Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by ...focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.
An oxygen‐resistant refractory high‐entropy alloy is synthesized in microlattice or bulk form by 3D ink‐extrusion printing, interdiffusion, and silicide coating. Additive manufacturing of equiatomic ...HfNbTaTiZr is implemented by extruding inks containing hydride powders, de‐binding under H2, and sintering under vacuum. The sequential decomposition of hydride powders (HfH2+NbH+TaH0.5+TiH2+ZrH2) is followed by in situ X‐ray diffraction. Upon sintering at 1400 °C for 18 h, a nearly fully densified, equiatomic HfNbTaTiZr alloy is synthesized; on slow cooling, both α‐HCP and β‐BCC phases are formed, but on quenching, a metastable single β‐BCC phase is obtained. Printed and sintered HfNbTaTiZr alloys with ≈1 wt.% O shows excellent mechanical properties at high temperatures. Oxidation resistance is achieved by silicide coating via pack cementation. A small‐size lattice‐core sandwich is fabricated and tested with high‐temperature flames to demonstrate the versatility of this sequential approach (printing, sintering, and siliconizing) for high‐temperature, high‐stress applications of refractory high‐entropy alloys.
This work demonstrates that an oxygen‐sensitive refractory high‐entropy alloy (RHEA) can achieve architecture freedom and good oxidation resistance by a series of simple processing steps: i) 3D ink‐extrusion printing, ii) interdiffusion‐sintering, and iii) silicide coating. This robust route unlocks rapid prototyping of RHEA parts and is applicable to a large variety of possible alloy compositions.
Boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious ...inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent’s anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1β, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.
Development of film materials has been limited by the hardness-fatigue resistance trade-off. The purpose of the present study was to obtain films with a combination of both high hardness and strong ...fatigue resistance. To achieve this, CoCrFeMnNi high entropy alloy films (HEAFs) were fabricated with three different structures: amorphous, high-density nanotwinned crystal structure with twin spacings of 2.2–5.6 nm, and ultrahigh-density nanotwinned columnar grains with twin spacings of 1.2–2.5 nm. Nanoindentation with dynamic mechanical analysis was used to measure the hardness and perform the fatigue tests. While higher twin densities could dissipate more energy by detwinning during fatigue loading to enhance the fatigue resistance, twin spacings larger than and small than 2 nm could, respectively, result in hardening and softening. Our results showed a high hardness of ~9 GPa and fair fatigue resistance (~104 cycles) for both amorphous and high-density nanotwinned crystalline layers. For the ultrahigh-density nanotwinned columnar grain structure, a high hardness of ~8.5 GPa and an excellent fatigue resistance (~106 cycles) were obtained. The outstanding fatigue resistance and high hardness were attributed to the synergistic effect of strain hardening and detwinning of ultrahigh-density nanotwins. The results not only enable CoCrFeMnNi HEAFs with a predominant combination of hardness and fatigue resistance, but also shed light on a new perspective for overcoming the conflict between hardness and fatigue resistance in film materials for microelectromechanical applications.
•We fabricated high entropy alloy films with different structures containing nanotwins.•We used dynamic mechanical analyses to measure hardness and perform fatigue tests.•Nanotwins dissipate energy by detwinning under loading to enhance fatigue resistance.•Twin spacings larger and small than 2 nm could, respectively, yield hardening and softening.•Films with twin spacings spanning across 2 nm showed excellent hardness-fatigue resistance.
CoCrFeMnNiAlx (x = 0, 0.07, 0.3, 0.6, 1.0, 1.3) high-entropy alloy films (HEAFs) were processed by co-sputtering of CoCrFeMnNi alloy and Al targets. The effects of Al content on the microstructures ...and mechanical properties of HEAFs were studied. The XRD results indicated that the crystalline structure changed from the single face-centered cubic (FCC) phase for x = 0 and 0.07 to duplex FCC + body-centered cubic (BCC) phases for x = 0.3 and 0.6, and eventually, to a single BCC phase for x = 1.0 and 1.3, which agreed with the corresponding selected-area electron diffraction patterns. Also, nanotwins were observed in the FCC phase. Mechanical properties of films were studied using nanoindentation and micropillar compression tests. The hardness increased from 5.71 GPa at x = 0 to 8.74 GPa at x = 1.3. The compressive yield strength increased from 1.59 GPa to 3.73 GPa; however, the fracture strain decreased from 20.91% (no fracture) to 13.78% with the increasing Al content. Both nanotwins and BCC phase contributed to the strengthening effects for CoCrFeMnNiAlx HEAFs. Also, compared to the bulk CoCrFeMnNiAlx counterpart, the film exhibited much higher hardness and strength because of the much smaller grain size and the presence of nanotwins.
A well-defined co-catalyst system TiO2 nanotube-Au (core)-Pt (shell) was demonstrated to be the combination of the localized surface plasmon effect of gold and excellent proton reduction nature of ...platinum. Furthermore, surface engineering by the descending Fermi energies of gold and platinum was beneficial to electron transfer.
Although urinary tract infection (UTI) is a common perioperative complication among elderly patients with hip fracture, its incidence and effects are often underestimated. This study investigated the ...effects of severe UTI (S-UTI) on elderly patients with hip fracture and the risk factors for this condition. In this retrospective nationwide cohort study, we searched Taiwan's National Health Insurance Research Database from 2000 to 2012 for data on patients aged ≥ 50 years with hip fracture who underwent open reduction and internal fixation or hemiarthroplasty for comparison with healthy controls (i.e. individuals without hip fracture). The study and comparison cohorts were matched for age, sex, and index year at a 1:4 ratio. The incidence and hazard ratios of age, sex, and multiple comorbidities associated with S-UTI were calculated using Cox proportional hazard regression models. Among the 5774 and 23,096 patients in the study and comparison cohorts, the overall incidence of S-UTI per 100 person-years was 8.5 and 5.3, respectively. The risk of S-UTI was cumulative over time and higher in the study cohort than in the comparison cohort, particularly in those who were older, were female, or had comorbidities of cerebrovascular accident or chronic renal failure.
