Constructing metal-organic framework-derived Mn2O3multishelled hollow nanospheres for high-performance cathode of aqueous zinc-ion batteries.

Herein, we successfully synthesize Mn2O3multishelled hollow nanospheres through simply oxidizing Mn-based metal-organic framework microspheres. The number of the shells reaches 4. Many cavities and nanograins are hidden underneath the shell. The multishelled hollow structure brings about a wide hierarchical mesopore size range, large pore volume (0.26 cm3g-1) and high specific surface area (117.6 m2g-1). The superior zinc-ion storage performance may be achieved. The reversible capacity reaches 453 mAh g-1at current density of 0.1 A g-1. After 500 cycles at 1 A g-1, the discharge capacity of 152.8 mAh g-1is still delivered. The discharge capacity at 1.5 A g-1stabilizes at 107 mAh g-1. The zinc storage process is further studied through kinetics analyses. It is found that in the zinc storage process, ion diffusion process and capacitive process occur simultaneously, and the capacitive process is dominant. The excellent electrochemical performance is mainly attributed to the multishelled hollow nanosphere structure of Mn2O3. This structure promotes contact of electrode materials/electrolyte, offers more active sites, facilitates infiltration of electrolyte, buffer volume change of Mn2O3, improving electrochemical activity, reaction kinetics and cycling performance of Mn2O3. Overall, Mn2O3multishelled hollow nanosphere is an excellent cathode material for aqueous zinc-ion batteries.

Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of ß-catenin.

It is a widely held belief that the sole effect of muscle on bone is through mechanical loading. However, as the two tissues are intimately associated, we hypothesized that muscle myokines may have positive effects on bone. We found that factors produced by muscle will protect osteocytes from undergoing cell death induced by dexamethasone (dex), a glucocorticoid known to induce osteocyte apoptosis thereby compromising their capacity to regulate bone remodeling. Both the trypan blue exclusion assay for cell death and nuclear fragmentation assay for apoptosis were used. MLO-Y4 osteocytes, primary osteocytes, and MC3T3 osteoblastic cells were protected against dex-induced apoptosis by C2C12 myotube conditioned media (MT-CM) or by CM from ex vivo electrically stimulated, intact extensor digitorum longus (EDL) or soleus muscle derived from 4 month-old mice. C2C12 MT-CM, but not undifferentiated myoblast CM prevented dex-induced cell apoptosis and was potent down to 0.1 % CM. The CM from EDL muscle electrically stimulated tetanically at 80 Hz was more potent (10 fold) in prevention of dex-induced osteocyte death than CM from soleus muscle stimulated at the same frequency or CM from EDL stimulated at 1 Hz. This suggests that electrical stimulation increases production of factors that preserve osteocyte viability and that type II fibers are greater producers than type I fibers. The muscle factor(s) appears to protect osteocytes from cell death through activation of the Wnt/ß-catenin pathway, as MT-CM induces ß-catenin nuclear translocation and ß-catenin siRNA abrogated the positive effects of MT-CM on dex-induced apoptosis. We conclude that muscle cells naturally secrete factor(s) that preserve osteocyte viability.

Hierarchical hollow superstructure cobalt selenide bird nests for high-performance lithium storage.

The inferior cycling performance caused by large volume variation is the main problem that restricts the application of cobalt selenides in lithium-ion batteries. Herein, we synthesize raspberry-like Co-ethylene glycol precursor. It is further selenized into the hierarchical hollow superstructure CoSe2/CoSe bird nests that are assembled by the hollow nanosphere units of CoSe2 and CoSe nanocrystalline. CoSe2/CoSe bird nests achieve excellent cycling performance, high reversible capacity and satisfactory rate capability (1361 mAh/g at 1 A/g after 1000 cycles, 579 mAh/g at 2 A/g after 2000 cycles, 315 mAh/g at 5 A/g after 1000 cycles). Electrochemical kinetics analyses and ex-situ material characterization reveal that the surface capacitive behavior controls the electrochemical reaction, and the composite has low reaction impedance, fast and stable Li+ diffusion, and superior structural stability. The superior lithium storage performance is attributed to the unique superstructure bird nest. Large specific surface area, abundant hierarchical pores and the opening mouth result in high electrochemical activity, which induces high reversible capacity. The small hollow nanosphere units, the sufficiently thick hierarchical porous superstructure shell and the large hollow interior bring about the strong synergistic effect to improve cycling performance. The intimately coupling of CoSe2/CoSe nanocrystalline and the hollow nanosphere units guarantees high conductivity. This work has greatly enriched the understanding of structure design of high-performance cobalt selenide anodes.

Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors: heterocyclic ring systems containing P1' and P2' substituents.

As an extension of our earlier work based upon a single penicillin-derived thiazolidine moiety we have found that the decahydroisoquinoline grouping, also present in Ro 31-8959, is an effective replacement for one of the thiazolidine units in C2 symmetric penicillin-derived dimers. Reaction of racemic epoxide 6 with [3S-[3 alpha, 4a alpha, 8a alpha]]-decahydro-N-(1,1-dimethylethyl)-3- isoquinolinecarboxamide gave diasteroisomers 34a and 34b. The stereochemistry of the hydroxyl grouping of 34a was determined to be (S). Reaction of the amines derived from 34a and 34b with thiazolidine 8a gave 50 and 51, respectively. Compound 50 was a potent inhibitor of HIV proteinase (IC50 = 23 nM) with antiviral activity against HIV-1 in vitro (EC50 C8166 cells = 50 nM). However, a poor pharmacokinetic profile in the dog for compound 50 and its analogues, in keeping with earlier studies on penicillin-derived dimers in three species, precluded their development as potential antivirals.

Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors containing a stereochemically unique peptide isostere.

A series of HIV-1 proteinase inhibitors was synthesized based upon a single penicillin derived thiazolidine moiety. Reaction of the C-4 carboxyl group with (R)-phenylalaninol gave amide 10 which was a moderately potent inhibitor of HIV-1 proteinase (IC50 = 0.15 microM). Further modifications based on molecular modeling studies led to compound 48 which contained a stereochemically unique statine-based isostere. This was a potent competitive inhibitor (Ki = 0.25 nM) with antiviral activity against HIV-1 in vitro (5 microM). Neither modification to the benzyl group in an attempt to improve interaction with the S2' pocket, nor introduction of a hydrogen bond donating group to interact with residue Gly48' resulted in improved inhibitory or antiviral activity.

Epidemiology of bluetongue viruses in the American tropics. Regional Bluetongue Team.

A study of the epidemiology of bluetongue viruses is in progress with the collaboration of 11 Central American and Caribbean countries. To date, over 200 bluetongue virus isolates have been obtained from cattle and sheep in sentinel groups distributed in the participating countries. Bluetongue serotypes identified include 1, 3, 6, and 12, virus types not previously recorded in the Western Hemisphere. Although the clinical impact of bluetongue virus infections in this hyperendemic environment appears to be minimal, the ubiquity of infection causes restrictions on the export of ruminant livestock and germ plasm. The stability of the Caribbean region ecosystem and the long-range implications of the interface with the northern temperate bluetongue virus ecosystem are reviewed.

Infection of duck plague carriers with Pasteurella multocida and P. anatipestifer.

Mallards (Anas platyrhynchos platyrhynchos) and white pekin ducks (Anas platyrhynchos domesticus) were infected with duck plague virus and challenged with LD20's of Pasteurella multocida and P. anatipestifer. There was no difference between mortality rates of duck plague-infected ducks and controls, suggesting that these organisms do not act synergistically under the conditions of our experiments. There was a difference of about 500-fold between the LD20 of P. multocida for mallards and that for white pekin ducks, indicating that mallards are much more susceptible to avian cholera than white pekin ducks.

Epidemiologic study of bluetongue viruses in Central America and the Caribbean: 1986-1988. Regional Bluetongue Team.

Results of a prospective serologic and virologic study of ruminant livestock in Central America and the Caribbean islands revealed bluetongue virus (BTV) to be enzootic in the 9 countries participating in the study. Bluetongue virus serotypes 1, 3, 6, and 12 were isolated from sentinel animals. To the authors' knowledge, these are the first isolations of BTV from the region studied and the first isolations of these serotypes in the Western Hemisphere. Clinical disease attributable to BTV infection was not observed in sentinel animals. The incidence pattern, with respect to age and geographic location, was determined. The need to evaluate the epizootiologic features or arthropod-borne viruses (arboviruses) on a regional ecologic basis is stressed.

