10 research outputs found
Engineering Antimicrobial Peptides with Improved Antimicrobial and Hemolytic Activities
The
rapid rise of antibiotic resistance in pathogens becomes a
serious and growing threat to medicine and public health. Naturally
occurring antimicrobial peptides (AMPs) are an important line of defense
in the immune system against invading bacteria and microbial infection.
In this work, we present a combined computational and experimental
study of the biological activity and membrane interaction of the computationally
designed Bac2A-based peptide library. We used the MARTINI coarse-grained
molecular dynamics with adaptive biasing force method and the umbrella
sampling technique to investigate the translocation of a total of
91 peptides with different amino acid substitutions through a mixed
anionic POPE/POPG (3:1) bilayer and a neutral POPC bilayer, which
mimic the bacterial inner membrane and the human red blood cell (hRBC)
membrane, respectively. Potential of mean force (PMF, free energy
profile) was obtained to measure the free energy barrier required
to transfer the peptides from the bulk water phase to the water–membrane
interface and to the bilayer interior. Different PMF profiles can
indeed identify different membrane insertion scenarios by mapping
out peptide–lipid energy landscapes, which are correlated with
antimicrobial activity and hemolytic activity. Computationally designed
peptides were further tested experimentally for their antimicrobial
and hemolytic activities using bacteria growth inhibition assay and
hemolysis assay. Comparison of PMF data with cell assay results reveals
a good correlation of the peptides between predictive transmembrane
activity and antimicrobial/hemolytic activity. Moreover, the most
active mutants with the balanced substitutions of positively charged
Arg and hydrophobic Trp residues at specific positions were discovered
to achieve the improved antimicrobial activity while minimizing red
blood cell lysis. Such substitutions provide more effective and cooperative
interactions to distinguish the peptide interaction with different
lipid bilayers. This work provides a useful computational tool to
better understand the mechanism and energetics of membrane insertion
of AMPs and to rationally design more effective AMPs
DataSheet1_Carbon dots with light-responsive oxidase-like activity for colorimetric detection of dopamine and the catalytic mechanism.DOCX
Introduction: Dopamine is one of the most significant neurotransmitters and plays an important role in the management of cognitive functions such as learning, memory, and behavior. The disorder of dopamine is associated with many major mental diseases. It is necessary to develop selective methods for the detection of dopamine.Methods: In this work, carbon dots (CDs) were synthesized by a solvothermal route using glutathione, L-histidine, and formamide as sources.Results: Under light irradiation, The CDs convert dissolved oxygen to singlet oxygen (1O2), which could oxidize TMB. When reduced dopamine was present, it suppressed the catalysis of CDs, then the absorption of the CDs-coupled TMB complex at 652 nm was diminished. Furthermore, it was revealed that the surface groups including hydroxyl, amino, carbonyl, and carboxyl groups of CDs were related to their light-responsive catalytic activity by surface modification. In the range of 0.5-15 μM, the CDs could afford a LOD of 0.25 μM for dopamine detection with fine linearity, also showing good selectivity.Discussion: The results from fetal bovine serum indicated the good applicability of the CDs in the determination of dopamine.</p
Probing the Structural Dependence of Carbon Space Lengths of Poly(<i>N</i>‑hydroxyalkyl acrylamide)-Based Brushes on Antifouling Performance
Numerous
biocompatible antifouling polymers have been developed
for a wide variety of fundamental and practical applications in drug
delivery, biosensors, marine coatings, and many other areas. Several
antifouling mechanisms have been proposed, but the exact relationship
among molecular structure, surface hydration property, and antifouling
performance of antifouling polymers still remains elusive. Here this
work strives to provide a better understanding of the structure–property
relationship of poly(<i>N</i>-hydroxyalkyl acrylamide)-based
materials. We have designed, synthesized, and characterized a series
of polyHAAA brushes of various carbon spacer lengths (CSLs), that
is, poly(<i>N</i>-hydroxymethyl acrylamide) (polyHMAA),
poly(<i>N</i>-(2-hydroxyethyl)acrylamide) (polyHEAA), poly(<i>N</i>-(3-hydroxypropyl)acrylamide) (polyHPAA), and poly(<i>N</i>-(5-hydroxypentyl)acrylamide) (polyHPenAA), to study the
structural dependence of CSLs on their antifouling performance. HMAA,
HEAA, HPAA, and HPenAA monomers contained one, two, three, and five
methylene groups between hydroxyl and amide groups, while the other
groups in polymer backbones were the same as each other. The relation
of such small structural differences of polymer brushes to their surface
hydration and antifouling performance was studied by combined experimental
and computational methods including surface plasmon resonance sensors,
sum frequency generation (SFG) vibrational spectroscopy, cell adhesion
assay, and molecular simulations. Antifouling results showed that
all polyHAAA-based brushes were highly surface resistant to protein
adsorption from single protein solutions, undiluted blood serum and
plasma, as well as cell adhesion up to 7 days. In particular, polyHMAA
and polyHEAA with the shorter CSLs exhibited higher surface hydration
and better antifouling ability than polyHPMA and polyHPenAA. SFG and
molecular simulations further revealed that the variation of CSLs
changed the ratio of hydrophobicity/hydrophilicity of polymers, resulting
in different hydration characteristics. Among them, polyHMAA and polyHEAA
with the shorter CSLs showed the highest potency for surface hydration
and antifouling abilities, while polyHPenAA showed the lowest potency.
