In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from ...nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on‐demand synthesis of RNA are engineered. An extracellular, enzyme‐activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life‐like cell mimics.
An artificial signaling pathway is engineered herein such that a synthetic cell responds to an external biochemical stimulus by the production of adenosine triphosphate and transcription. The importance of cellularity is highlighted and encapsulation enables production of RNA in biochemical mixtures that otherwise inhibit transcription.
•The rising damp in Unstabilized Rammed Earth (URE) structures has rarely been studied.•A validated numerical approach is used to investigate the rising damp in URE walls.•The results show that the ...rising damp decreases the mechanical strength of the wall.•The rising damp reduces the horizontal bearing capacity of the URE wall.
The effect of rising damp on the Thermal-hydro-mechanical (THM) behavior of Unstabilized Rammed Earth (URE) structures has been rarely studied in literature. To consider this effect, we use a validated theoretical framework implemented in a finite element code for the THM behavior of URE materials. The effect of rising damp is then investigated and compared with the same wall not influenced by the rising damp. The simulation results show that time plays a positive role on the THM properties of an URE wall because the evaporation process reduces the humidity, decreases the water content, increases the thermal insulation and improves the mechanical strength of the wall. In contrast, the rising damp plays an opposite role since it has a cooling effect on the wall temperature. The wall dries more quickly and the water also flows fast to the bottom side of the wall. Without rising damp, the horizontal bearing capacity increases 47% when the time passes from 7 days to 1825 days after construction, while this increase is only 10% with the rising damp. The decrease of thermal insulation resistance and hydraulic conductivity becomes less in the wall with the rising damp after five years.
Xeno‐nucleic acids (XNAs) are synthetic genetic polymers with improved biological stabilities and offer powerful molecular tools such as aptamers and catalysts. However, XNA application has been ...hindered by a very limited repertoire of tool enzymes, particularly those that enable de novo XNA synthesis. Here we report that terminal deoxynucleotide transferase (TdT) catalyzes untemplated threose nucleic acid (TNA) synthesis at the 3’ terminus of DNA oligonucleotide, resulting in DNA‐TNA chimera resistant to exonuclease digestion. Moreover, TdT‐catalyzed TNA extension supports one‐pot batch preparation of biostable chimeric oligonucleotides, which can be used directly as staple strands during self‐assembly of DNA origami nanostructures (DONs). Such TNA‐protected DONs show enhanced biological stability in the presence of exonuclease I, DNase I and fetal bovine serum. This work not only expands the available enzyme toolbox for XNA synthesis and manipulation, but also provides a promising approach to fabricate DONs with improved stability under the physiological condition.
Terminal deoxynucleotidyl transferase (TdT) accepts threose nucleic acid (TNA) nucleotide substrates, and catalyzes de novo synthesis of TNA on the 3’ ends of DNA oligonucleotides. The TNA extension protects DNAs from nuclease digestion, and the DNA‐TNA chimeras are used directly as staple strands in the self‐assembly of DNA origami nanostructures (DONs). The TNA‐shielded DONs are more biologically stable under the physiological environment.
Neutral oxygen evolution reaction (OER) with unique reactive environments exhibits extremely slow reaction kinetics, posing significant challenges in the design of catalysts. Herein, a built‐in ...electric field between the tungstate (Ni‐FeWO4) with adjustable work function and Lewis acid WO3 is elaborately constructed to regulate asymmetric interfacial electron distribution, which promotes electron accumulation of Fe sites in the tungstate. This decelerates the rapid dissolution of Fe under the OER potentials, thereby retaining the active hydroxyl oxide with the optimized OER reaction pathway. Meanwhile, Lewis acid WO3 enhances hydroxyl adsorption near the electrode surface to improve mass transfer. As expected, the optimized Ni‐FeWO4@WO3/NF self‐supporting electrode achieves a low overpotential of 235 mV at 10 mA cm−2 in neutral media and maintains stable operation for 200 h. Furthermore, the membrane electrode assembly constructed by such self‐supporting electrode exhibits robust stability for 250 h during neutral seawater electrolysis. This work deepens the understanding of the reconstruction of OER catalysts in neutral environments and paves the way for development of the energy conversion technologies.
