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1.
Proc Natl Acad Sci U S A ; 120(33): e2305403120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549270

RESUMO

Continually emerging SARS-CoV-2 variants of concern that can evade immune defenses are driving recurrent epidemic waves of COVID-19 globally. However, the impact of measures to contain the virus and their effect on lineage diversity dynamics are poorly understood. Here, we jointly analyzed international travel, public health and social measures (PHSM), COVID-19 vaccine rollout, SARS-CoV-2 lineage diversity, and the case growth rate (GR) from March 2020 to September 2022 across 63 countries. We showed that despite worldwide vaccine rollout, PHSM are effective in mitigating epidemic waves and lineage diversity. An increase of 10,000 monthly travelers in a single country-to-country route between endemic countries corresponds to a 5.5% (95% CI: 2.9 to 8.2%) rise in local lineage diversity. After accounting for PHSM, natural immunity from previous infections, and waning immunity, we discovered a negative association between the GR of cases and adjusted vaccine coverage (AVC). We also observed a complex relationship between lineage diversity and vaccine rollout. Specifically, we found a significant negative association between lineage diversity and AVC at both low and high levels but not significant at the medium level. Our study deepens the understanding of population immunity and lineage dynamics for future pandemic preparedness and responsiveness.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Vacinas contra COVID-19 , Saúde Pública , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Pandemias/prevenção & controle
2.
J Am Chem Soc ; 146(11): 7533-7542, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38451015

RESUMO

Impact-stiffening materials that undergo a strain rate-induced soft-to-rigid transition hold great promise as soft armors in the protection of the human body and equipment. However, current impact-stiffening materials, such as polyborosiloxanes and shear-thickening fluids, often exhibit a limited impact-stiffening response. Herein, we propose a design strategy for fabricating highly impact-stiffening supramolecular polymer networks by leveraging high-entropy-penalty physical interactions. We synthesized a fully biobased supramolecular polymer comprising poly(α-thioctic acid) and arginine clusters, whose chain dynamics are governed by highly specific guanidinium-carboxylate salt-bridge hydrogen bonds. The resulting material exhibits an exceptional impact-stiffening response of ∼2100 times, transitioning from a soft dissipating state (21 kPa, 0.1 Hz) to a highly stiffened glassy state (45.3 MPa, 100 Hz) with increasing strain rates. Moreover, the material's high energy-dissipating and hot-melting properties bring excellent damping performance and easy hybridization with other scaffolds. This entropy-driven approach paves the way for the development of next-generation soft, sustainable, and impact-resistant materials.

3.
Small ; : e2401164, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700067

RESUMO

Moisture usually deteriorates polymers' mechanical performance owing to its plasticizing effect, causing side effects in their practical load-bearing applications. Herein, a simple binary ionogel consisting of an amphiphilic polymer network and a hydrophobic ionic liquid (IL) is developed with remarkable stiffening effect after moisture absorption, demonstrating a complete contrast to water-induced softening effect of most polymer materials. Such a moisture-induced stiffening behavior is induced by phase separation after hydration of this binary ionogel. Specifically, it is revealed that hydrogen (H)-bonding structures play a dominant role in the humidity-responsive behavior of the ionogel, where water will preferentially interact with polymer chains through H-bonding and break the polymer-IL H-bonds, thus leading to phase separation structures with modulus boosting. This work may provide a facile and effective molecular engineering route to construct mechanically adaptive polymers with water-induced dramatic stiffening for diverse applications.

4.
PLoS Comput Biol ; 19(9): e1011492, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37721947

RESUMO

China had conducted some of the most stringent public health measures to control the spread of successive SARS-CoV-2 variants. However, the effectiveness of these measures and their impacts on the associated disease burden have rarely been quantitatively assessed at the national level. To address this gap, we developed a stochastic age-stratified metapopulation model that incorporates testing, contact tracing and isolation, based on 419 million travel movements among 366 Chinese cities. The study period for this model began from September 2022. The COVID-19 disease burden was evaluated, considering 8 types of underlying health conditions in the Chinese population. We identified the marginal effects between the testing speed and reduction in the epidemic duration. The findings suggest that assuming a vaccine coverage of 89%, the Omicron-like wave could be suppressed by 3-day interval population-level testing (PLT), while it would become endemic with 4-day interval PLT, and without testing, it would result in an epidemic. PLT conducted every 3 days would not only eliminate infections but also keep hospital bed occupancy at less than 29.46% (95% CI, 22.73-38.68%) of capacity for respiratory illness and ICU bed occupancy at less than 58.94% (95% CI, 45.70-76.90%) during an outbreak. Furthermore, the underlying health conditions would lead to an extra 2.35 (95% CI, 1.89-2.92) million hospital admissions and 0.16 (95% CI, 0.13-0.2) million ICU admissions. Our study provides insights into health preparedness to balance the disease burden and sustainability for a country with a population of billions.