The combination of both hydroxyl and amide groups in the same polymer
chain provides a promising structural motif for the design of new
effective antifouling materials
Supplementary Data: Phylogenetic Analysis Result, EDS Elemental Map, and Limb Proportions of Gansubatrachus qilianensis from A cretaceous frog with eggs from northwestern China provides fossil evidence for sexual maturity preceding skeletal maturity in anurans
Mesozoic fossils of frogs are rare in the palaeontological record, particularly those exhibiting soft tissues that offer limited insights into early life-history characteristics. Here we report on a skeletally immature frog from the Lower Cretaceous of northwest China, with egg masses in the body and eggs in the oviduct, indicative of a gravid female. CT reconstruction of the specimen allows referral to Gansubatrachus qilianensis and we assign it as a paratype complementing the diagnosis of the type species. The new fossil, which might represent a younger individual than the holotype of Gansubatrachus, shows that sexual maturation occurred before full adulthood in this frog and provides evidence of death linked to mating behaviour. We also discuss other potential sources of variation and life-history traits of Gansubatrachus. The new finding represents the oldest Early Cretaceous frog preserving in situ eggs and provides a glimpse into ancient anuran development during Mesozoic times
Comparative Study of Graphene Hydrogels and Aerogels Reveals the Important Role of Buried Water in Pollutant Adsorption
Water
as the universal solvent has well-demonstrated its ability
to dissolve many substances, but buried water inside different nanoporous
materials always exhibits some unusual behaviors. Herein, 3D porous
graphene hydrogel (GH) is developed as a super-adsorbent to remove
different pollutants (antibiotics, dyes, and heavy ions) for water
purification. Due to its highly porous structure and high content
of water, GH also demonstrated its super adsorption capacity for adsorbing
and removing different pollutants (antibiotics, dyes, and heavy ions)
as compared to conventional graphene aerogel (GA). More fundamentally,
the buried-water enhanced adsorption mechanism was proposed and demonstrated,
such that buried water in GH plays the combinatorial roles as (1)
supporting media, (2) transport nanochannels, and (3) hydrogen bondings
in promoting pollutant adsorption. In parallel, molecular dynamics
simulations further confirm that buried water in GH has the stronger
interaction with pollutants via hydrogen bonds than other buried alcohols.
GH integrates the merit of both graphene (e.g., fine chemical resistance
and excellent mechanical property) and hydrogel (e.g., high water
content, porous structure, and simple solution-based processability
and scalability), giving it promising potential for environmental
applications
First fossil evidence for a new frog from the Early Cretaceous of the Jiuquan Basin, Gansu Province, north-western China
Based on a well-preserved incomplete skeleton, a new frog, Gansubatrachus qilianensis gen. et sp. nov., is described from the Lower Cretaceous Zhonggou Formation of Jiuquan Basin, Gansu Province, north-western China. This species differs from other frogs in a unique combination of characteristics, such as a robust and non-bifurcated alary process on the premaxilla, a ‘V’-shaped parahyoid, a paired sphenethmoid, eight presacral vertebrae, three pairs of free ribs, and unexpanded sacral diapophyses. Phylogenetic analysis based on parsimony suggests that Gansubatrachus is a basal Lalagobatrachia. This discovery of a new frog fossil from the Early Cretaceous of north-west China expands the diversity of fossil frogs in East Asia and provides new material for further studies on the distribution and evolutionary history of Cretaceous Asian anurans. http://zoobank.org/urn:lsid:zoobank.org:pub:A80B417A-F9C6-4704-B473-FBBA6CDC8C2B</p
Dual Salt- and Thermoresponsive Programmable Bilayer Hydrogel Actuators with Pseudo-Interpenetrating Double-Network Structures
Development of smart
soft actuators is highly important for fundamental research and industrial
applications but has proved to be extremely challenging. In this work,
we present a facile, one-pot, one-step method to prepare dual-responsive
bilayer hydrogels, consisting of a thermoresponsive poly(<i>N</i>-isopropylacrylamide) (polyNIPAM) layer and a salt-responsive poly(3-(1-(4-vinylbenzyl)-1<i>H</i>-imidazol-3-ium-3-yl)propane-1-sulfonate) (polyVBIPS) layer.
