The interface between molecules and electrodes has great impact on charge transport of molecular devices. Precisely manipulating the structure and electronic coupling of electrode-molecule interface at a molecular level is very challenging. Here, we develop new molecular junctions based on tetrathiafulvalene (TTF)-fused naphthalene diimide (NDI) molecules which are anchored to gold electrodes through direct TTF-Au contacts formed via Au-S bonding. These contacts enable highly efficient orbital hybridization of gold electrodes and the conducting π-channels, yielding strong electrode-molecule coupling and remarkably high conductivity in the junctions. By further introducing additional thiohexyl (SHe) anchors to the TTF units, we develop molecular wires with multiple binding sites and demonstrate reversibly switchable electrode-molecule contacts and junction conductance through mechanical control. These findings show a superb electrode-molecule interface and provide a new strategy for precisely tunning the conductance of molecular devices towards new functions. Though charge transport in molecular devices depend on the electrode-molecule interface, controlling the interface’s contact geometry remains a challenge. Here, the authors report molecular junctions featuring TTF-fused NDI molecules anchored to gold electrodes through direct TTF-Au contacts. Typically, terminal anchors are introduced to molecular bridges to form electrode-molecule contacts and modify the interfacial interactions and structures7. For instance, amines8, thioethers10, and pyridines11 are commonly used as anchors to bind to gold electrodes through dative interactions, while thiol12 and alkyne13 anchors have been used to form covalent gold–sulfur (Au–S) and gold–carbon (Au–S) contacts. It is worth noting that, besides the nature of the electrode-molecule contacts, the orbital overlap between anchors and molecular bridges is also a key factor in determining the interfacial electronic coupling strength. In general, a metal–anchor bond that aligns with conjugated orbitals of molecular bridges can provide efficient interfacial orbital mixing and facilitates charge transport. However, it is challenging to precisely control the electrode-molecule contact geometry in molecular devices, and the misalignment between the metal–anchor bond and the conducting channel introduces additional resistance that lowers the conductance of the device.Charge transport across electrode-molecule interface plays significant roles in determining the properties and functions of molecular electronic devices16, supramolecular chemistry18, and molecular machines20 due to its remarkable electron-donating ability and redox properties. TTF is also regarded as an important unit in molecular electronics since it was proposed as a building unit of the first theoretical model of the single molecular rectifier in 197424. Since then, several TTF or π-extended tetrathiafulvalene (exTTF)-based molecular wires have been prepared by incorporating TTF or exTTF active center into the molecular backbone. In these systems, additional terminal anchors (thiol or thioether) are required to connect the TTF or exTTF molecular bridge to the electrode28. Using these anchors, however, increases the length and flexibility of the molecules, hence leading to a lower conductance. Herein, we report new TTF-fused naphthalene diimide molecular wires that can bind to gold electrodes and form single-molecule junctions through direct TTF–Au coupling in which the sulfur atoms of TTF bind to gold electrodes to form the Au–S bonds. In these junctions, the Au–S bonds are nearly coplanar with conjugated molecular orbitals. This produces strong electronic coupling at the electrode-molecule interface, which further leads to remarkable high conductance of 10−2G0 over a transport length of ~1.5 nm. We further introduce additional thiohexyl anchors to the terminal TTF units by taking advantage of their chemical modification feasibility. We show that the electrode-molecule binding sites in these wires can be either TTF–Au or thiohexyl-Au modes (see below), and importantly these binding sites can be mechanically controlled in a reversible manner, yielding tunable interfacial electronic coupling and hence the conductance of the single-molecule devices. These findings demonstrate that TTF can act as both functional unit and anchor for constructing highly conducting molecular wires, and offering a new way of modulating interfacial properties of molecular devices through mechanical control.Tetrathiafulvalene (TTF) finds important applications in organic conducting materials29. These wires contain an electron acceptor naphthalene diimide (NDI) core, which is flanked with two TTF units and forms a conjugated electron donor–acceptor–donor (D–A–D) framework. Various terminal substituents are incorporated into TTF units to modulate the interaction between molecules with gold electrodes. Long alkyl side chains are introduced to improve their solubilities in organic solvents. The unique D–A–D structure facilitates electron delocalization across the molecular backbone and produces long wave-length absorptions and small HOMO-LUMO gaps, as demonstrated by ultraviolet-visible (UV-vis) absorption spectroscopy and cyclic voltammetry (CV) characterizations  log-binned histograms and two-dimensional 2D) conductance-displacement histograms without any data selection. Histograms for measurements at different biases are shown in Fig. D conduct1 in a similar environment. As can be seen from Supplementary Fig. To further explore the electrode-molecule interactions in these junctions, we measure the NDI based control molecule 34. The orbital overlap between the S lone pairs and gold electrodes enables the formation of σ donor–acceptor S–Au bond aligned with the conducting π channel. The partial charge transfer from TTF to Au at the molecule-electrode interface promotes the transition of TTF towards a more aromatic form, producing an aromatic stabilization effect39. Contrary to other thioether anchors10, such aromatic stabilization effect provides the additional driving force for forming stable S–Au contacts. This unique effect presented in TTF not only leads to a relatively strong contact between molecule and electrode but also enables a direct orbital hybridization between Au and the delocalized conducting π-channels of the entire NDITTF backbone, yielding a strong interfacial electronic coupling and high conductance.To understand the properties of single-NDITTF-MF junctions, we first perform density functional theory (DFT)-based calculations to examine its optimized molecular geometry and orbitals. Figure 42. The calculation details are shown in the We next turn to DFT calculations to better understand their conducting properties using the FHI-Aims package with a Perdew-Burke-Ernzerhof (PBE) exchange-correlation functionalcis and trans conformation. We see that Au–S bonds are nearly perpendicular to the molecular backbone in the optimized junction geometry. This contact geometry enables the mixing of the orbitals of gold and the delocalized molecular π-orbitals, facilitating charge transport across the single-molecule junctions. Figure G0) at the Fermi energy (EF). The isosurface plots of the transmitting eigenstate at EF show a strong hybridization between gold and the delocalized molecular orbitals  is still higher than most of the molecular wires shown in Table We find that the peak conductance (1D histogram) of the NDITTF-MF molecule obtained at off-resonant transport regime is much higher than that of other conjugated molecular wires with similar length Table  is sligh14. By taking advantage of this feature, we design and synthesize a new TTF derivative  and ~5 × 10−4G0 (Low_G)  Fig. . Figure _G) Fig. , suggestEF. This is consistent with what has been observed for the single-NDITTF-MF junctions. By contrast, much weaker couplings as reflected by the narrower resonance peaks are observed when forming junctions through terminal SHe–Au bonding. The decreased electrode-molecule coupling is attributed to the weakened orbital mixing of gold electrodes and the π orbital of the molecular backbone, which is always observed for molecular wires terminated with the similar thioether anchors54, and leads to a lower transmission at EF. This hence accounts for the measured lower conductance. It should be further noticed that the existence of two different conductance states in single-NDITTF-SHe junctions suggest that their conducting properties can be modulated through altering the electrode-molecule binding sites and hence the interfacial electronic coupling.To gain more insight of the transport properties, we calculate the molecular orbitals and transmission functions of single-NDITTF-SHe junctions with different binding scenarios Fig. –13. We fGiven the unique structure and conducting properties of the NDITTF-SHe, we turn to modified STM-BJ measurements to explore the mechanical tunability of the electrode-molecule coupling within individual single-NDITTF-SHe junctions Fig. . To do s57. Our findings reported here provide a new design for mechanical molecular switches building on strongly coupled systems.To further validate this binding site switching mechanism, we perform similar measurements for the control molecule NDITTF-MF without SHe anchors. The results shown in Supplementary Fig. In conclusion, we demonstrate TTF to be a unique anchor that can offer strong electrode-molecule electronic coupling which is further translated into remarkably high conductance of single-molecule junctions. By introducing additional thiohexyl anchors to the TTF unit, we develop molecular wires with multiple binding sites and achieve mechanically tunable conductivity through reversibly changing the Au–S binding sites as well as interfacial couplings. This work offers new strategies to precisely modulate the electrode-molecule coupling character and sheds light for designing new functional interfaces and molecular devices.Single-molecule conductance measurements were performed in ambient conditions and room temperature using a custom-built scanning tunneling microscope-break junction (STM-BJ) setup. During the STM-BJ measurements, we repeatably drive a gold STM tip in and out of contact with a gold substrate in 1,2,4-trichlorobenzene (TCB) solution of NDITTF molecules (0.01–0.1 mM). After the Au–Au point contact is broken, the molecule can bridge the two electrodes and form a single-molecule junction. We measure the conductance as a function of the tip-substrate displacement during this process. One-dimensional conductance histograms and the two-dimensional conductance histograms were constructed by compiling thousands of collected conductance traces.We carried out density functional theory (DFT) calculations using the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional implemented by the Fritz Haber Institute ab initio molecular simulation (FHI-aims) packages. All the long alkyl side chains in the molecules were replaced by methyl groups to simplify calculation process. We first optimized the geometries of molecules to find optimal molecular structures. We then attached single Au atoms to the S anchors at the two sides of the molecules. After optimizing the geometry, two Au pyramid cluster with 60 atoms were attached to the S anchors, replacing the Au atoms used for geometry optimization. The Landauer transmission across these junctions are finally calculated using the nonequilibrium Green’s function (NEGF) formalism. The Au–S binding energies are calculated with gold pyramid clusters containing 2–7 layers of Au atoms.Supplementary Information