Bluetongue virus isolations from vectors and ruminants in Central America and the Caribbean. Interamerican Bluetongue Team.

A regional prospective study of the epidemiology of bluetongue virus (BTV) serotypes covering 11 countries in Central America and the Caribbean took place between 1987 and 1992. Active surveillance revealed BTV infection to be endemic in the absence of confirmed indigenous cases of bluetongue. During the 6-year span of the study, over 300 BTV isolations were obtained from cattle and sheep. Results of the earlier years of the study were summarized, and surveillance activities in the concluding months of the study from November 1990 to February 1992 were evaluated. Forty-five BTV isolations were made during this time, 44 from sentinel cattle and 1 from a ram with clinical signs compatible with contagious ecthyma. Virus isolation from potential vectors also was attempted, yielding a further 9 BTV isolates from parous Culicoides insignis and C pusillus, 2 BTV isolates from blood-engorged C filarifer, and 1 epizootic hemorrhagic disease virus type-2 isolate from parous C pusillus. Our extensive network of sentinel herds in the region detected BTV-1 as the predominant serotype in Central America in 1991, after an apparent absence of 1 year in the sentinel animals. Other serotypes in Central America at that time included BTV-3 and BTV-6. In Puerto Rico and the Dominican Republic, BTV-4 became the predominant serotype, without detection of BTV-8 and BTV-17, which were common in recent years of the study. The serotypes found in the Caribbean Basin continued to have marked differences from those in North America. The importance of viewing bluetongue as an infection, the distribution of which is determined principally by ecologic factors, is emphasized.

DNA chain termination activity and inhibition of human immunodeficiency virus reverse transcriptase by carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine triphosphate.

Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, NSC 614846) is an anti-retroviral agent that may be useful in the treatment of AIDS. We have examined the ability of (-)-enantiomeric carbovir triphosphate to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49). A comparison of inhibition kinetics was made with 3'-azido-2',3'-dideoxythymidine triphosphate and phosphonoformate. Inhibition of the reverse transcriptase was evaluated using poly(rA).oligo(dT)12-18, poly(rC).oligo(dG)12-18, or influenza virion RNA template with a specific oligodeoxynucleotide as primer. (-)-Carbovir 5'-triphosphate was shown to be a potent inhibitor of HIV-1 reverse transcriptase with an apparent Ki similar to that of 3'-azido-2',3'-dideoxythymidine triphosphate. Chain elongation studies utilizing an MS2 RNA template showed that (-)-carbovir 5'-triphosphate terminated transcription at positions identical to those where dideoxy-GTP terminated. This indicates that (-)-carbovir 5'-monophosphate is incorporated into the newly synthesized DNA and terminates transcription at that point. We conclude that (-)-carbovir 5'-triphosphate is a potent inhibitor of the HIV-1 reverse transcriptase enzyme and that (-)-carbovir most likely inhibits HIV by activity at the triphosphate level by a combination of direct competition for binding of the natural deoxynucleoside triphosphates to the reverse transcriptase and chain termination.

Epidemiology of bluetongue in Central America and the Caribbean: initial entomological findings. Regional Bluetongue Team.

Forty-four species of Culicoides (Diptera: Ceratopogonidae) were caught in insect light traps during the first 2 years of studies on the epidemiology of bluetongue virus in the Caribbean and Central America. Traps were operated near sentinel ruminants which were bled monthly for serologic evaluation and then virus isolation. More than 570,000 individuals were identified. Culicoides insignis Lutz accounted for 90% of the catch, C. filarifer Hoffman/C. ocumarensis Ortiz 5%, C. furens Poey 3% and C. pusillus Lutz 2%. Other species accounted for less than 1% of the total catch. Sentinel ruminants became seropositive when C. insignis populations were high at many study sites. At a few sites C. pusillus and C. filarifer/C. ocumarensis were predominant or were present in large numbers during seroconversions of sentinels. Virus isolations were obtained from sentinel ruminants during times when these same species were present in large populations.

The synthesis and antiviral activity of 4-fluoro-1-beta-D-ribofuranosyl-1H-pyrazole-3-carboxamide.

A novel fluoropyrazole ribonucleoside has been shown to have significant anti-influenza activity in vitro. The compound is compared and contrasted with the structurally-related compound ribavirin in attempts to identify factors having significant bearing on the mode of action of both compounds.