Assuntos
COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Saúde Pública , Epidemias/prevenção & controle , China/epidemiologia
5.
Appl Microbiol Biotechnol ; 108(1): 206, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353738

RESUMO

Plant cells serve as versatile platforms for the production of high-value recombinant proteins. This study explored the efficacy of utilizing an endogenous αAmy3 promoter for the expression of a bioactive pharmaceutical protein, specifically the mature region of human bone morphogenetic protein 2 (hBMP2m). Utilizing a refined CRISPR/Cas9-mediated intron-targeting insertion technique, which incorporates an artificial 3' splicing site upstream of the target gene, we achieved a transformation efficiency of 13.5% in rice calli that carried the rice-codon optimized mature region of hBMP2 cDNA (rhBMP2m) in the αAmy3 intron 1. Both homozygous and heterozygous rhBMP2m knock-in rice suspension cell lines were generated. These lines demonstrated the endogenous αAmy3 promoter regulated rhBMP2m mRNA and rhBMP2m recombinant protein expression, with strongly upregulation in respond to sugar depletion. The homozygous rhBMP2m knock-in cell line yielded an impressive 21.5 µg/mL of rhBMP2m recombinant protein, accounting for 1.03% of the total soluble protein. The high-yield expression was stably maintained across two generations, indicating the genetic stability of rhBMP2m gene knock-in at the αAmy3 intron 1 locus. Additionally, the rice cell-derived rhBMP2m proteins were found to be glycosylated, capable of dimer formation, and bioactive. Our results indicate that the endogenous rice αAmy3 promoter-signal peptide-based expression system is an effective strategy for producing bioactive pharmaceutical proteins. KEY POINTS: • The endogenous αAmy3 promoter-based expression system enhanced the yield of BMP2 • The increased yield of BMP2 accounted for 1.03% of the total rice-soluble proteins • The rice-produced BMP2 showed glycosylation modifications, dimer formation, and bioactivity.


Assuntos
Oryza , Humanos , Oryza/genética , Proteína Morfogenética Óssea 2/genética , Íntrons , Proteínas Recombinantes/genética , Preparações Farmacêuticas
6.
Angew Chem Int Ed Engl ; 63(25): e202403220, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38622058

RESUMO

Nature has inspired scientists to fabricate adhesive materials for applications in many burgeoning areas. However, it is still a significant challenge to develop small-molecule adhesives with high-strength, low-temperature and recyclable properties, although these merits are of great interest in various aspects. Herein, we report a series of strong adhesives based on low-molecular-weight molecular solids driven by the terminal modification of ionic liquids (ILs) and subsequent supramolecular self-assembly. The emergence of high strength and liquid-to-solid transitions for these supramolecular aggregates relies on modifying IL with a high melting point motif and enriching the types of noncovalent interactions in the original ILs. Using this strategy, we demonstrate that our IL-based molecular solids can efficiently obtain a high adhesion strength (up to 8.95 MPa). Importantly, we elucidate the mechanism underlying the reversible and strong adhesion enabled by monomer-to-polymer transitions. These fundamental findings provide guidance for the design of high-performance supramolecular adhesive materials.