Se) of the thermocell was achieved at high-temperatures operation. The Se of a redox couple of ferricyanide and ferrocyanide ([Fe(CN)6]3−/4−) reaches − 1.67 mV/K in a DES consisting of ethylene glycol and choline chloride. Spectroscopic analysis reveals that this is due to the strong interactions between the redox couple and the DES. Furthermore, the cell can operate over a wide temperature range of 135–165 °C. This result is a desired feature for waste-heat recovery applications.Deep eutectic solvent (DES) was applied to the solvent of thermocell and high Seebeck coefficient ( In particular, middle-temperature waste heat in the range of 100–200 °C is available in abundance from the industrial sector, yet it is often wasted without any effort at recovery2. Thermoelectric conversion is an attractive method for waste heat harvesting, and the use of thermocells is a promising option due to their high Seebeck coefficients (Se)3. Similar to the Se for solid-state thermoelectrical technologies, the Se of thermocells is defined as the potential difference generated across a cell with a temperature gradient. In liquid-based systems, such a temperature dependence is also related to the redox reaction entropy of a given redox couple, yielding the following relationship:ΔE is the open-circuit potential, ΔT is the temperature difference, ΔS is the partial molar entropy difference of the redox species (redox reaction entropy), n is the number of electrons in the reaction, and F is the Faraday constant5. Se is one of the key parameters that determines the figure-of-merit of a thermocell, ZT = SeTσ/κ, where σ is the electrical (or ionic) conductivity of the electrolyte, κ is the thermal conductivity, and T is the absolute temperature. The ZT value represents the efficiency of a thermocell and thus, high Se and σ combined with a low κ are imperative in the design of a liquid-based thermo-electrochemical system. In addition to these requirements, the thermocell electrolyte for middle-temperature heat recovery necessitates excellent thermal stability at temperatures as high as ca. 200 °C. For this reason, thermocell systems utilizing ionic liquids (ILs) or high-boiling point organic solvents, such as MPN, DMSO, and γ-butyrolactone has been developed13. These solvents were found to have high thermal stability and negligible volatility at that temperature, making them suitable for middle-temperature waste-heat harvesting15. Furthermore, the wide range of operating-temperature of these solvents allows a large temperature difference (ΔT) to be applied to the thermocell, leading to a high power performance of the cell.Approximately 60% of energy produced is lost as waste heatSe than their aqueous counterparts (Table ΔS). As shown in Eq.  as an electrolyte. DES is a eutectic mixture of organic salt and a hydrogen-bond donor  and ethylene glycol (EG). Ethaline was chosen due to its disorganized characteristic, which owes to the presence of the hydroxy constituent21. We envisioned that this characteristic corresponds to the low internal order of the ethaline DES, allowing a for large entropy change to arise and thus a high Se to be obtained. Furthermore, a previous computational study on ionic liquids predicts that small, symmetrical, unbranched cation and anion lead to an increase in Se value22. Considering that DES and ILs are comprised of similar species, we expect that the prediction mentioned above can be extrapolated to this DES system. Here, ethaline is constituted of relatively small and unbranched cation, Ch+, and hard base anion, Cl−, which would supposedly lead to a high Se. Importantly, the thermal stability of ethaline over a wide range (− 68 to 210 °C)19 would allow for the operation of thermocell at the desired middle-temperature range.In this work, we propose a novel thermocell system that displays both a high Snor Fig. . The melSe measurement of the ethaline thermocell was elaborated (detail of the experiment is shown in the Voc) of the cell plotted against temperature difference. The Se of the thermocell was estimated from the slope of this plot to be − 1.67 mV K−1 with 15 mM of [Fe(CN)6]3− and [Fe(CN)6]4−.Se of the ethaline thermocell can be attributed to the large entropy difference, specifically solvation entropy, between [Fe(CN)6]3− and [Fe(CN)6]4−. [Fe(CN)6]4− has a higher surface charge density compared to that of [Fe(CN)6]3−, which further regulates the orientation of solvent molecules24. The solvation effect of these redox species was investigated by FT-IR spectroscopy  of 22.5 cm−1 against [Fe(CN)6]3− with an FWHM of 9.8 cm−1. The broader peak corresponds to more substantial structural heterogeneity in the solvation environment of [Fe(CN)6]4−, which is originated from the stronger hydrogen bond interaction between the solute and the solvent24. This enhanced interaction, in turn, leads to a tightly-packed solvation shell surrounding [Fe(CN)6]4− than that of [Fe(CN)6]3−. As a result, a large entropy difference presents between the two species, which is reflected in the high Se of the ethaline thermocell.The high opy Fig. a. [Fe(CN6]4− and [Fe(CN)6]3− in water are 12.6 cm−1 and 7.4 cm−1, respectively  is inferior to that in ethaline (12.5 cm−1). The enhanced difference of FWHM shown in ethaline can be attributed to the exaggerated solvation interaction in ethaline compared to water, and thus the Se of [Fe(CN)6]3−/4− is higher in the former. This is in good agreement with the smaller difference of FWHM between [Fe(CN)6]4− and [Fe(CN)6]3−, (4.8 cm−1) in an ionic liquid, [C2mim][EtSO4] ely Fig. b. The diO4] Fig. c, which Se is shown in Fig. Se value of the ethaline thermocell shows a gradual decrease with increasing the concentration of solutes. The Se trend can be rationalized as an effect of increased electrostatic interaction as explained in the Debye–Hückel theory, where the Se is proportional to the square root of electrolyte concentration26. The Se trend observed in ethaline thermocell is similar to those observed in previously reported aqueous and ionic liquid thermocells27. However, the concentration dependency of Se was more significant in ethaline thermocell than that in aqueous thermocell 6]3−/4− concentration increases the number of H-bonds formed between ethaline and [Fe(CN)6]3−/4−. In contrast, a negligible shift was observed in the aqueous electrolyte 6]3−/4− undergoes more prominent changes with differing concentrations of the redox couple, which reflects the Se trend shown in Fig. The solvation environment of various concentrations of  and K4[Fe(CN)6] (1:1 in mol/mol) were dissolved into ethaline, and the electrolytes were mixed using a sonicator for ca. 3 h before use and heated above 150 °C before every measurement to ensure the removal of trace water. The solution was introduced into an H-shaped glass cell . The Se measurement was conducted above 100 °C, and so aluminum heating-blocks were used to control the temperatures of the cold and hot sides. Platinum electrodes  were immersed into both sides of the thermocell and were connected to a source meter (Keithley 2401) to measure the open-circuit voltage (Voc) of the cell. The temperature of the thermocell was monitored by a probe thermocouple sensor (AS ONE TM201). During the measurement, the hot side temperature was kept at approximately 165 °C. The temperature of the cold side was increased gradually, and the Voc was plotted against the temperature difference at which it was observed. The Se of the ethaline thermocell was estimated from the slope of the plot.Various concentrations of KSe measurements of the aqueous thermocell followed the same setup and method as those for the ethaline thermocell. Here, the cold side temperature is fixed at 10 °C (by using an ice water bath), and the hot side temperature is increased gradually to plot the Voc at different temperature differences. Similarly, the Se of the aqueous thermocell was estimated from the slope of the plot.The Se measurement, as shown above. The temperature difference between the two electrodes was kept at 29.7 °C, with the hot temperature set at approximately 165 °C and the cold temperature at 135.3 °C. The measurement was conducted by recording the current generated by various potential differences, namely Voc to zero. The current density was determined by dividing the recorded current values by the working area of the platinum electrode (52.62 mm2). Subsequently, the power density generated by the thermocell was calculated by multiplying the current density by the recorded voltage. This data was then plotted against voltage and the maximum power output could be determined.The power and current performance of the ethaline thermocell were evaluated using the same setup and instruments as that of the hot = 39.7 °C, Tcold = 10 °C). Other conditions  were identical to those described above.The power and current performance of the aqueous thermocell utilized the same setup as described for the ethaline thermocell. To maintain analogous experimental conditions to that of the ethaline thermocell, here the temperature difference was also kept at 29.7 °C (TSupplementary Information.


Health crises such as viral pandemics arise suddenly and require immediate actions and responses; others come to light more slowly and are more inconspicuous and intractable. An example of the latter is antimicrobial resistance (AMR), which was reported shortly after the introduction of the first effective antimicrobial agent and has been declared as one of the top ten global public health threats facing humanity by WHO in 2019.AMR occurs when microbes, such as bacteria, viruses, fungi, and parasites, adapt over time and no longer respond to drugs to which they were initially sensitive, making infections harder to treat and resulting in an increased risk of disease spread, and severe illness and death following routine medical procedures such as surgery. In 2019, the Interagency Coordination Group on Antimicrobial Resistance estimated that drug-resistant diseases are responsible for at least 700 000 deaths globally per year, a figure that could potentially increase to 10 million deaths globally per year by 2050.QualityPremiumscheme, which was introduced in 2015 to reward general practitioners for improvements in quality of care, including the reduction of inappropriate antibiotic prescribing in primary care. However, hospitals remain a key site for the transmission of antimicrobial-resistant bacteria, emphasising the importance of good hygiene and infection prevention and control protocols as well as evidence-based consideration of the appropriate prescribing of antimicrobials. Hospital inpatients are therefore at an increased risk of developing AMR compared with outpatients. Of note, according to WHO, people with a methicillin-resistant Staphylococcus aureus infection, which is primarily a hospital-acquired infection, are 64% more likely to die than people with drug-sensitive infections.Although AMR is a natural phenomenon, resistance develops more rapidly through the misuse and overuse of antimicrobial agents. Therefore, health-care workers play a pivotal role in preventing AMR. The English Surveillance Programme for Antimicrobial Utilisation and Resistance Report 2019 to 2020, published by Public Health England, noted that the total consumption of antibiotics in England decreased by 7•5% between 2015 and 2019. This decrease is likely attributable to an increased awareness of AMR by health-care professionals, as well as due to the effect of government monetary incentives such as the While the impact of AMR on human health has been widely documented, the misuse or overuse of antimicrobial agents in agriculture and farming is also a substantial concern. For farmers and the food industry, a lack of effective antimicrobial agents to treat sick animals adversely affects food production. Farmers face an additional risk due to their close contact with animals that might be colonised or infected with resistant bacteria. Furthermore, resistant bacteria from animals can be transferred to humans via the consumption of animal products that contain antibiotic-resistant bacteria. Another risk for human infection with resistant organisms can arise from the consumption of vegetables that have been treated with antimicrobial agents. While AMR in agriculture and farming poses a significant risk to human health and economic wellbeing, the Farming and Agriculture Organisation of the UN reports that only 118 countries collected data on the use of antimicrobials in animals between 2015 and 2017, and notably fewer produce data for plant agriculture, highlighting the need for improved reporting in this area.To try and address some of these concerns, the WHO Global Action Plan on AMR was launched in 2015 with the intention of optimising the use of antimicrobial agents, and to attract investment in the research and development of new agents; an area which has stalled in recent decades. The action plan calls for initiatives to be accessible in an affordable and equitable way to those in low-resource settings. The plan also highlights the need for an effective one health approach, involving multipronged initiatives and policies across human and veterinary medicine, agriculture, and the environment.The WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS), was introduced in 2015 to help accomplish the objectives of the WHO Global Action Plan on AMR, and promotes the standardisation of the collection and sharing of AMR surveillance data across the globe. The first GLASS report, published in 2018, included data on more than 500 000 infections from 22 countries. Since then, the number of countries participating in GLASS has increased to 109, of which 107 provide AMR data, and 17 measure antibiotic consumption. Setting up country-level surveillance of resistance and consumption is vital for understanding the impact of AMR and to reduce the spread of resistant pathogens. Another initiative is World Antimicrobial Awareness Week, which was celebrated on Nov 18–24, 2021, and is a yearly event organised by the Food and Agriculture Organization of the UN, the World Organisation for Animal Health, and WHO. The event aims to promote awareness on antimicrobial resistance and to prevent further spread of drug-resistant infections.Despite increased participation in WHO-led initiatives to combat AMR, and improvement in AMR surveillance systems in several countries, further AMR data are required to identify interventions that might slow resistance and to determine the effect of AMR on human health in different countries. Collaborative efforts between doctors, veterinarians, industry, and regulators are required, and all stakeholders should be aware of their vital role in preserving the effectiveness of antimicrobial agents so that these agents can be targeted to diseases where their use is appropriate. Treatment should also be stopped when no longer indicated. These efforts will help to ensure effective drugs are not lost from future patient management.


