Tri-state logic computation by activating DNA origami chains.

The invention of DNA nanotechnology has enabled molecular computation as a promising substitute for traditional semiconductors which are limited to two-dimensional architectures and by heating problems resulting from densification. Current studies of logic gates achieved using DNA molecules are predominately focused on two-state operations (AND, OR, etc.); however, realizing tri-state logic (high impedance Z) in DNA computation is understudied. Here we actively fold DNA origami chain-like hinged rods to induce conformational changes that return tri-state logic signals. We use rigid six helix-bundle (6HB) DNA origami to self-assemble a linear trimer chain as a circuit platform with functional single-stranded (ss) DNA near each semi-flexible hinge. The presence or absence of ssDNA enable and input strands allows hybridization to take place at the hinges, activating one fold (0) or two folds (1) from the straight linear geometry (defined as High-Z) of the trimer chain. We design two different tri-state logic gate platforms, buffer and inverter, with corresponding enable/input ssDNA to unambiguously return tri-state signals, characterized by Atomic Force Microscopy (AFM) and/or agarose gel electrophoresis (GEL). Our work on tri-state logic significantly enhances DNA computation beyond the current two-state Boolean logic with both research and industrial applications, including cellular treatments and living matter utilizing the biocompatibility of DNA molecules.

Non-equilibrium structural and dynamic behaviors of active polymers in complex and crowded environments.

Active matter systems, which convert internal chemical energy or energy from the environment into directed motion, are ubiquitous in nature and exhibit a range of emerging non-equilibrium behaviors. However, most of the current works on active matter have been devoted to particles, and the study of active polymers has only recently come into the spotlight due to their prevalence within living organisms. The intricate interplay between activity and conformational degrees of freedom gives rise to novel structural and dynamical behaviors of active polymers. Research in active polymers remarkably broadens diverse concepts of polymer physics, such as molecular architecture, dynamics, scaling and so on, which is of significant importance for the development of new polymer materials with unique performance. Furthermore, active polymers are often found in strongly interacting and crowded systems and in complex environments, so that the understanding of this behavior is essential for future developments of novel polymer-based biomaterials. This review thereby focuses on the study of active polymers in complex and crowded environments, and aims to provide insights into the fundamental physics underlying the adaptive and collective behaviors far from equilibrium, as well as the open challenges that the field is currently facing.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Effects of stable and fluctuating soil water on the agronomic and biological performance of root vegetables.

Compared to fluctuating soil water (FW) conditions, stable soil water (SW) can increase plant water use efficiency (WUE) and improve crop growth and aboveground yield. It is unknown, however, how stable and fluctuating soil water affect root vegetables. Here, the effects of SW and FW were studied on cherry radish in a pot experiment, using negative pressure irrigation and conventional irrigation, respectively. The assessed effects included agronomic parameters, physiological indices, yield, quality and WUE of cherry radish. Results showed that under similarly average soil water contents, compared with FW, SW increased plant photosynthetic rate, stomatal conductance and transpiration rate, decreased leaf proline content by 13.7-73.3% and malondialdehyde content by 12.5-40.0%, and increased soluble sugars content by 6.3-22.1%. Cherry radish had greater biomass accumulation and nutrient uptake in SW than in FW. Indeed, SW increased radish output by 34.6-94.1% with no influence on root/shoot ratio or root quality. In conclusion, soil water stability affected directly the water physiological indicators of cherry radish and indirectly its agronomic attributes and nutrient uptake, which in turn influenced the crop biomass and yield, as well as WUE. This study provides a new perspective for improving agronomy of root crops and WUE through managing soil water stability.

Programmable Potentials Choreograph Defects in a Colloidal Crystal Shell.

Crystallization on spherical surfaces is obliged by topology to induce lattice defects. But controlling the organization of such defects remains a great challenge due to the long-range constraints of the curved geometry. Here, we report on DNA-coated colloids whose programmable interaction potentials can be used to regulate the arrangement of defects and even achieve perfect icosahedral order on a sphere. Combined simulations and theoretical analysis show how the potential can be tuned by changing the temperature, thereby controlling the number of defects. An explicit expression for the effective potential is derived, allowing us to distinguish the effects of entropic repulsion and enthalpic attraction. Altogether, the present findings provide insights into the physics of crystallization on curved spaces and may be used for designing desired crystal geometries.

Toward three-dimensional DNA industrial nanorobots.