Both polyNIPAM and polyVBIPS layers exhibit a completely opposite
swelling/shrinking behavior, where polyNIPAM shrinks (swells) but
polyVBIPS swells (shrinks) in salt solution (water) or at high (low)
temperatures. By tuning NIPAM:VBIPS ratios, the resulting polyNIPAM/polyVBIPS
bilayer hydrogels enable us to achieve fast and large-amplitude bidirectional
bending in response to temperatures, salt concentrations, and salt
types. Such bidirectional bending, bending orientation, and degree
can be reversibly, repeatedly, and precisely controlled by salt- or
temperature-induced cooperative swelling–shrinking properties
from both layers. Based on their fast, reversible, and bidirectional
bending behavior, we further design two conceptual hybrid hydrogel
actuators, serving as a six-arm gripper to capture, transport, and
release an object and an electrical circuit switch to turn on-and-off
a lamp. Different from the conventional two- or multistep methods
for preparation of bilayer hydrogels, our simple, one-pot, one-step
method and a new bilayer hydrogel system provide an innovative concept
to explore new hydrogel-based actuators through combining different
responsive materials that allow us to program different stimuli for
soft and intelligent materials applications
De Novo Design of Self-Assembled Hexapeptides as β‑Amyloid (Aβ) Peptide Inhibitors
The
ability of peptides to construct specific secondary structures
provides a useful function for biomaterial design that cannot be achieved
with traditional organic molecules and polymers. Inhibition of amyloid
formation is a promising therapeutic approach for the treatment of
neurodegenerative diseases. Existing peptide-based inhibitors are
mainly derived from original amyloid sequences, which have very limited
sequence diversity and activity. It is highly desirable to explore
other peptide-based inhibitors that are not directly derived from
amyloid sequences. Here, we develop a hybrid high-throughput computational
method to efficiently screen and design hexapeptide inhibitors against
amyloid-β (Aβ) aggregation and toxicity from the first
principle. Computationally screened/designed inhibitors are then validated
for their inhibition activity using biophysical experiments. We propose
and demonstrate a proof-of-concept of the “like-interacts-like”
design principle that the self-assembling peptides are able to interact
strongly with conformationally similar motifs of Aβ peptides
and to competitively reduce Aβ–Aβ interactions,
thus preventing Aβ aggregation and Aβ-induced toxicity.
Such a de novo design can also be generally applicable to design new
peptide inhibitors against other amyloid diseases, beyond traditional
peptide inhibitors with homologous sequences to parent amyloid peptides
Dual Salt- and Thermoresponsive Programmable Bilayer Hydrogel Actuators with Pseudo-Interpenetrating Double-Network Structures
Development of smart
soft actuators is highly important for fundamental research and industrial
applications but has proved to be extremely challenging. In this work,
we present a facile, one-pot, one-step method to prepare dual-responsive
bilayer hydrogels, consisting of a thermoresponsive poly(<i>N</i>-isopropylacrylamide) (polyNIPAM) layer and a salt-responsive poly(3-(1-(4-vinylbenzyl)-1<i>H</i>-imidazol-3-ium-3-yl)propane-1-sulfonate) (polyVBIPS) layer.
Both polyNIPAM and polyVBIPS layers exhibit a completely opposite
swelling/shrinking behavior, where polyNIPAM shrinks (swells) but
polyVBIPS swells (shrinks) in salt solution (water) or at high (low)
temperatures. By tuning NIPAM:VBIPS ratios, the resulting polyNIPAM/polyVBIPS
bilayer hydrogels enable us to achieve fast and large-amplitude bidirectional
bending in response to temperatures, salt concentrations, and salt
types. Such bidirectional bending, bending orientation, and degree
can be reversibly, repeatedly, and precisely controlled by salt- or
temperature-induced cooperative swelling–shrinking properties
from both layers. Based on their fast, reversible, and bidirectional
bending behavior, we further design two conceptual hybrid hydrogel
actuators, serving as a six-arm gripper to capture, transport, and
release an object and an electrical circuit switch to turn on-and-off
a lamp. Different from the conventional two- or multistep methods
for preparation of bilayer hydrogels, our simple, one-pot, one-step
method and a new bilayer hydrogel system provide an innovative concept
to explore new hydrogel-based actuators through combining different
responsive materials that allow us to program different stimuli for
soft and intelligent materials applications
Two-Step Chemoenzymatic Detection of <i>N</i>‑Acetylneuraminic Acid−α(2-3)-Galactose Glycans
Sialic
acids are typically linked α(2-3) or α(2-6)
to the galactose that located at the non-reducing terminal end of
glycans, playing important but distinct roles in a variety of biological
and pathological processes. However, details about their respective
roles are still largely unknown due to the lack of an effective analytical
technique. Herein, a two-step chemoenzymatic approach for the rapid
and sensitive detection of <i>N</i>-acetylneuraminic
acid−α(2-3)-galactose glycans is described