It is established that electron transmission through chiral molecules depends on the electron's spin. This phenomenon, termed the chiral‐induced spin selectivity (CISS), effect has been observed in chiral molecules, supramolecular structures, polymers, and metal‐organic films. Which spin is preferred in the transmission depends on the handedness of the system and the tunneling direction of the electrons. Molecular motors based on overcrowded alkenes show multiple inversions of helical chirality under light irradiation and thermal relaxation. The authors found here multistate switching of spin selectivity in electron transfer through first generation molecular motors based on the four accessible distinct helical configurations, measured by magnetic‐conductive atomic force microscopy. It is shown that the helical state dictates the molecular organization on the surface. The efficient spin polarization observed in the photostationary state of the right‐handed motor coupled with the modulation of spin selectivity through the controlled sequence of helical states, opens opportunities to tune spin selectivity on‐demand with high spatio‐temporal precision. An energetic analysis correlates the spin injection barrier with the extent of spin polarization. The efficiency of electrons transport through chiral systems depends on their spin. Hence, chiral molecules are spin filters. Controlling the molecules' chirality provides a way to define the spin polarization. This molecular machine performs unidirectional rotations, inverting handedness of the molecule and therefore the spin‐polarization at each stage of the rotary cycle. However, to date most of these organic spin‐filters are based on molecules with fixed handedness, therefore limiting the spin of the transported electrons to that defined by the molecular chirality. A major challenge is the development of switchable organic spin‐filters, capable of inversion of the spin polarization. This would allow for the construction of responsive spintronic devices and therefore represents a major step forward in the field of organic spintronics.The discovery of spin‐selective electron transport through chiral molecules, that is the chiral induced spin selectivity (CISS) effect, has laid a foundation for the development and construction of spin filters based entirely on organic materials. The rotary cycle of a typical motor comprises alternating photochemical and thermal isomerization steps, each involving inversion of the overall helical handedness of the molecule. Due to this unique chirality‐controlled motion, these molecules were exploited in a wide range of applications including photo‐switchable catalysts, responsive liquid crystals, and interfaces, biological systems and other hard and soft materials. Recently, studies on a donor‐acceptor functionalized second generation molecular motor revealed flipping of spin polarization of the tunnelled electrons upon inversion of motor handedness associated with the light‐induced isomerization.Overcrowded‐alkene based molecular motors comprise an exceptional class of molecular machines capable of performing unidirectional rotary motion fueled by light and heat stimuli.Figure  In contrast to their second‐generation counterparts, these compounds have four distinct chiral states that can be accessed in sequential manner in response to light and heat stimuli. Comparison of Raman spectroscopy data, acquired on drop‐casted and solution samples, demonstrated that these molecular motors undergo light and heat induced isomerization while deposited as thin films on gold substrates. The uniqueness of this system is that four states with distinct helical configurations can be interconverted non‐invasively with specific sequence (clockwise or counter‐clockwise). In addition, the carboxylic acid functionalities present a convenient handle for further functionalization and thus development of more sophisticated single‐molecule based switchable spin‐filters ‐‐E diastereoisomer.In this work, we demonstrate the first‐generation molecular motor scaffold acting as a light‐reconfigurable spin filter ‐E‐1( (right‐handed helix) to M,M)‐Z‐1( (left‐handed helix), to P,P)‐Z‐1( (right‐handed helix), to M,M)‐E‐1( (left‐handed helix) is shown in Figure  For thin films on Ni/Au substrates, AFM morphologies of ‐‐E‐1 ‐‐Z‐1 ‐‐E‐1 ‐‐Z‐1 reveals formation of chiral nanofibers.The first‐generation molecular motor used in this study was designed based on a 1 Figure  and ‐‐E‐1 or ‐‐Z‐1 isomers  or metastable E‐1 isomers (from Z isomer),  = 100.1 ± 0.4 kJ mol−1, t1/2 = 21 h for metastable Z‐1 to stable Z‐1 isomerization, and Δ‡G (20 °C) = 78 ± 6 kJ mol−1, t1/2 = 10 s for metastable E‐1 to stable E‐1 isomerization , as derived from Raman data recorded with a 500 mW 785 nm laser  > 100 kJ mol−1, which is the barrier for the metastable Z‐1 to stable Z‐1 isomerization in solution. This demonstrates that, motor 1 drop‐casted on a gold substrate operates as four state light‐ and heat‐reconfigurable chiroptical switch.Raman micro‐spectroscopy data recorded on the molecular motor drop‐casted on gold substrate ‐‐E‐1 and ‐‐Z‐1: the first forms a close packed layer and the second forms chiral nanofibers.We observed that in addition to the change in the molecular conformation upon exposure to UV light and heat, distinct organization of the molecules adsorbed on the surface Figure –f. This 2.4I‐V) curves obtained in the mc‐AFM measurements on films of left‐handed helical molecules ‐‐E and ‐‐Z  or down  along the sample normal. The applied magnetic field was 0.5 T. The insets present the positive quadrant of the I‐V curve in a semi‐log plot. Figure S,S)‐‐E‐1. In the initial ‐‐E‐1 ‐‐Z‐1 (PSS) ‐‐Z‐1 (THI) after a few days, as evidenced by reversal of the spin selectivity to the original preference for Hdown   = (IUP − IDOWN)/(IUP + IDOWN) × 100  when IUP and IDOWN are the currents measured for Hup or Hdown, respectively. The SP data obtained from Figure S,S)‐‐E from negative to positive and then negative spin polarization is associated with light and heat induced changes in the helicity of the deposited motors from  to  and  during the three step process constituting half of the rotary cycle  Figure  is metasn Figure . For thee Figure .S,S)‐‐Z‐1 isomer ‐‐Z‐1, ‐‐E‐1 (PSS) and of ‐‐E‐1 (THI), which show similar spin selectivity as was observed for the curves shown in Figure TableS,S)‐‐E‐1 or ‐‐Z‐1, and the sign of the SP is identical for each configuration  for the both molecules, showing that the helicity, either  or  dictates the sign of SP. We stress that the transformation from trans (E‐1) to cis (Z‐1) isomers with the same inherent handedness of the electronic π‐system  does not affect the spin selectivity. A unique feature of the motor based system is that starting with, e.g., enantiomer ‐‐1 a four‐step right‐handed (clockwise) rotary cycle is followed. This implies precise control over the sequence of the helicity change and consequently modulation of the spin polarization.To complete the cycle, the study was continued starting from pure  comparing initial configuration, PSS and THI for ‐‐E‐1 are +0.1, −0.3, and +0.2 V, respectively. For ‐‐Z‐1, these differences are +0.4, −0.2, and +0.3 V. These values are large compared to thermal energy at room temperature and similar to values obtained in other CISS studies. They are consistent with the significant spin polarization observed at room temperature.The insets of Figure I–V curves for the stable isomers with  helicity, i.e., ‐‐E‐1 ‐‐Z‐1  isomers, shown in Figure R,R)‐‐Z‐1 is opposite to that observed for the corresponding isomers of the configuration ‐‐Z‐1. The changes in the sign of SP ‐‐E‐1 or ‐‐Z‐1 follow the sequence positive to negative to positive, that is again reflecting the modulation of molecular helicity from  to  to , in accordance with the changes in the CD spectra ‐‐E‐1 and ‐‐Z‐1, is higher than for ‐‐E‐1 and ‐‐Z‐1. Suda et al. studied M‐helical second‐generation molecular motor species, finding their structure significantly different from the system studied here. Their reported value of the SP for the initial state is 43% at 1.9 V and 44% for the PSS. These SP values are very similar to our results on stable M‐helical motors. Table R,R)‐‐E‐1. Indeed, in this configuration also the spin polarization is by far the largest and is 96% ‐‐E‐1 and ‐‐Z‐1 systems are highly asymmetric, namely the current is much higher when the bias is positive than for negative biases ‐‐E‐1 is identical to the Initial ‐‐Z‐1 and vice versa) the asymmetry in the THI must originate from effects unrelated to the helicity of the molecules, for example supramolecular arrangement of the molecules on the substrate in both Initial and PSS states. Our data unequivocally show that given the proper supramolecular arrangement of the molecular motors on the substrates, nearly quantitative SP in the tunneled electrons can be achieved within these reconfigurable molecular machines.The present experiments reveal the effect of configurational change on the electron conduction and spin transport properties. There are several observations that may hint at the structure‐function relation in the studied systems. While the π–π interactions. Our topographic AFM measurements clearly indicate a dramatic change in the organization of the molecules on the surface, as a result of changing the molecular configuration. For these drop‐casted samples, the molecular orientation on the surface is not well defined, although likely at some of the helical molecules are oriented parallel to the surface, to favor the interactions of the π‐system with the substrate. It is remarkable that, despite all these variables, the spin filtering correlates so well with the changes in the solution CD spectra. The configuration, as well as the sequence of formation of the helical structures – and as a consequence the sign of SP – can be precisely controlled noninvasively with light. These findings indicate that the mechanism of the CISS effect depends on the intrinsic properties of the molecules and not on the details of the conduction path. Such properties include polarizability and its anisotropy and most notable the intrinsic helicity.For these experiments made on a film deposited on a surface, it is impossible to assess the role of intermolecular interaction on the results, namely to what extent the results presented relate to conduction through a single molecule or through some supramolecular structure that could consist of molecules forming 4In conclusion, this work presents the dependence of the spin selective conduction on structural changes of the molecular motors as a result of photoisomerization  followed by thermal relaxation (THI). Remarkably high spin selectivity was observed in the photostationary state mixture of isomers obtained by photoisomerization, as compared to the initial structures. Our results clearly show that each of the four states of the unidirectional rotary