Nanoscale industrial robots have potential as manufacturing platforms and are capable of automatically performing repetitive tasks to handle and produce nanomaterials with consistent precision and accuracy. We demonstrate a DNA industrial nanorobot that fabricates a three-dimensional (3D), optically active chiral structure from optically inactive parts. By making use of externally controlled temperature and ultraviolet (UV) light, our programmable robot, ~100 nanometers in size, grabs different parts, positions and aligns them so that they can be welded, releases the construct, and returns to its original configuration ready for its next operation. Our robot can also self-replicate its 3D structure and functions, surpassing single-step templating (restricted to two dimensions) by using folding to access the third dimension and more degrees of freedom. Our introduction of multiple-axis precise folding and positioning as a tool/technology for nanomanufacturing will open the door to more complex and useful nano- and microdevices.

Atherosclerosis indexes and incident T2DM in middle-aged and older adults: evidence from a cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an expanding global health problem, requiring effective methods for predicting and diagnosing in its early stages of development. Previous studies reported the prognostic value of the atherosclerosis indexes in both cardiovascular diseases and T2DM. However, the predictive performance of Non-HDL-C, AI, AIP, TG/HDL-C and LCI indexes on the risk of T2DM remains unclear. This study aims to compare the five atherosclerosis indexes for predicting T2DM in middle-aged and elderly Chinese. METHODS: Data are collected from wave 2011 and wave 2015 of China Health and Retirement Longitudinal Study (CHARLS). Multi-variate logistic regression models were used to estimate odds ratio (OR) with 95% confidence interval (CI) of incident T2DM with five atherosclerosis indexes, and the restricted cubic splines were used to visualize the dose-response relationships. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to compare the performance of the five atherosclerosis indexes in predicting T2DM. RESULTS: A total of 504 (10.97%) participants had T2DM. Multi-variate logistic regression analysis showed that five atherosclerosis indexes were associated with T2DM, with adjusted ORs (95% CIs) of 1.29 (1.15-1.45), 1.29 (1.18-1.42), 1.45 (1.29-1.62), 1.41 (1.25-1.59) and 1.34 (1.23-1.48) for each IQR increment in Non-HDL-C, TG/HDLC, AI, AIP and LCI, respectively. Restricted cubic spline regression showed a nonlinear correlation between five atherosclerosis indexes and the risk of T2DM (p for nonlinear < 0.001). According to the ROC curve analysis, LCI had the highest AUC (0.587 [0.574-0.600]). CONCLUSION: We found that LCI, compared with other indexes, was a better predictor in the clinical setting for identifying individuals with T2DM in middle-aged and elderly Chinese. LCI monitoring might help in the early identification of individuals at high risk of T2DM.

Stable Soil Moisture Improves the Water Use Efficiency of Maize by Alleviating Short-Term Soil Water Stress.

Weaker temporal variation of soil moisture can improve crop water use efficiency (WUE), but its physiological mechanism was still unclear. To explore the mechanism, an organized experiment was conducted in Beijing from June to September. From the jointing stage to maturity stage of maize, stable soil moisture (SSM) and fluctuating soil moisture (FSM) were established with Pressure Potential Difference-Crop Initiate Drawing Water (PCI) and manual irrigation (MI), respectively, to explore the physiological mechanism of SSM to improve maize WUE. Among them, PCI treatments were set with 3 pressure differences of -5, -10, and -15 kPa, and MI treatment was watering every 3 days with the irrigation amount of 9.3 mm. The results showed that (1) after water treatment, the average soil water content of PCI-5 kPa, PCI-10 kPa, PCI-15 kPa, and MI treatments were 53% field capacity (FC), 47, 38, and 78% FC, respectively. It was SSM with weak temporal variation under PCI treatments, and FSM with medium temporal variation under MI treatment. (2) PCI treatments reduced the content of proline, malondialdehyde, and abscisic acid in each organ of maize. (3) Compared with FSM 78% FC, the maize root activity at the filling stage of 53% FC SSM and 47% FC SSM increased significantly by 57.1 and 28.6%, respectively, and the carbon isotope discrimination value (Δ13C) in bracts of the two treatments increased by 18.3 and 10.4%, respectively. (4) There was a very significant positive correlation between WUE based on biomass (WUEb) and Δ13C in bracts. In conclusion, a large temporal variation of soil moisture was an important factor that caused water stress in maize. Under SSM treatments, the accumulation of abscisic acid, proline, and malondialdehyde was synergistically reduced. SSM improved the WUE of maize by alleviating short-term soil water stress caused by the fluctuation of soil moisture.

Report on the 19th international symposium on geo-disaster reduction/high-level academic forum on disaster mitigation and integrated risk defense on the Plateau, 12-15 July 2021, Xining, China.