A built‐in electric field between Ni‐FeWO4 and WO3 simultaneously achieves the electron‐rich state of the Fe sites in tungstate and improvement of the local reaction environment to suppress Fe leaching and accelerate mass transfer during neutral water oxidation, which endows the membrane electrode assembly constructed of Ni‐FeWO4@WO3/NF with low cell voltages and robust stability for neutral seawater electrolysis.
Aqueous zinc‐ion batteries are regarded as promising and efficient energy storage systems owing to remarkable safety and satisfactory capacity. Nevertheless, the instability of zinc metal anodes, ...characterized by issues such as dendrite growth and parasitic side reactions, poses a significant barrier to widespread applications. Herein, we address this challenge by designing a localized conjugated structure comprising a cyclic polyacrylonitrile polymer (CPANZ), induced by a Zn2+‐based Lewis acid (zinc trifluoromethylsulfonate) at a temperature of 120 °C. The CPANZ layer on the Zn anode, enriched with appropriate pyridine nitrogen‐rich groups (conjugated cyclic −C=N−), exhibits a notable affinity for Zn2+ with ample deposition sites. This zincophilic skeleton not only serves as a protective layer to guide the deposition of Zn2+ but also functions as proton channel blocker, regulating the proton flux to mitigate the hydrogen evolution. Additionally, the strong adhesion strength of the CPANZ layer guarantees its sustained protection to the Zn metal during long‐term cycling. As a result, the modified zinc electrode demonstrates long cycle life and high durability in both half‐cell and pouch cells. These findings present a feasible approach to designing high performance aqueous anodes by introducing a localized conjugated layer.
A polyacrylonitrile‐based zinc ion conductor (CPANZ) with a localized conjugated structure is induced and achieved at low temperature by Lewis acidic Zn(OTf)2. The CPANZ layer effectively accelerates the Zn2+ migration but restricts the H+ migration. Encouragingly, the chemical corrosion, hydrogen evolution reaction and other side reactions are significantly mitigated at the CPANZ@Zn anode and homogeneous Zn deposition/dissolution is guaranteed.
The chemical durability of perfluorosulfonic acid (PFSA) membranes is a topic of growing interest to meet Department of Energy (DOE) durability targets for heavy‐duty vehicle (HDV) applications. ...State‐of‐the‐art membranes like Nafion, rely on the use of cerium, heteropolyacids, and other inorganic additives to increase PFSA chemical durability. A less explored avenue for the oxidative stabilization of PFSA and hydrocarbon membranes is the use of organic antioxidants. No reversible organic antioxidant has been demonstrated to date which can enhance membrane lifetime by factors comparable to cerium. Here, ellagic acid (EA) is demonstrated as a promising radical scavenger for PFSA's. It is found that the incorporation of EA enhances the chemical durability of Nafion by 160%. EA, when incorporated with cerium as an electron donorenhances Nafion durability by at least 80% compared to a membrane incorporated with just cerium in DOE‐defined durability tests. EA is found to be reversible in acidic conditions like those of fuel cells and its reversibility could be further enhanced by the use of suitable co‐antioxidants.
Bio‐sourced antioxidant, ellagic acid is found to be highly reversible in the acidic conditions of hydrogen fuel cells. It enhances Nafion durability by 2.5 times when incorporated alone and at least 1.8 times compared to the state‐of‐the‐art when incorporated with cerium. Tethering ellagic acid to the Nafion side chain is ideal for high durability over a long period of operation.