7.
Angew Chem Int Ed Engl ; 63(21): e202400531, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38546292

RESUMO

Stress response, an intricate and autonomously coordinated reaction in living organisms, holds a reversible, multi-path, and multi-state nature. However, existing stimuli-responsive materials often exhibit single-step and monotonous reactions due to the limited integration of structural components. Inspired by the cooperative interplay of extensor and flexor cells within Mimosa's pulvini, we present a hydrogel with differentiated hydrogen-bonding (H-bonding) networks designed to enable the biological stress response. Weak H-bonding domains resemble flexor cells, confined within a hydrophobic network stabilized by strong H-bonding clusters (acting like extensor cells). Under external force, strong H-bonding clusters are disrupted, facilitating water diffusion from the bottom layer and enabling transient expansion pressure gradient along the thickness direction. Subsequently, water diffuses upward, gradually equalizing the pressure, while weak H-bonding domains undergo cooperative elastic deformation. Consequently, the hydrogel autonomously undergoes a sequence of reversible and pluralistic motion responses, similar to Mimosa's touch-triggered stress response. Intriguingly, it exhibits stress-dependent color shifts under polarized light, highlighting its potential for applications in time-sensitive "double-lock" information encryption systems. This work achieves the coordinated stress response inspired by natural tissues using a simple hydrogel, paving the way for substantial advancements in the development of intelligent soft robots.


Assuntos
Hidrogéis , Ligação de Hidrogênio , Hidrogéis/química , Interações Hidrofóbicas e Hidrofílicas
8.
Nano Lett ; 22(7): 3077-3086, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35343706

RESUMO

Highly permselective and durable membranes are desirable for massive separation applications. However, currently most membranes prepared using nonsolvent-induced phase separation (NIPS) suffer from low permeability and a high fouling tendency due to the great challenges in a rational design and also practical approach for membrane optimization. Inspired by the natural Murray network from vascular plants, we developed a hierarchical membrane via a straightforward yet robust strategy, using isocyanate as a multifunctional additive. Thanks to the integrated functions of a phase separation regulator, blowing agent, cross-linker, and functionalization anchor of isocyanate, our strategy is featured as a perfect combination of a phase separation and chemical reaction, and it enables synchronous engineering of the membrane hierarchy on porosity and components. The representative membrane exhibits superior water permeance (334 L/m2·h·bar), protein retention (>98%), and antifouling ability (flux recover ratio ∼ 98%). This work highlights a versatile path for pursuing a highly enhanced performance of NIPS-made membranes, from the fancy perspective of Murray bionics.


Assuntos
Membranas Artificiais , Ultrafiltração , Biomimética , Isocianatos , Porosidade
9.
Angew Chem Int Ed Engl ; 62(1): e202215060, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36344437

RESUMO

Advanced aqueous batteries are promising for next generation flexible devices owing to the high safety, yet still requiring better cycling stability and high capacities in wide temperature range. Herein, a polymeric acid hydrogel electrolyte (PAGE) with 3 M Zn(ClO4 )2 was fabricated for high performance Zn/polyaniline (PANI) batteries. With PAGE, even at -35 °C the Zn/Zn symmetrical battery can keep stable for more than 1 500 h under 2 mA cm-2 , and the Zn/PANI battery can provide ultra-high stable specific capacity of 79.6 mAh g-1 for more than 70 000 cycles at 15 A g-1 . This can be mainly ascribed to the -SO3 - H+ function group in PAGE. It can generate constant protons and guide the (002) plane formation to accelerate the PANI redox reaction kinetics, increase the specific capacity, and suppress the side reaction and dendrites. This proton-supplying strategy by polymeric acid hydrogel may further propel the development of high performance aqueous batteries.

10.
Angew Chem Int Ed Engl ; 62(31): e202307271, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37334981

RESUMO

Aqueous zinc (Zn) ion batteries are attractive for next generation batteries with high safety, yet their applications are still hindered by the uncontrollable dendrite formation and side reactions on Zn anode. Here, a polyzwitterion protective layer (PZIL) was engineered by polymerizing 2-methacryloyloxyethyl phosphorylcholine (MPC) in carboxymethyl chitosan (CMCS), which renders the following merits: the choline groups of MPC can preferentially adsorb onto Zn metal to avoid side reactions; the charged phosphate groups chelate with Zn2+ to regulate the solvation structure, further improving side reaction inhibition; the Hofmeister effect between ZnSO4 and CMCS can enhance the interfacial contact during electrochemical characterization. Consequently, the symmetrical Zn battery with PZIL can keep stable for more than 1000 hours under the ultra-high current density of 40 mA cm-2 . The PZIL confers the Zn/MnO2 full battery and Zn/active carbon (AC) capacitor with stable cycling performance under high current density.