cycle is characterized by distinct differences in SP and the system can be used in multistage control over modulation of spin polarization with high sequence‐specificity. The data presented here provide guidelines for designing highly efficient molecular spin filters based on the helical overcrowded alkene structures, in which the photo‐generated isomers (PSS) are stabilized against thermal relaxation.5E‐1‐stable diastereomers, samples were irradiated at 312 nm at room temperature until no further changes were observed in the UV–vis spectrum and kept overnight in the dark at 40 °C to complete thermal isomerization. Starting from both Z‐1‐stable diastereomers, samples were irradiated at 312 nm at −20 °C and the progress was monitored using UV–vis absorption spectroscopy. Upon reaching photostationary state samples were quickly moved to a precooled (−15 °C) CD sample holder and a CD spectrum was recorded. For the thermal helix inversion samples were warmed to room temperature and kept in the dark for ≈2 h to ensure complete conversion.For the CD studies, solutions of tetrahydrofuran (THF) were degassed by sparging with Argon for ≈1 min in a 1 cm quartz cuvette equipped with the septum‐sealed screw cap. Starting from both E‐1 or Z‐1 (0.1 mg mL−1) were prepared in THF drop‐casted on gold substrates and left to dry under air. As prepared samples were irradiated on a microscope stage at 300 nm using M300F2 LED guided to the sample by optical fiber. Irradiations were carried for ≈3–4 min. for Z‐1 and ≈10 min. for E‐1. Spectra were processed with simple and adaptive baselines, normalized and averaged using Spectragryph software.For the Raman studies in the solid, solutions of either −1 molecular motor was dissolved in dry tetrahydrofuran (THF), drop‐casted onto the substrate and dried in a nitrogen glove box under dark. Deep UV (300 nm) Fiber‐Coupled LED, SMA, 350 mA, 320 µW (Min) was used to irradiate the samples for 10 min in a nitrogen glove box. AFM topographies were obtained by Bruker‐AFM MultiMode 8 with a silicon tip (Model AC240TS‐R3 from Oxford instruments). Magnetic field‐dependent I–V measurements were obtained with the probe in contact with the surface with a controlled force (8–10 nN). Cantilever B  of a platinum‐coated silicon tip from Micromasch (HQ:DPE‐XSC11) was used in the measurements. For each state, ≈80–100 I–V curves were recorded with a constant applied magnetic field of 0.5 T for each magnetic field orientation (field UP(Hup) and DOWN (Hdown)). These curves were plotted as a graph by OriginPro and analyzed by average multiple curves function.Substrates were made by sputtering a 120 nm layer of nickel, followed by an 8 nm layer of gold on top of a silicon wafer with a 2 µm thermal silicon oxide layer, with a 10 nm titanium adhesion layer. All surfaces were cleaned by first immersing in boiling acetone and then in ethanol for 10 min, followed by UV‐ozone cleaning for 15 min and a final incubation in warm ethanol for 40 min. 1mg mLThe authors declare no conflict of interest.Q.R.Z., W.D., and A.K.M. contributed equally to this work. W.D. synthesized molecules and performed CD and Raman studies. W.D. and C.L.F.B performed UV/Vis and NMR studies. Q.R.Z, F.T., G.H.H., and K.S. involved in sample preparation. Q.R.Z. and A.K.M. performed mc‐AFM measurements. Q.R.Z. and S.C. analyzed the data. Q.R.Z., S.C. and R.N and B.L.F. wrote the manuscript. B.L.F and R.N. conceived the experiments and guided the project.Supporting InformationClick here for additional data file.


Salmonella enterica to humans; there is also concern that strains can acquire resistance to antimicrobials in the farm environment. Here, whole-genome sequencing (WGS) was used to characterize Salmonella strains (n = 128) isolated from healthy dairy cattle and their associated environments on 13 New York State farms to assess the diversity and microevolution of this important pathogen at the level of the individual herd. Additionally, the accuracy and concordance of multiple in silico tools are assessed, including: (i) two in silico serotyping tools, (ii) combinations of five antimicrobial resistance (AMR) determinant detection tools and one to five AMR determinant databases, and (iii) one antimicrobial minimum inhibitory concentration (MIC) prediction tool. For the isolates sequenced here, in silico serotyping methods outperformed traditional serotyping and resolved all un-typable and/or ambiguous serotype assignments. Serotypes assigned in silico showed greater congruency with the Salmonella whole-genome phylogeny than traditional serotype assignments, and in silico methods showed high concordance (99% agreement). In silico AMR determinant detection methods additionally showed a high degree of concordance, regardless of the pipeline or database used . For AMR detection methods that relied exclusively on nucleotide BLAST, accuracy could be maximized by using a range of minimum nucleotide identity and coverage thresholds, with thresholds of 75% nucleotide identity and 50–60% coverage adequate for most pipeline/database combinations. In silico characterization of the microevolution and AMR dynamics of each of six serotype groups  revealed that some lineages were strongly associated with individual farms, while others were distributed across multiple farms. Numerous AMR determinant acquisition and loss events were identified, including the recent acquisition of cephalosporin resistance-conferring blaCMY- and blaCTX–M-type beta-lactamases. The results presented here provide high-resolution insight into the temporal dynamics of AMR Salmonella at the scale of the individual farm and highlight both the strengths and limitations of WGS in tracking zoonotic pathogens and their associated AMR determinants at the livestock-human interface.Livestock represent a possible reservoir for facilitating the transmission of the zoonotic foodborne pathogen  Salmonella enterica is estimated to be responsible for 1.35 million infections, 26,500 hospitalizations, and 420 deaths each year in the United States alone . In this study, 128 non-typhoidal S. enterica strains isolated from repeated sampling on 13 New York State dairy cattle farms between 2007 and 2009 were characterized using WGS. All strains were isolated from apparently healthy, subclinically infected bovine hosts, as well as the associated farm environment  to characterize  sources ; howeverironment . Using WSalmonella enterica isolates (n = 128) obtained from one of 13 dairy farms in New York State were selected to undergo WGS for this study  , and QUAST version 4.5  , and Fasd reads)  was usedd reads)  was usedsion 4.5  and the sion 4.5  were usesion 4.5  was usedsion 4.5 .Salmonella genomes (see section “Whole-Genome Sequencing and Data Pre-processing” above) underwent in silico serotyping using the command line implementations of (i) the Salmonella in silico Typing Resource (SISTR) version 1.0.2 (k-mer based workflow). Serotypes assigned using all three methods are available for all 128 isolates . To confirm that all serotype assignments were reasonable, a phylogeny was constructed using core single nucleotide polymorphisms (SNPs) detected in all Salmonella genomes in this study (see section “Reference-Free Single Nucleotide Polymorphism Identification and Phylogeny Construction” below).In addition to undergoing traditional serotyping in a laboratory setting  as described previously , all 128on 1.0.2  and (ii)on 1.0.2   ABRicate1 version 0.8  AMsion 0.8 , (iii) Asion 0.8 , (iv) BTsion 0.8 , and (v)sion 0.8 . Assemblsion 0.8  was usedsion 0.8 , (ii) thsion 0.8 , (iii) tsion 0.8 , and  prediction model for lmonella   using the Sensititre system  available at Cornell University’s Animal Health Diagnostic Center as described previously .All 128 eviously . A “trueIn silico Antimicrobial Resistance Determinant Detection”) were obtained from (i) Supplementary Table 4 of the AMRFinder validation paper on paper . An isolon paper . For eacon paper  in R veron paper  was usedon paper  by treatSalmonella SIR classification , predicted MIC values for 14 antimicrobials produced using PATRIC3 were used to predict the SIR status of each of the 128 Salmonella isolates using the same NARMS breakpoints used for phenotypic testing. Azithromycin MICs produced by PATRIC3 were excluded, as azithromycin was not among the 15 antimicrobials used here for phenotypic testing. The ability of PATRIC3 to predict amikacin resistance was also not evaluated, as amikacin is not among the antimicrobials queried by PATRIC3. A confusion matrix was constructed as described above, using predicted SIR classifications derived from predicted MIC values produced by PATRIC3 and NARMS breakpoints. Additionally, the deviation of raw MIC predictions produced by PATRIC3 (MICPATRIC3) from “true” raw MIC predictions produced using phenotypic testing (MICPhenotypic) in number of dilution factors (Ndilution factors) was assessed using the following equation:To assess the ability of the MIC prediction method implemented in PATRIC3 to predict where ln corresponds to the natural logarithm. For example: if PATRIC3 predicted an MIC value of 8 and the “true” MIC value obtained with phenotypic testing was 2, then ln(8/2)/ln(2) = 2; this means that the PATRIC3 prediction of 8 is +2 dilution factors away from the “true” MIC of 2 .n = 21) isolates possessed a phenotypic AMR SIR profile which was deemed to be highly incongruent with its predicted in silico AMR profile, regardless of the in silico pipeline/database used , which conferred multidrug resistance in closely related S. Newport isolates  as described above (see section “Prediction of Phenotypic Susceptible-Intermediate-Resistant Classifications Using in silico Methods”), with the exception of amikacin and kanamycin, as the contemporary panel did not include these antimicrobials  and are reported in the main manuscript . Original and updated MIC and SIR values for all 21 isolates are available in Minimum inhibitory concentration values obtained from re-testing these isolates were interpreted within NARMS breakpoints as described above . For a plasmid replicon to be considered present in a genome, minimum nucleotide BLAST (BLASTN)   identity(BLASTN) .Salmonella genomes sequenced in this study to 442 of the 445 Salmonella genomes described by Salmonella genomes, using the optimal k-mer size determined by Kchooser (k = 19). IQ-TREE version 1.6.10  were used as input for Roary version 3.12.0  serotype, (ii) farm, and (iii) isolation source . For each of the three grouping factors, the following three statistical tests were performed, using the gene presence/absence matrix produced by Roary, a Jaccard distance metric, and 10,000 permutations: (i) the permutest and betadisper functions in R’s vegan package  were usePotential clustering based on AMR gene presence/absence was additionally assessed for the same three grouping factors , using the presence and absence of AMR determinants detected by AMRFinderPlus