The joint event of 19th International Symposium on Geo-disaster Reduction (19ISGdR) and High-Level Academic Forum on Disaster Mitigation and Integrated Risk Defense on the Plateau was held on 11-15 July in Xining, Qinghai Province, China, focusing on the theme of "Geological disaster and integrated risk defense". This event consisted of keynote lectures, invited lectures, and Youth forum, which provided a platform for scientists, industrial professionals and young scholars to share their research progress and exchange novel ideas on geo-disaster reduction in a hybrid way of offline and online. A post-symposium field trip for three days was also conducted in the joint area between Qinghai-Tibet plateau and Loess plateau.

Divalent Multilinking Bonds Control Growth and Morphology of Nanopolymers.

Assembly of nanoscale objects into linear architectures resembling molecular polymers is a basic organization resulting from divalent interactions. Such linear architectures occur for particles with two binding patches on opposite sides, known as Janus particles. However, unlike molecular systems where valence bonds can be envisioned as pointlike interactions nanoscale patches are often realized through multiple molecular linkages. The relationship between the characteristics of these linkages, the resulting interpatch connectivity, and assembly morphology is not well-explored. Here, we investigate assembly behavior of model divalent nanomonomers, DNA nanocuboid with tailorable multilinking bonds. Our study reveals that the characteristics of individual molecular linkages and their collective properties have a profound effect on nanomonomer reactivity and resulting morphologies. Beyond linear nanopolymers, a common signature of divalent nanomonomers, we observe an effective valence increase as linkages lengthened, leading to the nanopolymer bundling. The experimental findings are rationalized by molecular dynamics simulations.

Entropy-Driven Unconventional Crystallization of Spherical Colloidal Nanocrystals Confined in Wide Cylinders.

The densest packings of identical spherical colloidal nanocrystals in a thin cylinder generally give rise to confinement-induced chiral ordering. Here, we demonstrate that entropy can invalidate Pauling's packing rules for the nanocrystals confined in wide cylinders and novel ordered phases, where chiral ordering is broken, emerge. The nucleation and growth of spherical colloidal nanocrystals in the wide cylinders exhibit unique mechanisms which are distinctly different from that of thin ones. Furthermore, theoretical models which capture the essential physics of the ordering transitions are developed to reproduce the achiral ordering and reveal that the ordered phases are thermodynamically stable and stabilized through confinement-mediated entropic effect. These findings demonstrate that entropy arising from thermal motion can invalidate Pauling's packing rules of spherical colloidal nanocrystals confined in cylinders, which provides new insights into confinement physics of colloidal particles and might inspire nonintuitive design rules for the fabrication of novel ordered phases through confinement.

Microchemomechanical devices using DNA hybridization.

The programmability of DNA oligonucleotides has led to sophisticated DNA nanotechnology and considerable research on DNA nanomachines powered by DNA hybridization. Here, we investigate an extension of this technology to the micrometer-colloidal scale, in which observations and measurements can be made in real time/space using optical microscopy and holographic optical tweezers. We use semirigid DNA origami structures, hinges with mechanical advantage, self-assembled into a nine-hinge, accordion-like chemomechanical device, with one end anchored to a substrate and a colloidal bead attached to the other end. Pulling the bead converts the mechanical energy into chemical energy stored by unzipping the DNA that bridges the hinge. Releasing the bead returns this energy in rapid (>20 µm/s) motion of the bead. Force-extension curves yield energy storage/retrieval in these devices that is very high. We also demonstrate remote activation and sensing-pulling the bead enables binding at a distant site. This work opens the door to easily designed and constructed micromechanical devices that bridge the molecular and colloidal/cellular scales.

Entropy at Bio-Nano Interfaces.

Entropy, one of the central concepts of thermodynamics, can be a predominant contribution to structural formation and transition. Although it is well-known that diverse forces and energies can significantly contribute to the structures and activities at bio-nano interfaces, the potential entropic contribution remains less well understood. Therefore, this review article seeks to provide a conceptual framework demonstrating that entropy can be exploited to shape the physicochemical properties of bio-nano interfaces and thereby regulate the structures, responses, and functions of biological systems. We introduce the typical types of entropy that matter at bio-nano interfaces. Moreover, some key characteristics featuring entropy at bio-nano interfaces, such as the difference between entropic force and energetic interaction and the associated implications for biomimetic research, are discussed. We expect that this review could stimulate further effort in the fundamental research of entropy in biology and in the biological applications of entropic effects in designer biomaterials.

Cellular Uptake of Active Particles.

Active particles are widely recognized to potentially revolutionize technologies in numerous biomedical applications. However, the physical origin behind cellular uptake of these particles in the nonequilibrium state remains scarcely understood. Here we combine Brownian dynamics simulation as well as theoretical analysis to provide the criterion for cellular uptake of active particles, related to various physical attributes. Upon enhancing the activity, the uptake efficiency for the active particles with tilted orientation is examined to be nonmonotonic, in stark contrast to the monotonic dependence for active particles orientated normally to the membrane. This can be attributed to the interplay between membrane adhesion energy and kinetic energy of active particles, resulting in unique kinetic pathways. Furthermore, a theoretical model that captures the essential physics of the cellular endocytosis process is developed to reproduce this nonmonotonic feature. The results are of immediate interest to understand and tune activity-mediated cellular interaction and internalization of such emerging colloids.