11.
Angew Chem Int Ed Engl ; 62(51): e202314456, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37929923

RESUMO

The parasitic side reaction on Zn anode is the key issue which hinders the development of aqueous Zn-based energy storage systems on power-grid applications. Here, a polymer additive (PMCNA) engineered by copolymerizing 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-acryloyl glycinamide (NAGA) was employed to regulate the Zn deposition environment for satisfying side reaction inhibition performance during long-term cycling with high Zn utilization. The PMCNA can preferentially adsorb on Zn metal surface to form a uniform protective layer for effective water molecule repelling and side reaction resistance. In addition, the PMCNA can guide Zn nucleation and deposition along 002 plane for further side reaction and dendrite suppression. Consequently, the PMCNA additive can enable the Zn//Zn battery with an ultrahigh depth of discharge (DOD) of 90.0 % for over 420 h, the Zn//active carbon (AC) capacitor with long cycling lifespan, and the Zn//PANI battery with Zn utilization of 51.3 % at low N/P ratio of 2.6.

12.
Small ; 18(21): e2200829, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35344265

RESUMO

Layered MXene films have shown enormous potential for wide applications due to their high electrical conductivity and unique laminated microstructure. However, the intrinsic susceptibility to oxidation and the mechanical fragility of MXene films are the two major bottlenecks that prevent their widespread industrial applications. Here, a facile yet efficient assembly strategy is proposed to address these issues by increasing the alignment and compactness of MXene layers as well as strengthening the interlayer interactions. This method involves the gelation of MXene flakes with a multifunctional inorganic "mortar" polymer (ammonium polyphosphate, APP) followed by quasi-solid-state assembly enabled by a mechanical rolling process, by which the 3D gel network is transformed into 2D freestanding MXene films with unprecedented flake alignment and compactness. Besides, due to the multiple molecular-level interactions (hydrogen bonding, coordination bonding, and electrostatic force) between APP and MXene flakes, the resultant MXene-APP film (MAF) displays high mechanical strength (286.4 ± 20.3 MPa) and excellent electrical conductivity (8012.4 ± 325.6 S cm-1 ), along with remarkable environmental stability. As an application demonstration, MAF exhibits outstanding electromagnetic interference shielding effectiveness with long-term durability, highlighting the great potential of this gelation-assisted assembly strategy in fabricating large-area, high-performance MXene films for diverse real-world applications.

13.
Hu Li Za Zhi ; 69(5): 68-85, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36127760

RESUMO

BACKGROUND: Few of the interventions currently available for family caregivers (FCGs) of persons with dementia (PWDs) with long-term follow-ups have a grounding in theory and incorporate multicomponent case management formats. PURPOSE: Based on Pearlin's Caregiving and Stress Process model, this study was developed to examine the effectiveness of a family-centered case management program for PWDs with early to moderate dementia in terms of reducing PWDs behavioral problems and improve FCG outcomes, including distress, self-efficacy, depression, caregiver burden, and health-promoting behaviors. METHODS: This randomized, single-blind, parallel-controlled trial included 76 dyads of PWDs and their FCGs. The dyads were recruited from outpatient clinics at dementia centers in three district hospitals in northern Taiwan. The dyads were randomly assigned to the intervention group (IG, n = 39) and control group (CG, n = 37). The dyads in the IG received a four-month intervention with two home or clinic visits and two telephone interviews. The multi-component interventions provided assessment, education, consultations, support, and referrals to long-term care resources. The CG received routine care and two social phone calls. Data were collected upon enrollment (T0 = baseline) and at 4-,6-, and 12-months post-intervention (T1, T2, and T3, respectively). Generalized estimating equations were conducted to analyze the effects of the intervention. RESULTS: By controlling for the interaction between group and time, we made a comparison between IG and the CG. The results showed significant improvements from baseline measures in behavioral problems in the PWDs for mood, psychosis, and social engagement, and improvements in the FCGs for distress and self-efficacy for obtaining respite as well as for better control of distressing thoughts, feelings of depression, caregiver burden, and overall health promoting behaviors at T1 and T2 (p < 0.5). Significant improvements were also found in the IG for psychomotor regulation among PWDs and the self-efficacy of FCGs in managing the PWDs' disturbing behaviors and health promotion behaviors for nutrition at T1 (p < 0.5). There were no significant improvements in the outcome variables at T3. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Significant interactions between group and time were found at the 6-month assessment (T2) for improvements in problem behaviors of PWDs and depression, caregiver burden, and distress in the FCGs. Positive effects on self-efficacy and health promotion behaviors among the FCGs were also achieved. The results suggest that a multicomponent case management intervention should be referenced in dementia care policymaking for FCGs and PWDs.