as input . All steps were performed as described above, and a Bonferroni correction was used to correct for multiple comparisons.3 , the optimal ascertainment bias-aware nucleotide substitution model selected using ModelFinder, and 1,000 replicates of the UltraFast bootstrap approximation. The temporal structure of each resulting ML phylogeny was assessed using the on 1.5.1 .A tip-dated phylogeny was then constructed for each serotype using BEAST version 2.5.0 , 2019, uPRJNA756552. NCBI BioSample accession numbers for each individual isolate, as well as all associated metadata and genome quality statistics, are available in https://github.com/lmc297/zru_farms.Illumina reads are available for all isolates sequenced in this study under NCBI Bioproject Accession Salmonella strains isolated from healthy  dairy cattle (n = 39) and their associated farm environments (n = 89) on 13 different New York State farms underwent WGS (in silico using both (i) SISTR and (ii) SeqSero2  SISTR’s core-genome multi-locus sequence typing (cgMLST) approach and (ii) SeqSero2 were both highly congruent with the Salmonella whole-genome phylogeny . Among S. Kentucky (n = 36), a single incongruent isolate was observed (ENV_KENT_16_12-04-07_R8-0061), as SeqSero2 could not detect an O-antigen within the genome and was thus unable to assign this isolate to any serotype. This isolate was assigned a serotype of 8,20:-:z6 using traditional serotyping ; SISTR classified the isolate as S. Kentucky, and the isolate clustered among the S. Kentucky isolates sequenced in this study within the Salmonella whole-genome phylogeny  were considered, discrepancies were observed among traditional serotype assignments and both in silico methods , SISTR was unable to differentiate the two  differed between the two methods  was selected as the final serotype to be reported for each isolate. Nine of the 13 farms surveyed here harbored Salmonella, more than half of all isolates in this study  were classified as susceptible to all 15 antimicrobials tested, while 38 isolates (29.7%) were classified as resistant to two or more antimicrobials , a range of minimum percent nucleotide identity and coverage thresholds were additionally tested  < 1.25E-26; The performance of the PATRIC3 valuated . PATRIC3Salmonella isolates sequenced here, the Salmonella pan-genome was more similar within serotype and within farm than between serotype and between farm, respectively  and accounting for a larger proportion of the variance (PERMANOVA R2 = 0.93) than farms  = 1 for each; Fifteen GE types  were isoGE types . NotablySalmonella Anatum isolates from Farm 39 shared a common ancestor circa 2005 , although this node could not be reliably dated   tetracycline, (ii) streptomycin, or (iii) ceftiofur and sulfisoxazole; the streptomycin-resistant isolate additionally exhibited reduced susceptibility to chloramphenicol  and May 2007  was resistant to ampicillin, ceftiofur, and ceftriaxone, and possessed an IncN plasmid, macrolide resistance gene mph(A), and beta-lactamase blaCTX–M–1 (S. Meleagridis isolates from Farm 01 each exhibited reduced susceptibility to either (i) cefoxitin, sulfisoxazole, and tetracycline, or (ii) ceftiofur -Ib and APH(6)-Id , beta-lactamase blaCMY–2, sulfonamide resistance gene sul2, and tetracycline resistance gene tetA (S. Newport lineage circulating on each farm formed one of three separate clades (PP = 0.99–1.0) that evolved from a common ancestor that existed circa March/April 2004 -Ia, respectively -Ia and was kanamycin-susceptible . All but one Farm 35 S. Newport isolates were additionally resistant to chloramphenicol and possessed floR; BOV_NEWP_35_10-02-08_R8-2688 did not possess floR and was chloramphenicol-susceptible  methods had been used for serotype variant assignment. Additionally, the S. Typhimurium/S. Typhimurium Copenhagen isolates sequenced here showcased the most diverse AMR phenotypic profiles and AMR gene presence/absence profiles  shared a common ancestor that existed circa December 2007/January 2008 ; (ii) were all resistant to ampicillin, kanamycin, streptomycin, sulfisoxazole, and tetracycline, with reduced susceptibility to additional antimicrobials observed sporadically; (iii) all possessed replicons for IncA/C2, IncFIB(AP001918), and IncFII(s) plasmids; and (iv) all possessed streptomycin resistance genes aadA12, APH(3″)-Ib and APH(6)-Id , beta-lactamase blaTEM–1, and antiseptic resistance gene qacE delta 1, with other AMR/stress response genes present sporadically , some AMR traits may be associated with a fitness cost for a given organism . ConsequSalmonella strains isolated over a short time frame , the study detailed here reveals that sporadic acquisition and loss of acquired AMR genes can occur within closely related populations over a short timescale. One particularly notable observation is represented by multiple, independent acquisitions of the beta-lactamase blaCMY among S. Typhimurium and S. Typhimurium Copenhagen, as all blaCMY acquisition events within this serotype group were confined to the 2000s. blaCMY can confer resistance to cephalosporins, including (i) ceftriaxone, which has been used in human medicine since the early 1980s, and is used to treat invasive salmonellosis cases when fluoroquinolones cannot be used , and (ii) ceftiofur, which has been used in veterinary settings since the late 1980s to treat disease cases among dairy cattle and other animals  over a longer timeframe are needed to determine whether the AMR dynamics observed here are merely sporadic, or rather are indications of larger trends.Due to the global burden that AMR pathogens impose on the health of humans and animals, numerous agencies have called for improved monitoring of pathogens and their associated AMR determinants along the food supply chain . The stuSalmonella lineages  were found to vary in terms of the farm-specific signal they possessed; some lineages  were found to be strongly associated with a particular farm, while other lineages  were distributed across multiple farms. Multiple scenarios may explain the existence of Salmonella lineages distributed across multiple farms, including movement of livestock, humans, pets, and/or wildlife , two Salmonella Typhimurium clonal groups were present , each of which shared a common ancestor dated circa 2007. WGS data can be used to identify time frames in which Salmonella lineages may have emerged in a given farm or region, which could help pinpoint root causes .In the study detailed here, wildlife  or introSalmonella clones may persist on a given farm. This suggests that WGS databases covering isolates from a large number of farms could be used to develop initial hypotheses about farm sources of Salmonella strains. While such applications are tempting, it is crucial that these types of data are only used for initial hypothesis generation; rigorous, critical epidemiological investigations are essential before any conclusions regarding strain source are drawn.While the characterization of additional, larger strain sets from more geographically diverse farms is essential, our data suggest that specific Salmonella isolates to be classified into meaningful, evolutionary units. Serotype assignments are used to facilitate outbreak investigations and surveillance efforts, construct salmonellosis risk assessment frameworks, and inform food safety and public health policy and decision-making efforts . Notably, both in silico serotyping approaches outperformed traditional Salmonella serotyping for this data set. Serotypes assigned using SISTR’s cgMLST approach and/or SeqSero2 were congruent with the Salmonella whole-genome phylogeny and were able to resolve all un-typable, ambiguous, and incorrectly assigned serotypes  with serotype prediction accuracies of 94.8 and 88.2%, respectively  outperforms SISTR for prediction of monophasic variants. S. Typhimurium lineage. Among the bovine-associated Salmonella strains sequenced here, a combination of S. Typhimurium strains that possessed the O5 epitope, and those that did not  was observed. Importantly, SISTR was unable to differentiate S. Typhimurium from S. Typhimurium Copenhagen, while SeqSero2 could, as reported previously  improved in silico serotyping accuracy. Overall, the results provided here lend further support to the idea that in silico serotyping may eventually replace traditional serotyping as WGS becomes more widely used and accessible  combinations of five in silico AMR determinant detection pipelines  and one to five AMR determinant databases ; and (ii) an in silico MIC prediction tool .In addition to studying the microevolution and AMR dynamics of bovine n = 111) WGS-based study of AMR Salmonella observed similarly high rates of concordance among several in silico AMR determinant detection tools  in a single country (Canada) over an extremely short temporal range (December 2012–2013). Similarly, the study detailed here is not a formal benchmarking study, and it is essential that its numerous limitations are pointed out.Here, all AMR determinant detection pipelines and AMR determinant databases showed an extremely high degree of concordance; regardless of pipeline or database selection, all tools performed nearly identically on an SIR-prediction task relative to (i) “true” SIR classifications based on NARMS breakpoints and “true” MIC values obtained for a panel of 15 antimicrobials, and (ii) each other. A previous, small-scale  from a single source (dairy cattle and their surrounding farm environments) in a confined geographic area  isolated over a short temporal range (fewer than 2 years). While all isolates were “unique” , many isolates were highly similar at both the genomic and pan-genomic level , indicating that, in some cases, the same lineage was being sampled repeatedly over time. Consequently, this relatively miniscule sample is unrepresentative of AMR pathogens and, more specifically, Salmonella as a whole; readers should not infer the general superiority or inferiority of any AMR detection tool or database tested, and the results obtained here should not be extrapolated to external data sets.First and foremost, the study conducted here relied on WGS data from an extremely small sample of Salmonella tend to be less diverse than Salmonella isolated from humans . This is not particularly surprising; numerous studies have shown that the resistomes of bovine-associated m humans , as wellm humans . Further disease .Salmonella bovine resistome and bias toward antimicrobial-susceptible isolates have important implications for the AMR pipeline/database comparison conducted here. For this data set, stringent and conservative approaches are rewarded, as isolates that do not possess AMR determinants are more likely to be predicted to be susceptible. While it is possible that different AMR detection tools may perform better on WGS data from pathogens with more diverse resistomes, very few formal benchmarking studies of in silico AMR determinant