We proposed a legumain-responsive functional gold nanoparticle (GNP) drug delivery system (GNPs-A&C), which was consist of Ala-Ala-Asn-Cys-Lys (AK) modified GNPs (GNPs-AK) and 2-cyano-6-aminobenzothiazole (CABT) modified GNPs (GNPs-CABT). In the circulation system, the GNPs-A&C could passively target to the tumor site through the enhanced permeability and retention (EPR) effect. Then the overexpressed legumain specifically cleave the peptide to exposure the 1,2-thiolamino group, which could take place click reaction with the cyano group of CABT, leading to the aggregation of two GNPs, these aggregates of GNPs with increased size were more likely to retain within tumor site. In vivo fluorescent imaging demonstrated GNPs-A&C could acquire an enhanced accumulation in legumain-overexpressed C6 tumor. Importantly, after tethering DOX, the GNPs-DOX-A&C showed an excellent anti-tumor effect with reduced cardiotoxicity.

The Auditory Brainstem Response in Normal Adult Mice of Different Strains / 听力学及言语疾病杂志

Objective To study the auditory brainstem response (ABR) of normal adult CBA,C57BL,Kunming and 129 mice and analyze the ABR thresholds and latencies in order to obtain normal values and standardized testing process,thereby providing important reference for future auditory hearing research in mouse.Methods Six -week-old normal mice of CBA,C57BL,Kunming and 129(each strain containing 20 ears of 20 mice) were used in this study.ABR test with both the click and tone burst were carried on.The incidence of each wave and the thresholds and latencies of various strains of mice were recorded.Results For these four strains of mice,wave Ⅱ had the highest occurrence rate and was used to determine the thresholds.Four strains of mice all were sensitive to the sound at 8,12,16 kHz,most to 12 kHz.Under anesthesia condition,the latency of each ABR wave prolonged as testing time increase,especially the waves Ⅲ ～ V which reflected the functions of the part near the cerebral center.Conclusion Under anesthesia state,for these four strains of mice,wave Ⅱ has the highest occurrence rate and is used to determine the threshold.We determine the intensity level at which Wave Ⅱ just appeared as the ABR threshold.The stain of CBA mice is the best one to establish an animal model related to hearing function research because ABR of the other three strains are not stable as the CBA mice.Wave SP can reflect the hair cell functions indirectly.

Click-Functionalized Fluorescent Nanoprobes with Folate Receptor-Targeting Ability for Cancer Cell Imaging / 分析化学

Folate receptor ( FR )-targeted fluorescent nanoprobes ( RSiNPs-Folate ) were constructed by modifying Rubpy-doped silica nanoparticles ( RSiNPs) with folic acid ( FA) based on click chemistry coupling method, which was successfully used for cancer cell imaging. Firstly, RSiNPs were prepared by St?ber method and modified with azide groups through the hydrolysis of silane coupling agents ( Az-PTES ) , then propargyl folate were conjugated onto the nanoparticle surfaces via click reaction. It was demonstrated that the FA-functionalized nanoprobes were successfully prepared by monitoring the characteristic peak of the azide group at 2105 cm-1 before and after coupling. In the condition of physiological pH, the nanoprobes exhibited strong red emission at 601 nm when excited at the 458 nm excitation wavelength. The cell imaging results showed that RSiNPs-Folate could effectively target FR-positive HeLa cells, while no obvious fluorescence was observed for FR-negative A549 cells. The receptor-mediated imaging mechanism was confirmed by free FA competition experiments. More importantly, HeLa cells could be selectively recognized and imaged in the mixing cell system. Compared with the carbodiimide conjugation protocols, the click-functionalized nanoprobes had many advantages such as simple synthesis procedures, mild reaction conditions and high yields, which could be potentially used for fluorescent labeling and imaging of different cancer cells.

Síntese e funcionalização de compostos organoenxofre: sulfóxidos, sulfetos e N-sulfinil iminas / Synthesis and functionalization of organosulfur compounds: sulfoxides, sulfides and N-sulfinyl imines

Neste trabalho promovemos a síntese de sulfóxidos vinílicos ?-substituídos através da reação de acoplamento cruzado de Suzuki-Miyaura. Também foi feita a síntese de sulfóxidos enínicos inéditos, pela adição do nucleófilo no carbono ß-sulfóxido. Esses compostos eram passíveis de serem submetidos a reação de rearranjo de Pummerer aditivo e assim gerarem uma pequena biblioteca de compostos α-tioaldeídos. Um desses aldeídos sintetizados foi empregado na reação de formação de uma imina propargílica, com consequente reação de CuAAC formando iminas triazólicas. Outras iminas arílicas foram sintetizadas, passando por uma etapa de redução, com intuito de se obter a amina livre, para que fosse feita a reação de ciclização com auxílio de um agente eletrofílico. Outra classe de composto organoenxofre foi sintetizada, as N-sulfinil imina, que após a reação de acoplamento cruzado de Sonogashira, com consequente remoção de um grupo protetor e a formação do anel heterocíclico, foram obtidos compostos triazólicos N-sulfinil imínicos.

In this work we promote the synthesis of α-substituted vinylic sulfoxides through the Suzuki-Miyaura cross coupling reaction. Also the synthesis of unpublished enynic sulfoxides was made, by the addition of the nucleophile in the ß-sulfoxide carbon. These compounds were susceptible to additive Pummerer rearragement reaction and thus generated a small library of compounds. One of these aldehydes synthesized was used in the formation reaction of a propargyl imine, with consequent CuAAC reaction, forming triazol imines. Other aryl imines were synthesized, undergoing a reduction step, in order to obtain the free amine, so that the cyclization reaction was carried out with the aid of an electrophilic agent. Another class of organosulfur compound was synthesized, the N-sulfinyl imine, which after the Sonogashira cross-coupling reaction, with consequent removal of a protecting group and formation of the heterocyclic ring, N-sulfinyl imine triazolic compounds were obtained.