Targeting Ser78 phosphorylation of Hsp27 achieves potent antiviral effects against enterovirus A71 infection.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

On-chip droplet analysis and cell spheroid screening by capillary wrapping enabled shape-adaptive ferrofluid transporters.

Non-invasive droplet manipulation with no physical damage to the sample is important for the practical value of manipulation tools in multidisciplinary applications from biochemical analysis and diagnostics to cell engineering. It is a challenge to achieve this for most existing photothermal, electric stimuli, and magnetic field-based technologies. Herein, we present a droplet handling toolbox, the ferrofluid transporter, for non-invasive droplet manipulation in an oil environment. It involves the transport of droplets with high robustness and efficiency owing to low interfacial friction. This capability caters to various scenarios including droplets with varying components and solid cargo. Moreover, we fabricated a droplet array by transporter positioning and achieved droplet gating and sorting for complex manipulation in the droplet array. Benefiting from the ease of scale-up and high biocompatibility, the transporter-based droplet array can serve as a digital microfluidic platform for on-chip droplet-based bioanalysis, cell spheroid culture, and downstream drug screening tests.

High-Performance Supramolecular Organogel Adhesives for Antimicrobial Applications in Diverse Conditions.

Supramolecular organogel coatings that can disinfect the deposited microbial pathogens are emerging as an effective vehicle to prevent pathogen transmission. However, the development of anti-pathogen supramolecular adhesives with mechanical robustness and controlled oil inclusion is technically challenging. Here, we report supramolecular adhesives with mechanical integrity and robust interfacial adhesion over a wide range of biogenic antimicrobial oil. Bifunctional monomers are synthesized and assembled into linear polymers with semicrystalline stackings through hierarchical hydrogen bonds, where incorporated bioactive oil could regulate the semicrystalline stackings into nanosized crystalline domains through intermolecular hydrogen bonds. The abundant bonding motifs provided by the supramolecular cross-linked networks could accommodate oil molecules with high inclusion capability and provide more interfacial binding sites with high adhesion strength, and the nanosized crystalline domains could stabilize the organogel network and compensate for the interactions with oil molecules to enhance structural and mechanical stability. In addition, rapid healing, robust adhesion, and antimicrobial and antiviral properties of the resultant organogel coatings are demonstrated. This study paves the way for the development of high-performance antimicrobial supramolecular adhesives with controlled oil inclusion, showing potential applications in soft robotics, tissue engineering, and biomedical devices.

Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes.

Despite the enormous developments in asymmetric catalysis, the basis for asymmetric induction is largely limited to the spatial interaction between the substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between two aryl groups without a directing group or electronic manipulation. Here we address this challenge by using a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With versatile 2-indole imine methide as the platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

Comparing different patterns for managing febrile children in the ED between emergency and pediatric physicians: impact on patient outcome.

OBJECTIVE: The management of children with fever of indefinite source still remains controversial. This study aimed to compare different practice patterns between pediatric physicians (PPs) and emergency physicians (EPs) in the management of pediatric fever in the emergency department (ED) and correlate them to existing practice guidelines. Their impact on patient outcomes was also discussed. METHODS: Medical records of patients 3 to 36 months of age who presented to the ED with fever of indefinite source from June 1 to December 31, 2006, were retrospectively reviewed on day 5 after the patient's first visit. At the same time, telephone follow-up was carried out to determine whether the patient had been visiting or being admitted to another clinic or hospital after discharge. Variation in practice patterns were compared for the number of laboratory tests, ED length of stay (LOS), and the rate of immediate admission. Patient outcomes were measured as the rate of unscheduled revisit within 72 hours and the rate of subsequent admission. Compliance with existing practice guidelines between PPs and EPs were evaluated by dividing all eligible patients into 3 groups: (1) toxic appearing patients (group A), (2) nontoxic patients with body temperature (BT) > or = 39 degrees C (group B), and (3) nontoxic patients with BT below 39 degrees C (group C). RESULTS: A total of 345 patients who met the inclusion and exclusion criteria were enrolled into this study. Pediatric physicians and EPs treated 163 and 182 febrile children, respectively. In group A, PPs admitted more patients than EPs (41% vs 12 %), whereas more unscheduled revisits were seen in EP-treated patients (44% vs 10%). In group B, PPs ordered more laboratory tests than EPs (2.3 vs 0.7 tests per patient), and their patients also had a longer ED LOS (3.4 +/- 3.2 vs 1.5 +/- 1.1 hours). However, no difference was found in their rates of immediate admission and unscheduled revisit. In group C, PPs admitted more patients (15% vs 0%) and ordered more laboratory tests (2.0 vs 0.5 tests/patient) than EPs. Longer ED LOS (3.3 +/- 3.9 vs 1.0 +/- 1.4 hours) was also noted among PP-treated patients. However, no difference was noted in their rates of unscheduled revisit. In all groups, the rates of subsequent admission were similar. CONCLUSION: Compliance with existing practice guidelines (admit the toxic cases and work up those with BT > or = 39 degrees C) was higher among PPs, which resulted in a lower rate of unscheduled revisit, but no significant difference was found in the rate of subsequent admission.