detection tools currently exist  that can confer resistance to colistin, a last-resort antibiotic used to treat MDR and extensively drug resistant infections , the omission of critically important genes could be a disastrous flaw. Similar to our results, a large study  querying NARMS isolates belonging primarily to the S. enterica species  observed a high degree of concordance between NCBI’s AMRFinder tool and ResFinder   . Howeveratabase) .n = 128) and sparsity of AMR isolates available in this study limited the methods that could be used to formulate the AMR tool/database comparison. The approach used here was similar to the one used to validate the AMRFinder tool  apply to in silico MIC prediction as well; for example, when “intermediate” resistance predictions produced via PATRIC3 are re-classified as “susceptible” (as was done for the AMR determinant detection approaches used here), PATRIC3’s accuracy for this data set increases to 96.0% and is on par with all other AMR prediction methods tested here. Readers should thus interpret comparisons among these methods with caution.Classifying bacterial pathogens into discrete SIR groups using AMR determinant detection methods is challenging, as it requires users to have a great degree of prior knowledge regarding the AMR determinants that are detected, the antimicrobials of interest, and the pathogen being studied. PATRIC3’s MIC prediction tool  offers ain silico AMR characterization has remained elusive, as the few available benchmarking studies differ in terms of the tools tested, the AMR database(s) used, and the data set(s) chosen for benchmarking. Furthermore, the underlying WGS data can affect pipeline performance , but also the biology of the pathogen being studied . To assess the robustness of in silico AMR predictions, researchers may additionally consider employing multiple in silico AMR characterization tools and/or databases in combination, as well as testing various AMR gene detection thresholds.Benchmarking and validating AMR detection and prediction tools is notoriously challenging , and verformance . For exaformance , 2019. Tformance . Here, nin silico AMR characterization tools relative to gold-standard phenotypic methods are only as reliable as the phenotypic data they rely on. Previous studies of Salmonella that attempted to predict phenotypic AMR using in silico methods  was lower for this study (71.8–84.4%) than sensitivity estimates calculated in a study of MDR Salmonella that included bovine isolates from New York State (97.2%)  was reported to be phenotypically resistant to nine antimicrobials but did not possess any acquired AMR determinants known to produce this phenotypic AMR profile. A recent case study in which WGS and phenotypic methods were used to characterize Salmonella isolates from raw chicken identified numerous AMR genotype/phenotype discrepancies resulting in both false negative and false positive predictions for in silico methods . The possibility that several heteroresistant Salmonella populations were characterized here cannot be discounted, as isolates underwent phenotypic AMR characterization and WGS separately . Other biological phenomena, such as plasmid loss during storage or culturing, or unknown/undetected resistance genes or mutations, could also contribute to discrepancies  . As ment methods . In thisepancies . HoweverThe datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/LC designed and carried out all computational analyses. AB, AG, JS, KC, and RC collected, analyzed, and/or interpreted all microbiological data. LC and MW conceived the study and co-wrote the manuscript with input from all authors. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The Nobel Prize in Chemistry was awarded in 1987 and 2016 for research in supramolecular chemistry on the “development and use of molecules with structure-specific interactions of high selectivity” and the “design and production of molecular machines”, respectively. This confirmed the explosive development of supramolecular chemistry. In addition, attempts have been made in systems chemistry to embody the complex functions of living organisms as artificial non-equilibrium chemical systems, which have not received much attention in supramolecular chemistry. In this review, we explain recent developments in supramolecular chemistry through four categories: stimuli-responsiveness, time evolution, dissipative self-assembly, and hierarchical expression of functions. We discuss the development of non-equilibrium supramolecular systems, including the use of molecules with precisely designed properties, to achieve functions found in life as a hierarchical chemical system. The existence of strong forces acting between specific molecules and ions (intermolecular interactions) began to be recognized after Pedersen serendipitously discovered the unique physical properties of cyclic ethers (crown ethers) in 1967 , the devFirst, we introduce the response of supramolecular structures to stimuli. The gradual change in a system (molecular assembly) from an initial state to the final state by applying a stimulus  is a process of transitioning from one equilibrium state to the next (or steady state) and can be considered as a relaxation phenomenon. This simple non-equilibrium state has attracted interest since the early days of supramolecular chemistry as a function of the stimulus response. Second, we describe a time evolution system in which the supramolecular structure changes as the constituent molecules undergo molecular transformation during self-assembly. If the system is in equilibrium between the assembly and the monomer, the supramolecular structure may change via the monomer. Based on this compositional change, a system of supramolecular structures can exhibit a transition or crossover. Third, we explain that non-equilibrium systems involving multiple chemical reactions and chemical fuels  are present. Thus, behaviors such as the transient formation of supramolecular structures, spontaneous changes in size, and driving from dissipative processes appear. Finally, we will present examples of studies that involve inducing the self-propulsion of supramolecular structures and communication between structures using hierarchical chemical systems triggered by chemical reactions or by incorporating cascade reactions. These hierarchical systems are expected to result in the construction of lifelike supramolecular systems .There is a vast array of precise and efficient self-assembly processes involved in the fundamental role of DNA plays in living systems with its replication and translation functions. To mimic the functions of such biomolecules using simple synthetic molecules, supramolecular materials with functions that can be switched on and off in response to stimuli have been created. Here, we present examples of how the physical properties of supramolecular materials can be changed by external stimuli such as the preparation conditions of the molecular assembly, pH changes, and light irradiation. In particular, we explain the properties that have been achieved by designing the structure of molecules to enable them to be used as shape memory materials and storage and transport carriers .There have been many reports on supramolecular gels since their physical properties can be measured using a variety of methods, and their formation can be confirmed by the simple method of inversion in a test tube. Van Esch and Feringa suggested that supramolecular gels can be created based on strategic molecular design principles. Many supramolecular gels have been developed based on original molecular design guidelines for organic chemists . In the In particular, the self-healing ability  is an emergent function that appears through the skillful control of intermolecular interactions and is applied to various chemical products and medical materials ,19. The D,L-lactic acid) have different film thicknesses and can deform into stomatocytes (invaginated vesicles) and tubular vesicles, depending on both the composition and solvent used during preparation . Cy. Cy83]. The presence of chemical fuels  has been reported to cause the transient formation of supramolecular self-assemblies or spontaneous morphological changes in systems that incorporate multiple chemical reactions. Prins and co-workers used molecular recognition between the zinc complex of 1,4,7-triazacyclonane and the phosphate moiety of adenosine triphosphate (ATP) to design and synthesize a new amphiphilic molecule with the zinc complex of 1,4,7-triazacyclononane as the hydrophilic part  88]. Th. Th88]. Derivatives of oligopeptides with specific amino acid sequences self-assemble into fibrous structures that are insoluble in water. Prior to transient formation of this structure, Tena-Solsona et al. attempted the dehydration condensation of fatty acids with dipeptides in water, using a derivative of carbodiimide as fuel . The anhN-isopropylacrylamide) . F. F109]. 2O2, between droplets of liquid-liquid phase separation (coacervation) in aqueous media [Moreover, Mason et al. has reported the realization of chemical communication of water-soluble compounds, Hus media . Coacervus media ,112.In this review, we discuss new properties and dynamics of supramolecular self-assemblies, such as stimulus response, time evolution, dissipative structural changes, and the incorporation of nonlinear reactions at the molecular level. Incorporating such reaction systems into supramolecular self-assemblies will enable the induction of lifelike dynamics in systems far from equilibrium, which is one of the significant goals of systems chemistry . Of courIf non-equilibrium systems of supramolecular self-assemblies can be designed and experimentally created from molecular structures, it will be easier to control the functions expressed as outputs. This will also lead to a better understanding of the complex functions observed in life. Currently, the development process is based on a trial-and-error approach, in which the optimal structure is sought by synthesizing derivatives with slightly different molecular structures and evaluating their properties and functions. Recently, it has become possible to analyze the physical properties of molecular assemblies such as vesicles and liquid crystals using molecular simulations and to use the training data collected from these simulations to conduct machine learning to predict the physical properties of molecular self-assemblies based on their molecular structures. If a cycle of predicting the properties of molecules, incorporating them into molecular designs, synthesizing them, and evaluating the functions of the resulting molecular assemblies can be established, strategies for rational molecular design that are supported by theory can be implemented in systems chemistry. Such materials informatics methods are expected to become the core processes for the development of functional materials in near future.