The phase evolution, microstructure and mechanical properties of CoCrFeMnNiTix (x = 0, 0.2, 0.4, 0.6, and 0.8 in molar ratio, denoted as Tix hereafter) high entropy alloy films (HEAFs) were studied ...in this work. The films were prepared by co-sputtering of CoCrFeMnNi alloy and Ti targets. Abundant nanotwins were observed in the Ti0 and Ti0.2 films and the crystalline structures of both films were identified to be a single FCC phase. In Ti0.4 and Ti0.6, the matrix exhibited an amorphous structure, and both the nanocrystalline grains and nanotwins were embedded in the amorphous matrix. With further addition of Ti, the Ti0.8 film transformed to an amorphous structure. As a result, there was a phase transition from a single FCC to an amorphous structure with the increasing Ti content. Furthermore, nanoindentation tests showed that the hardness of the films increased from 6.62 GPa in Ti0 to 8.99 GPa in Ti0.8. Micropillar compression tests showed that the fracture strain decreased from >19.42% (no fracture) to 7.78% with the increasing Ti content. The best mechanical properties in compression were observed in Ti0.4, and the compressive yield and fracture strengths were 2.82 and 4.44 GPa, respectively, with the fracture strain of 12.4%, which was achieved by a balanced amount of nanocrystalline grains in the amorphous matrix.
Display omitted
•We fabricated CoCrFeMnNiTix (x = 0–0.8) high entropy alloy films by co-sputtering.•Phase transition from single FCC to amorphous structure with increasing Ti content.•Increasing hardness and decreasing ductility with the increasing Ti content.•4.44 GPa compressive strength and 12.4% fracture strain achieved in CoCrFeMnNiTi0.4•Optimize mechanical properties with balanced nanocrystals in the amorphous matrix
Peripherin 2 (PRPH2) is a tetraspanin protein concentrated in the light-sensing cilium (called the outer segment) of the vertebrate photoreceptor. The mechanism underlying the ciliary targeting of ...PRPH2 and the etiology of cone dystrophy caused by PRPH2 mutations remain elusive. Here we show that the late endosome (LE) is the main waystation that critically sorts newly synthesized PRPH2 to the cilium. PRPH2 is expressed in the luminal membrane of the LE. We delineate multiple C-terminal motifs of PRPH2 that distinctively regulate its LE and ciliary targeting through ubiquitination and binding to ESCRT (Endosomal Sorting Complexes Required for Transport) component Hrs. Using the newly developed TetOn-inducible system in transfected male and female mouse cones
, we show that the entry of nascent PRPH2 into the cone outer segment can be blocked by either cone dystrophy-causing C-terminal mutations of PRPH2, or by short-term perturbation of the LE or recycling endosomal traffic. These findings open new avenues of research to explore the biological role of the LE in the biosynthetic pathway and the etiology of cone dystrophy caused by PRPH2 mutations and/or malfunctions of the LE.
Peripherin 2 (PRPH2) is a tetraspanin protein abundantly expressed in the light-sensing cilium, the outer segment, of the vertebrate photoreceptor. The mechanism underlying the ciliary transport of PRPH2 is unclear. The present study reveals a novel ciliary targeting pathway, in which the newly synthesized PRPH2 is first targeted to the lumen of the late endosome (LE) en route to the cilia. We deciphered the protein motifs and the machinery that regulates the LE trafficking of PRPH2. Using a novel TetOn-inducible system in transfected mouse cones, we showed that the LE pathway of PRPH2 is critical for its outer segment expression. A cone dystrophy-causing mutation impairs the LE and ciliary targeting of PRPH2, implicating the relevance of LE to cone/macular degenerative diseases.
Abstract
5NosoAE is a webserver that can be used for nosocomial bacterial analysis including the identification of similar strains based on antimicrobial resistance profiles (antibiogram) and the ...spatiotemporal distribution visualization and phylogenetic analysis of identified strains with similar antibiograms. The extensive use of antibiotics has caused many pathogenic bacteria to develop multiple drug resistance, resulting in clinical infection treatment challenges and posing a major threat to global public health. Relevant studies have investigated the key determinants of antimicrobial resistance in the whole-genome sequence of bacteria. However, a web server is currently not available for performing large-scale strain searches according to antimicrobial resistance profiles and visualizing epidemiological information including the spatiotemporal distribution, antibiogram heatmap, and phylogeny of identified strains. Here, we implemented these functions in the new server, referred to as 5NosoAE. This server accepts the genome sequence file in the FASTA format of five nosocomial bacteria, namely Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecium and Staphylococcus aureus for query. All visualizations are implemented in JavaScript and PHP. This server will be useful for physicians and epidemiologists involved in research on infectious disease. The 5NosoAE platform is available at https://nosoae.imst.nsysu.edu.tw.
Graphical Abstract
Graphical Abstract
5NosoAE is a web-based tool that allows users to perform large-scale strain searches according to antimicrobial resistance profiles and visualize epidemiological information including the spatiotemporal distribution, antibiogram heatmap, and phylogeny of identified strains.
PDF