Assuntos
Demência , Comportamento Problema , Cuidadores , Administração de Caso , Depressão/terapia , Promoção da Saúde , Humanos , Autoeficácia , Método Simples-Cego
14.
Angew Chem Int Ed Engl ; 61(34): e202204960, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35760748

RESUMO

Thermal stiffening materials that are naturally soft but adaptively self-strengthen upon heat are intriguing for load-bearing and self-protection applications at elevated temperatures. However, to simultaneously achieve high modulus change amplitude and high mechanical strength at the stiffened state remains challenging. Herein, entropy-mediated polymer-mineral cluster interactions are exploited to afford thermal stiffening hydrogels with a record-high storage modulus enhancement of 13 000 times covering a super wide regime from 1.3 kPa to 17 MPa. Such a dramatic thermal stiffening effect is ascribed to the transition from liquid-liquid to solid-liquid phase separations, and at the molecular level, driven by enhanced polymer-cluster interactions. The hydrogel is further processed into sheath-core fibers and smart fabrics, which demonstrate self-strengthening and self-powered sensing properties by co-weaving another liquid metal fiber as both the joule heater and triboelectric layer.

15.
Small ; 17(26): e2101220, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34105250

RESUMO

A smart ionic skin patch with on-demand detachable adhesion has been developed as human-machine interface for physiological signal monitoring. In spite of the multifunctions demonstrated by existing ionic skin, it is still difficult to distinguish different signals simultaneously. Moreover, the secondary damages to the tissues are often overlooked when the adhesive materials are removing from the wound. Herein, a multifunctional biomimetic hydrogel with temperature, mechanical, electrical, and pH response is developed. This hydrogel is designed by in situ polymerizing of hydrophilic anion monomers in a natural cationic polysaccharide to construct multifunctional biomimetic ionic channel. Due to the reversible physical cross-linked network and thermosensitivity, the mechanical properties, adhesion, and visual effect of the hydrogel can be tuned by changing hydrogen bonding density via phase transition, thus making it an excellent biosafe material for wearable device. The hydrogel is utilized as skin patch intended for monitoring physiological signals stimulated by physical and chemical changes involving pressure, temperature, pH value, and electrocardiograph. Especially, this ionic skin patch can recognize temperature change signals precisely either in broad or extremely narrow temperature range. This smart skin patch can even recognize the pressure and temperature signals in real time and differentiate the signals simultaneously.


Assuntos
Hidrogéis , Dispositivos Eletrônicos Vestíveis , Adesivos , Humanos , Monitorização Fisiológica , Temperatura
16.
Small ; 17(42): e2103195, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34528386

RESUMO

Aqueous Zn-ion batteries own great potential on next generation wearable batteries due to the high safety and low cost. However, the uncontrollable dendrites growth and the negligible subzero temperature performance impede the batteries practical applications. Herein, it is demonstrated that dimethyl sulfoxide (DMSO) is an effective additive in ZnSO4 electrolyte for side reactions and dendrites suppression by regulating the Zn-ion solvation structure and inducing the Zn2+ to form the more electrochemical stable (002) basal plane, via the higher absorption energy of DMSO with Zn2+ and (002) plane. Moreover, the stable reconstructed hydrogen bonds between DMSO and H2 O dramatically lower the freezing point of the electrolyte, which significantly increases the ionic conductivity and cycling performance of the aqueous batteries at subzero temperatures. As a consequence, the symmetrical Zn/Zn cell can be kept stable for more than 2100 h at 20 °C and 1200 h at -20 °C without dendrite and by-products formation. The Zn/MnO2 batteries can perform steadily for more than 3000 cycles at 20 °C and 300 cycles at -20 °C. This work provides a facile and feasible strategy on designing high performance and dendrite free aqueous Zn-ion batteries for various temperatures.