A search of specific eponyms will reveal the frequency of usage within a medical specialty. While usage of eponyms can be studied by searching PubMed, manual searching can be time-consuming. As an alternative, we modified an existing Biopython method for searching PubMed. In this method, a list of disease eponyms is first manually collected in an Excel file. A Python script then creates permutations of the eponyms that might exist in the cited literature. These permutations include possessives  as well as various forms of combining multiple surnames. PubMed is then automatically searched for this permutated library of eponyms, and duplicate citations are removed. The final output file may then be sorted and enumerated by all the data fields which exist in PubMed. This method will enable rapid searching and characterization of eponyms for any specialty of medicine. This method is agnostic to the type of terms searched and can be generally applied to the medical literature including non-eponymous terms such as gene names and chemical compounds.  Specifications tableAn “eponym” is a person after which something is named, usually due to a major role in its invention, description, or discovery. Alternatively, “eponym” may refer to the thing itself as a shorthand for an “eponymous term”. In clinical medicine, eponyms (in the latter sense) describe diseases, procedures, methods, signs, and symptoms. Eponyms enter into usage for a variety of reasons including acknowledgment or honoring an individual for a discovery. A disease eponym may succinctly communicate the etiology, histopathology, and outcome of a disorder. A typical study of eponyms is performed manually by searching the literature for the usage of a single eponym across multiple publications over a period of time. Any study of eponyms is complicated by the proliferation of variant forms over time, all of which would need to be manually generated, individually searched and then reconciled. To address inefficiencies in this process, we present a method for automating the search of a group of eponyms across the entire literature database PubMed.Here we describe a method for automating PubMed searches for eponyms. This method uses custom Python scripts and modules from the Biopython package. Biopython is an open source package written in Python and C that provides bioinformatics tools in Python 1.Convert compound eponyms (with more that one name) separated by a space to be separated by a hyphen 2.Split each eponym into two parts: Name(s) and Term 3.Convert and remaining compound eponyms (with more than one name) to use hyphens as name separators (Python)4.Conversion of any eponyms with a possessive form to a non-possessive form (Python)A list of medical eponyms is required to begin the search. This list can be derived from textbooks, journal articles, or online compendia. To illustrate the method, a list of twenty-seven gastrointestinal medical eponyms (root eponyms) was manually collected from review articles The process above consists of first manually “cleaning up” the list of eponyms to convert compound eponyms where the names are separated only by a space to instead use a hyphen. This manual pre-processing is needed to distinguish between an eponym named after more than one person  and a multi-word surname (e.g. “Van Slyke”). Manual pre-processing is required for this step because automating this process would be exceedingly difficult and prone to error.Escherichia coli” would fall into this category as the eponym adds the Latin suffix “-ia”, which is used to form genus names, to Escherich, the name of the organism's discoverer. Keeping the term intact preserves the original term while preventing the generation of permutations (see Permutation of eponyms below), which would not make sense in this context.The second step consists of splitting each eponym in the list into two parts, the Name(s) and the Term. This is also a manual step because terms may consist of one or more words. Eponyms that use prepositional phrases as a form of possession are “inverted” (e.g. “Crypts of Lieberkuhn” to “Lieberkuhn Crypts”) as a natural consequence of this process. If the name is not readily separable from the term, the Name(s) field is left empty and the entire eponym is mapped to the Term. This situation usually arises because the eponym does not include the original proper name, but instead incorporates a modification of the original name. In our example data, “https://notepad-plus-plus.org/). The remainder of the processing is done by a Python script using the above CSV file as input. All possessive forms  are converted to their non-possessive equivalent. Finally, any remaining conjunctions between names  are replaced by hyphens. The fully standardized form of the eponym lists is written to a UTF-8-encoded CSV file that serves as input for the next step.Microsoft Excel  is used for the manual pre-processing, and the data is exported as a UTF-8-encoded CSV file. For use with Python, the BOM (byte order mark) is then stripped from the Excel-generated CSV using the “Convert to UTF-8” function in Notepad++ : “Term of Name(s)”To identify all occurrences of these eponyms, we then use a Python script to permute the standardized form of the eponym into an exhaustive list of variants. Where applicable, the following permutations are applied combinatorially:The number of variants produced depends on the number of names (n) in the eponym, the number of names ending in “s”, and if the final name in the eponym ends in an “s”. The number of variants generated (not including the standard eponym) is 0 (where n=0), 2 to 3 (where n=1), 9 to 15 (where n=2), or 14 to 32 (where n=3). See the Python script (permute_terms.py) for additional details. The permuted terms are saved in a UTF-8-encoded CSV file that serves as input for the next step.In our example dataset, the twenty-seven root eponyms produced a total of 116 permutations. In the examples provided, “Zenker Diverticulum” describes a type of disease structure. This is a simple eponym with a single referenced individual (“Zenker”) joined to an anatomic medical term (“Diverticulum”). In addition to the standardized version (“Zenker Diverticulum”), two additional variants were produced: “Zenker's Diverticulum” and “Diverticulum of Zenker.”possible variants. The range of permutations applied was based on our experience of how eponyms vary in actual usage. The ability to generate permutations is a key advantage to using this automated method to exhaustively search a database.An example of a more complex eponym is “Mallory-Weiss Tear”, which references two individuals. Permutation of this term results in 13 variants in addition to the standardized version . While most of these variations will return no results, the intention of our permutation method is to produce an exhaustive list of https://www.ncbi.nlm.nih.gov/books/NBK25499/. Our script uses Biopython's Bio.Entrez.esearch and Bio.Entrez.efetch functions which correspond to the Entrez ESearch and EFetch E-utilities, respectively. Biopython does not provide a complete search implementation, but it significantly simplifies interactions with the E-utilities by handling communications, including sending requests, handling errors and retries, and parsing the returned data into Python objects. A simplified pseudocode version of our core search algorithm is shown in The list of permuted eponyms is then used as input to a custom Python script based on the Biopython package. Biopython's Bio.Entrez module provides a pythonic interface to the NCBI's Entrez Programming Utilities (“E-utilities” or “EUtils”), and the functions in Bio.Entrez map one-to-one to E-utilities web-based application programming interface (API). A detailed description of the Entrez E-utilities can be found here: https://meshb.nlm.nih.gov/record/ui?ui=D016672), and searching “Zenker Diverticulum"[MeSH Terms] returns 973 publications, accounting for many of these excess hits. It is not entirely clear where the remainder of the excess hits come from, but the PubMed search engine does apply additional search strategies to maximize the number of publications returned. While this can be helpful when performing general literature searches, it is not appropriate for studying eponyms. For this reason, we limit our searches to exact phrases in the Title OR Abstract fields of PubMed.While seemingly obvious, it is worth noting that a study of eponym usage in the literature hinges on identifying actual usage of the eponym itself and exclusion of related terms or synonyms. For this reason, PubMed searches must be limited to exact phrases and precise fields. For example, searching PubMed with the phrase “Zenker Diverticulum” (without quotes) returns 1316 hits, searching with the phrase “Zenker Diverticulum” (with quotes) returns 1023 hits, and searching with the phrase “Zenker Diverticulum” (with quotes) and limiting the search to the Title OR Abstract fields returns only 159 hits (search date: 11/7/2020). This not-inconsiderable discrepancy is easily explainable as a side effect of how PubMed conducts searches Even searches for exact phrases in Titles OR Abstracts can produce spurious results if the exact phrase is not found. In these instances, PubMed will broaden the search by (1) breaking up the quoted phrase into individual words joined by “AND” then (2) progressively dropping words from the search. This can result in very misleading results, especially when combined with our process of permutation, which frequently generates variants that produce no hits. For example, querying ESearch with “Mallory-Weiss Tear”[Title/Abstract] yields 154 hits, but the search for the permutation “Mallory-Weiss' Tear"[Title/Abstract] returns 33,071 hits. Examining the returned data for the latter query reveals that the “QueryTranslation” field is “Tear[Title/Abstract]”, indicating that PubMed has returned results for a translated query instead of the original query. Obviously, a common term like “tear” is going to produce many unrelated results. To prevent this from occurring, our method checks to see if the returned data includes a 'WarningList' with the “QuotedPhraseNotFound” warning. This flag is returned by the EUtilities API when the exact quoted phrase is not found. In these cases, the “Query Translation” does not match the original search query, and we ignore these results as indicated in the Algorithm.Our search method, embodied by the “pubmed_search_to_csv.py” script, uses Biopython's Bio.Entrez.esearch and Bio.Entrez.efetch functions. The esearch function takes several parameters, including the database (‘pubmed’), the term (the permuted eponym), and the field (‘title/abstract’). It also takes additional parameters related to how the results should be returned. Of these, retmax sets the maximum number of results (PMIDs) to be returned by the query, and retstart sets the sequential index of the first PMID to be returned. These parameters correspond directly to parameters passed to the Eutilities API. Entrez imposes a limit of 100,000 PMIDs returned by a single query, so retmax has a maximum value of 100,000. To retrieve more than 100,000 PMIDs, our method submits multiple esearch requests while incrementing the value of retstart. The PMIDs returned by esearch are collected in a Python list, and the efetch function is then used to retrieve details for the papers represented by the PMIDs. Like esearch, efetch imposes a limit on the number of results it will return. In this case, efetch will return details for up to 10,000 PMIDs per request. To retrieve more than 10,000 PMIDs, our method submits multiple efetch requests by breaking them into sub-lists of PMIDs up to a maximum length of 10,000 (“chunks”). We request the return data as text in the MEDLINE format, then store several pieces of data for each result, including PubMed ID (“PMID”), journal title (“JT”), and date of publication (“DP). The data is then saved to two results files: “term_results.csv” is a CSV file with summary data representing one permuted term per row; “pmid_results.csv” is a CSV file containing all the hits returned by Entrez, with one PMID per row. Note that the “pmid_results.csv” file