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"Chen, Po"
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How to develop machine learning models for healthcare
Rapid progress in machine learning is enabling opportunities for improved clinical decision support. Importantly, however, developing, validating and implementing machine learning models for healthcare entail some particular considerations to increase the chances of eventually improving patient care.
Journal Article
Mechanical stretch induces hair regeneration through the alternative activation of macrophages
Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.
Mechanical stimulation is known to affect cell proliferation, differentiation, and regeneration. Here, the authors demonstrate that stretching mouse skin recruits macrophages and polarizes them into M2 cells that facilitate hair regeneration through the release of growth factors, including HGF and IGF-1
Journal Article
An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli , Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.
Journal Article
Overcoming the energy gap law in near-infrared OLEDs by exciton–vibration decoupling
The development of high-performance near-infrared organic light-emitting diodes is hindered by strong non-radiative processes as governed by the energy gap law. Here, we show that exciton delocalization, which serves to decouple the exciton band from highly vibrational ladders in the S0 ground state, can bring substantial enhancements in the photoluminescence quantum yield of emitters, bypassing the energy gap law. Experimental proof is provided by the design and synthesis of a series of new Pt(ii) complexes with a delocalization length of 5–9 molecules that emit at 866–960 nm with a photoluminescence quantum yield of 5–12% in solid films. The corresponding near-infrared organic light-emitting diodes emit light with a 930 nm peak wavelength and a high external quantum efficiency up to 2.14% and a radiance of 41.6 W sr−1 m−2. Both theoretical and experimental results confirm the exciton–vibration decoupling strategy, which should be broadly applicable to other well-aligned molecular solids.Pt(ii) complexes allow the fabrication of efficient near-infrared organic light-emitting diodes that operate beyond the 900 nm region.
Journal Article
Probing the active site in single-atom oxygen reduction catalysts via operando X-ray and electrochemical spectroscopy
Nonnoble metal catalysts are low-cost alternatives to Pt for the oxygen reduction reactions (ORRs), which have been studied for various applications in electrocatalytic systems. Among them, transition metal complexes, characterized by a redox-active single-metal-atom with biomimetic ligands, such as pyrolyzed cobalt–nitrogen–carbon (Co–N
x
/C), have attracted considerable attention. Therefore, we reported the ORR mechanism of pyrolyzed Vitamin B12 using operando X-ray absorption spectroscopy coupled with electrochemical impedance spectroscopy, which enables operando monitoring of the oxygen binding site on the metal center. Our results revealed the preferential adsorption of oxygen at the Co
2+
center, with end-on coordination forming a Co
2+
-oxo species. Furthermore, the charge transfer mechanism between the catalyst and reactant enables further Co–O species formation. These experimental findings, corroborated with first-principle calculations, provide insight into metal active-site geometry and structural evolution during ORR, which could be used for developing material design strategies for high-performance electrocatalysts for fuel cell applications.
Understanding active-site geometry and structural evolution during electrocatalysis is important for further development. Here the authors use operando X-ray absorption spectroscopy combined with electrochemical impedance spectroscopy to investigate single atom catalysts derived from Vitamin B12.
Journal Article
A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria
Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system—a contact-dependent DNA delivery nanomachine—we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations.
Cell adhesion molecules (CAMs) are key for programming bacterial cell-cell adhesion. By leveraging the transfer of selectable marker genes between bacterial cells, the authors present a method for discovering synthetic CAMs that target naturally occurring bacterial surface components.
Journal Article
Structural Biological Materials: Critical Mechanics-Materials Connections
Spider silk is extraordinarily strong, mollusk shells and bone are tough, and porcupine quills and feathers resist buckling. How are these notable properties achieved? The building blocks of the materials listed above are primarily minerals and biopolymers, mostly in combination; the first weak in tension and the second weak in compression. The intricate and ingenious hierarchical structures are responsible for the outstanding performance of each material. Toughness is conferred by the presence of controlled interfacial features (friction, hydrogen bonds, chain straightening and stretching); buckling resistance can be achieved by filling a slender column with a lightweight foam. Here, we present and interpret selected examples of these and other biological materials. Structural bio-inspired materials design makes use of the biological structures by inserting synthetic materials and processes that augment the structures' capability while retaining their essential features. In this Review, we explain this idea through some unusual concepts.
Journal Article
Engaging customers in value co-creation or co-destruction online
Purpose
This paper aims to develop a theoretical model to understand co-creation/co-destruction of value through customer engagement in online channels. It also investigates the contributing factors.
Design/methodology/approach
The qualitative approach uses the critical incidents technique to answer the research questions. The authors identify 350 critical incidents in which customers expressed online customer engagement-induced value co-creation or co-destruction experiences. The factors and resulting propositions are identified through data analysis. Data coding and analysis are facilitated by using MAXQDA 12.
Findings
Co-creation through positively valenced engagement behaviors may occur when customers are delighted, feel valued, experience reciprocity, receive organizational incentives, are solicited for feedback, can count on service recovery efforts and interact with helpful, empathetic, polite and responsive employees. Co-destruction through negatively valenced engagement behaviors emerges from rude employee behaviors, indifference, confrontation with company representatives, technological failure, the lack of complaint outlets and customers’ desire for revenge.
Practical implications
Selecting and training employees to be helpful, polite, responsive and empathetic toward online visitors can trigger co-creation. Communication between firms and customers should boost customer approval and delight. Organizations can offer incentives, reliable service delivery and a recovery design to stimulate visitor participation. Soliciting feedback requires sound technological support and direct communication links with visitors.
Originality/value
This study presents the conditions and framework contributing to the duality of customer engagement-induced co-creation and co-destruction values in online channels from the customer, organizational, employee, service design and technological perspectives. It also addresses how value is co-created or co-destructed through examples.
Journal Article
Observation of single-defect memristor in an MoS2 atomic sheet
Non-volatile resistive switching, also known as memristor
1
effect, where an electric field switches the resistance states of a two-terminal device, has emerged as an important concept in the development of high-density information storage, computing and reconfigurable systems
2
–
9
. The past decade has witnessed substantial advances in non-volatile resistive switching materials such as metal oxides and solid electrolytes. It was long believed that leakage currents would prevent the observation of this phenomenon for nanometre-thin insulating layers. However, the recent discovery of non-volatile resistive switching in two-dimensional monolayers of transition metal dichalcogenide
10
,
11
and hexagonal boron nitride
12
sandwich structures (also known as atomristors) has refuted this belief and added a new materials dimension owing to the benefits of size scaling
10
,
13
. Here we elucidate the origin of the switching mechanism in atomic sheets using monolayer MoS
2
as a model system. Atomistic imaging and spectroscopy reveal that metal substitution into a sulfur vacancy results in a non-volatile change in the resistance, which is corroborated by computational studies of defect structures and electronic states. These findings provide an atomistic understanding of non-volatile switching and open a new direction in precision defect engineering, down to a single defect, towards achieving the smallest memristor for applications in ultra-dense memory, neuromorphic computing and radio-frequency communication systems
2
,
3
,
11
.
A combination of atomistic imaging and spectroscopy reveals that metal substitution into a sulfur vacancy is the underlying mechanism for resistive switching in transition metal dichalcogenide monolayers.
Journal Article