Assuntos
Compostos de Manganês , Óxidos , Dendritos , Eletrólitos , Temperatura , Zinco
17.
FASEB J ; 34(9): 12127-12146, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32686865

RESUMO

Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-ß peptide (Aß). The production of Aß is mediated by sequential proteolysis of amyloid precursor protein (APP) by ß- and γ-secretases, and has been implicated as the essential determinant of AD pathology. Previous studies have demonstrated that the level of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in the membrane may potentially modulate Aß production. Given that PI(4,5)P2 is produced by type 1 phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), we sought to determine whether the level of PIP5K type Iα (PIP5K1A) can affect production of Aß by modulating the lipid composition of the membrane. Using a HEK-derived cell line that constitutively expresses yellow fluorescent protein-tagged APP (APP-YFP), we demonstrated that overexpression of PIP5K1A results in significant enhancement of non-amyloidogenic APP processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted Aß. Consistently, cells overexpressing PIP5K1A exhibited a significant redistribution of APP-YFP from endosomal compartments to the cell surface. Our findings suggest that PIP5K1A may play a critical role in governing Aß production by modulating membrane distribution of APP, and as such, the pathway may be a valuable therapeutic target for AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Células HEK293 , Humanos , Fosfatidilinositol 4,5-Difosfato/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Ratos
18.
Proc Natl Acad Sci U S A ; 114(15): E3129-E3138, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28351972

RESUMO

Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer's disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to preferentially govern the proteostasis of APP-C99. Consistently, significantly elevated levels of ErbB2 were confirmed in the hippocampus of human AD brains. We then found that ErbB2 effectively suppressed autophagic flux by physically dissociating Beclin-1 from the Vps34-Vps15 complex independent of its kinase activity. Down-regulation of ErbB2 by CL-387,785 decreased the levels of C99 and secreted amyloid-ß in cellular, zebrafish, and mouse models of AD, through the activation of autophagy. Oral administration of an ErbB2-targeted CL-387,785 for 3 wk significantly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice. This work unveils a noncanonical function of ErbB2 in modulating autophagy and establishes ErbB2 as a therapeutic target for AD.


Assuntos
Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Autofagia , Encéfalo/patologia , Presenilina-1/metabolismo , Receptor ErbB-2/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Presenilina-1/genética , Proteostase , Receptor ErbB-2/genética , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
19.
Small ; 15(5): e1804975, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30589208

RESUMO

Despite the discovery of chromogenic-layered materials for decades of years, fabrication of colloidally stable monolayer organic 2D nanosheets in aqueous media with colorimetric responses is still challenging. Herein reported is the first solution synthesis of chromic monolayer nanosheets via the topochemical polymerization of self-assembled amphiphilic diacetylenes in aqueous media. The polydiacetylene (PDA) nanosheets are ≈3-4 nm thick in solution and only ≈1.9 nm thick in the dried state, while the lateral size can reach several micrometers. Moreover, the aqueous stability endows PDA nanosheets with excellent processability, which can further assemble into films via vacuum filtration or act as an ink for high-resolution inkjet printing. The filtrated films and printed patterns exhibit fully reversible blue-to-red thermochromism, and the film also displays an interesting reversible colorimetric transition in response to near-infrared light, which is not reported for other PDA-only systems. The present colloidal PDA nanosheets should represent a new kind of chromic organic 2D nanomaterials that may be applied as novel building blocks for developing intelligent hybrid materials and may also find diverse sensing, display and/or anticounterfeiting applications.

20.
Phys Chem Chem Phys ; 21(39): 21882-21889, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31552957

RESUMO

Amorphous calcium carbonate (ACC) is the most important intermediate phase in the nucleation/crystallization process of CaCO3, and thus the proper interpretation of how ACC transforms into final crystals at the molecular level is crucial to understand various biomineralization phenomena. Herein, we successfully monitored the moisture-induced crystallization process of ACC via in situ FTIR spectroscopy, which is very sensitive to the specific changes of the different vibrational modes of carbonates and water molecules. In combination with the tools of perturbation correlation moving window and two-dimensional correlation spectroscopy, it is found that the driving force of ACC crystallization is the fracture of hydrogen bonds formed by H2OCO32-. The bending vibrations of carbonate are more sensitive to moisture permeation than the stretching modes, and the whole crystallization process can be divided into three sequential stages, i.e., the hydrated ACC first loses its structural water and converts to the dehydrated ACC, which then gradually transforms into vaterite, followed by the final growth of vaterite crystals. Anhydrous ACC microdomains are found to be already existing in the as-prepared ACCs.

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