may contain duplicate PMIDs within a given root term if the same PMID was matched by more than one permutation of the term. We use an additional script to remove these duplicates, and the de-duplicated version of the “pmid_results.csv” file is used to determine the combined PMID counts for a given eponym.We validated our method by querying PubMed on 11/4/2020 for 27 terms . One datFor Zenker Diverticulum, the root eponym has 159 citations, and the permutated term Zenker's Diverticulum has 722 citations. For Mallory-Weiss Tear, the permutations did not additional citations to a search of the root term (n=154). Interestingly, the permutation using “of” is infrequently used for these 27 root terms. Twenty-one of the root eponyms had no citations using the “of” possessive; however, there were 6 eponyms with the “of” possessive form that had citations: Diverticulum of Meckel, Crypts of Lieberkuhn, Sphincter of Oddi, Ampulla of Vater, Duct of Wirsung, Duct of Santorini. In total, the search of the permutated eponyms resulted in 386,714 citations after the removal of duplicate citations. The most frequent citation was for Escherichia coli  and the least frequent was for Rigler Sign (n=17).In addition to enumerating the total citations, other data fields within PubMed can be used to characterize the eponyms. For example, the publication year ranges from 1876 to 2021 (some publications in the 2020 search are indexed for 2021 publication). In 1876, the single eponym usage from this set is Meckel Diverticulum which was in the Journal of Anatomy and Physiology. Over time, the number of citations for these 27 terms has increased consistently, reaching 14,336 citations in 2020; the 2020 assessment is an incomplete year (January to October) but is higher than the full calendar year 2019 which had 13,119 citations.The dynamic usage of eponyms is demonstrated with Kaposi Sarcoma which had citations dramatically increased in the 1980s and 1990s with a peak of 468 citations in 1997 followed by a general decline to 357 citations in 2019, the last complete year analyzed. In comparison, the eponym Chagas Disease had consistent growth from 5 citations in 1945 to a peak of 634 citations in 2018.https://pubmed.ncbi.nlm.nih.gov/). All permuted terms were searched and the number of search hits was recorded for each exact phrase. To ensure that the exact term was matched, the search string was enclosed in quotation marks, and the search was limited to the Title and Abstract fields using PubMed's search syntax (“[Title/Abstract]”). For example, here are the search strings used for the “Zenker Diverticulum” permutations: “Zenker Diverticulum”[Title/Abstract]; “Zenker's Diverticulum”[Title/Abstract]; “Diverticulum of Zenker”[Title/Abstract].The method was validated by a manual search of PubMed using the web-based search interface  an exhaustive full text search of journals for eponyms would be nigh unachievable. Additionally, access to the full text of many journal articles is restricted based on subscriptions. The methods, as presented here, can be used to select from PubMed a subset of key journals for additional manual exploration at the full text level. However, with minor modifications, this method may be applicable for full text searching of databases that include the full text of open access articles  to further enhance the technique.Studying eponym usage in the literature presents a unique set of challenges that differs from the usual goal of literature searches. As such, one must be careful and precise in how a tool like PubMed is used to obtain search results. We have presented a method for identifying eponym usage that automates the most tedious aspects of exhaustive searching for eponymous terms while addressing most of the pitfalls one is expected to encounter. It should be noted that while this method is designed to identify eponym usage in the textual data in PubMed (i.e. title and abstract), it cannot identify eponym usage elsewhere in the body of a paper. Currently, identifying eponyms in the full text of articles remains a tedious manual process that is highly dependent on the availability of adequate full text search tools provided by the journal itself. Given that there are approximately 30,000 journals cited in PubMed (None.


Mikania micrantha. The competitive performance of seven M. micrantha populations varying in their conspecific and heterospecific abundance were monitored in a greenhouse experiment, by manipulating soil biota (live and sterilized) and competition conditions . Our results showed that with increasing conspecific abundance and decreasing heterospecific abundance, (1) M. micrantha increased intraspecific competition tolerance and intra‐ vs. interspecific competitive ability but decreased interspecific competition tolerance; (2) M. micrantha increased tolerance of the negative soil biota effect; and (3) interspecific competition tolerance of M. micrantha was increasingly suppressed by the presence of soil biota, but intraspecific competition tolerance was less affected. These results highlight the importance of the soil biota effect on the evolution of competitive ability during the invasion process. To better control M. micrantha invasion, our results imply that introduction of competition‐tolerant native plants that align with conservation priorities may be effective where M. micrantha populations are long‐established and inferior in inter‐ vs. intraspecific competitive ability, whereas eradication may be effective where populations are newly invaded and fast‐growing.Understanding the shifts in competitive ability and its driving forces is key to predict the future of plant invasion. Changes in the competition environment and soil biota are two selective forces that impose remarkable influences on competitive ability. By far, evidence of the interactive effects of competition environment and soil biota on competitive ability of invasive species is rare. Here, we investigated their interactive effects using an invasive perennial vine,  Mikania micrantha. The results showed that M. micrantha evolved higher intra‐ vs. interspecific competitive ability during its invasion, and that soil biota likely mediated the evolutionary process. This work implies that introduction of competition‐tolerant native plants that align with conservation priorities into long established invaded sites may be effective to control the invasion of M. micrantha.This work investigated the interactive effects of competitive environment and soil biota on competitive ability in an invasive plant  We asked the following questions: (1) How is M. micrantha competitive performance related to its conspecific and heterospecific abundance? (2) What is the effect of soil biota on M. micrantha competitive performance? Does the effect depend on competition environment? We hypothesized that with increasing conspecific abundance and decreasing heterospecific abundance, (1) M. micrantha increased intraspecific competitive ability but decreased interspecific competitive ability; (2) the effect of soil biota was competition environment‐dependent; specifically, interspecific competitive ability was increasingly more suppressed by the presence of soil biota relative to intraspecific competitive ability  was recorded when it was transplanted after three weeks of growth. Each pot was filled with 550 ml of sterilized potting soil, inoculated with 70 ml of field‐collecting live soil or an autoclaved sample of the same soil, and topped with 80 ml of sterilized potting soil. In both live and sterilized soil, M. micrantha plants were grown either alone or with intra‐ or interspecific competitors. To simulate intraspecific competition, each M. micrantha plant from the seven focal populations was grown with two competing M. micrantha plants from the additional site. To simulate interspecific competition, each M. micrantha plant was grown with a B. pilosa and a P. chinensis plant. Each competition × soil treatment combination was repeated for the three aforementioned soil sources. Such was done to minimize potential soil sample bias as soil biota can vary from site to site  of both focal and neighbor plants were harvested. The biomass was dried at 60°C for 72 h and weighed. Fourteen plants died during the experiment and their pots were removed.Seeds of M. micrantha is highly invasive, we harvested all plants before M. micrantha flowered to eliminate unintentional spread.Plant biomass was used as the proxy of competitive ability. Fecundity‐related traits such as seed production and flowering phenology, which were often used to measure competitive ability  was used to estimate intra‐ vs. interspecific competitive ability. RCA was calculated for each focal population in live and sterilized soils as follows:M. micrantha relative competitive ability was the response variable, M. micrantha percent cover, soil treatment and their two‐way interactions, and soil source as the fixed factors; initial size of focal M. micrantha plants in intra‐ and interspecific competition and soil PC1 as the covariates; and population and block as the random factors.A value of 1 indicates equivalent intra‐ vs. interspecific competitive ability. A linear model was run with M. micrantha percent cover to fully test the effect of the competition environment on competitive ability. Last, because correlated environmental factors may confound the interpretation of the results, to explore this possibility, the aforementioned models were rerun with longitude, latitude, and altitude of M. micrantha population as the additional covariates. All analyses were performed in JMP 16 Pro .The aforementioned models were rerun but substituted the heterospecific plants percent cover in place of the 33.1Mikania micrantha populations from high conspecific abundance sites tended to produce higher biomass in intraspecific competition but lower biomass in interspecific competition environments, compared with those populations from low conspecific abundance sites in live soil  M. micrantha increased intraspecific competition tolerance and intra‐ vs. interspecific competitive ability but decreased interspecific competition tolerance; (2) M. micrantha increased tolerance of the negative soil biota effect, evidenced by the growth being less inhibited by the presence of soil biota when growing in isolation; (3) interspecific competition tolerance was increasingly suppressed by the presence of soil biota, but intraspecific competition tolerance was less evidently affected. Together, our results strongly suggest that soil biota mediate the evolutionary shifts in intra‐ and interspecific competitive ability of M. micrantha during range expansion in South China.In the present study, we investigated the interactive effects of the competition environment and soil biota on Mikania micrantha increased intra‐ vs. interspecific competitive ability and intraspecific competition tolerance in response to the shifting competition environment from heterospecific to conspecific dominant, suggesting M. micrantha has a great potential for rapid adaptation to local competition environment. This result emphasizes the importance of maintaining intraspecific competitive ability on population persistence during invasion course. In fact, intraspecific competition tolerance is a promising competitive strategy for invasive plants, especially in the late invasion phase  with increasing conspecific abundance . Evidence was also found in previous studies that reduction in AMF associations promotes competitive tolerance in invasive species ; Formal analysis (lead); Funding acquisition ; Investigation (lead); Writing‐original draft (lead); Writing‐review & editing (lead). Qiaoqiao Huang: Conceptualization ; Formal analysis (supporting); Funding acquisition ; Writing‐review & editing (supporting). Xianhua Gan: Investigation (supporting); Writing‐review & editing (supporting). Weiqiang Zhang: Investigation (supporting); Writing‐review & editing (supporting). Yuedong Guo: Investigation (supporting); Writing‐review & editing (supporting). Yuhui Huang: Investigation (supporting); Writing‐review & editing (supporting).Appendix S1Click here for additional data file.