With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these therapies rely on ex vivo viral transduction ...to induce permanent CAR expression in T cells, which contributes to high production costs and long‐term side effects. Thus, this work aims to develop an in vivo CAR T cell engineering platform to streamline production while using mRNA to induce transient, tunable CAR expression. Specifically, an ionizable lipid nanoparticle (LNP) is utilized as these platforms have demonstrated clinical success in nucleic acid delivery. Though LNPs often accumulate in the liver, the LNP platform used here achieves extrahepatic transfection with enhanced delivery to the spleen, and it is further modified via antibody conjugation (Ab‐LNPs) to target pan‐T cell markers. The in vivo evaluation of these Ab‐LNPs confirms that targeting is necessary for potent T cell transfection. When using these Ab‐LNPs for the delivery of CAR mRNA, antibody and dose‐dependent CAR expression and cytokine release are observed along with B cell depletion of up to 90%. In all, this work conjugates antibodies to LNPs with extrahepatic tropism, evaluates pan‐T cell markers, and develops Ab‐LNPs capable of generating functional CAR T cells in vivo.
Utilizing an ionizable lipid nanoparticle (LNP) with extrahepatic tropism, this work demonstrates in vivo T cell transfection for CAR T cell engineering. Antibody targeting against the CD3, CD5, and CD7 pan‐T cell markers is explored, and following a single intravenous injection, the CD3‐LNPs generate transient CAR+ T cells capable of up to 90% B cell depletion.
Azomethine imines, as a prominent class of 1,3‐dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral ...azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper‐ or chiral phosphoric acid catalyzed ring‐closure reactions of N′‐(2‐alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy‐induced peripheral neuropathy (CIPN). Remarkably, the (S)‐ and (R)‐atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry.
The synthesis of axially chiral azomethine imines through copper‐ or chiral phosphoric acid (CPA)‐catalyzed ring closure of N′‐(2‐alkynylbenzylidene)hydrazides is described, showing high efficiency, mild conditions, broad scope, and excellent enantioselectivity. Biological studies revealed the neuroprotective activity of the S product for dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin.
To lower the cost of additive manufacturing of metallic components, the goal of this work is to investigate and optimize a multi‐step process by material extrusion (MEX) of a polylactide filament ...loaded with bronze to remove the gas produced during the debinding and sintering steps. First, by adjusting the infill (10%, 50%, and 100%), and then by designing and constructing internal passages to aid in the expulsion of gases that occur during the debinding, a calibration cube is created. Additionally, the impact of the cooling period during the debinding is examined. To assess how the technique changes shape, sizes, and internal structure, all the samples are ultimately weighed, scanned, and cut. In order to reduce deformation occurred during the debinding and sintering gases, a new design method has been developed. The method consists of the generation of internal channels which connect the voids of the infill and allow gases to flow out through a central channel. As seen, samples with ejection channels and an intermediate infill (i.e., 50%) both exhibit better attributes.
In this study, an innovative manufacturing approach using bronze‐filled polylactide filament with a material extrusion (MEX) 3D printer is presented. By incorporating internal channels for gas expulsion, the debinding and sintering process is optimized, reducing component distortion. The investigation included 3D scans, SEM micrographs, and spectroscopic analysis. The results are encouraging and hold significance for low‐cost metal printing technologies.
N‐Trifluoromethylated organics may be applied in drug design, agrochemical synthesis, and materials science, among other areas. Yet, despite recent advances in the synthesis of aliphatic, cyclic and ...heterocyclic N‐trifluoromethyl compounds, no strategy based on trifluoromethyl nitrene has hitherto been explored. Here we describe the formation of triplet trifluoromethyl nitrene from azidotrifluoromethane, a stable and safe‐to‐use precursor, by visible light photocatalysis. The addition of CF3N to alkenes via biradical intermediates afforded previously unknown aziridines substituted with trifluoromethyl group on the nitrogen atom. The obtained aziridines were converted into either N‐trifluoromethylimidazolines, via formal 3+2 cycloaddition with nitriles, mediated by a Lewis acid, or into N‐trifluoromethylaldimines, via ring opening and aryl group migration mediated by a strong Brønsted acid. Our findings open new opportunities for the development of novel classes of N‐CF3 compounds with possible applications in the life sciences.
Iridium‐photocatalysed generation of triplet trifluoromethyl nitrene from CF3N3 is reported. The nitrene adds to alkenes to form N‐CF3‐aziridines. Their acid‐mediated 3+2 cycloaddition with nitriles to N‐CF3‐imidazolines and rearrangement to N‐CF3‐imines is investigated.