Entropy-Mediated Mechanomutable Microstructures and Mechanoresponsive Thermal Transport of Nanoparticle Self-Assembly in Block Copolymers.

Despite decades of intense research efforts on the self-assembly of nanoparticles in mesophase-forming copolymers, the progress in practical applications is impeded by the lack of knowledge about the dynamic transition of such hierarchical nanostructures in an environment bearing an external load. Here, we show that the hierarchical self-assembly of nanoparticles in block copolymer scaffolds can be made to significantly alternate by external compression, characterized by a continuous and reverse transition among various distribution states of nanoparticles in their preferential domains. Theoretical analysis reveals that compression-induced transition of the nanoparticle distribution can be fundamentally attributed to unique entropic effects originating from the compacted block chains. Further, we demonstrate that the hierarchical nanostructures with different distribution states of nanoparticles can lead to mechanomutable phonon transport properties. The findings reveal the mechanoresponsive behaviors of the hierarchical nanostructures of block copolymer-based nanocomposites and their potential applications as thermal interface materials with tailored thermal conductivity.

Optimal ligand-receptor binding for highly efficient capture of vesicles in nanofluidic transportation.

Optimizing ligand-receptor binding is essential for exploiting advanced biomedical applications from targeting drug delivery to biosensing. A key challenge is how optimized ligand-receptor binding can be realized during the transport of ligand-modified soft materials through a nanofluidic channel. Here, by combining computer simulations and theoretical analysis, we report that the ligand-receptor binding and resulting capture probability of ligand-functionalized vesicles nonmonotonically depend on their some intrinsic properties, e.g., chain stiffness and vesicle rigidity, during their transport through a nanochannel with imposed Poiseuille flow. Particularly, we find that the systems with semiflexible ligand and receptor chains possess the optimal ligand-receptor binding and capture probability. An analytical model of the blob theory is developed to capture the simulation results quantitatively, leading to a mechanistic interpretation of the optimal vesicle capture based on the conformational-entropy effect. Examination of the detailed dynamics reveals the active rearrangement of ligand-receptor binding during the transport process. Furthermore, the hairy vesicle with moderate rigidity is found to display an enhanced capture probability superior to that of both its soft and hard counterparts, which is rationalized by the faster and more periodic tumbling motion of the semi-rigid vesicle. Our findings highlight that precise control of the intrinsic properties of ligands and receptors as well as the vesicle rigidity can be a versatile strategy in optimizing the ligand-receptor binding in nanofluidic transportation towards advantageous biomedical applications.

Plastic Crystal-to-Crystal Transition of Janus Particles under Shear.

Colloidal Janus spheres in the bulk typically spontaneously assemble into plastic crystalline phases, while particle orientations exhibit glasslike dynamics without long-range order. Through Brownian dynamics simulations, we demonstrate that shear can trigger a phase transition from an isotropic crystal with orientational disorder to an orientationally ordered crystal with lamellae along the shear direction. This nonequilibrium transition is accompanied with the orientational ordering following a nucleation and growth mechanism. By performing a phenomenological extension of free energy analysis, we reveal that the nucleation originates from the orientation fluctuations induced by shear. The growth of the orientationally crystalline cluster is examined to be disklike, captured by developing a lattice model with memoryless state functions. These findings bring new insights into the mechanisms for the ordering transition of anisotropic particles at nonequilibrium states.

Entropic Effects in Polymer Nanocomposites.

Polymer nanocomposite materials, consisting of a polymer matrix embedded with nanoscale fillers or additives that reinforce the inherent properties of the matrix polymer, play a key role in many industrial applications. Understanding of the relation between thermodynamic interactions and macroscopic morphologies of the composites allow for the optimization of design and mechanical processing. This review article summarizes the recent advancement in various aspects of entropic effects in polymer nanocomposites, and highlights molecular methods used to perform numerical simulations, morphologies and phase behaviors of polymer matrices and fillers, and characteristic parameters that significantly correlate with entropic interactions in polymer nanocomposites. Experimental findings and insight obtained from theories and simulations are combined to understand how the entropic effects are turned into effective interparticle interactions that can be harnessed for tailoring nanostructures of polymer nanocomposites.

Hierarchical Crystals Formed from DNA-Functionalized Janus Nanoparticles.

Harnessing anisotropic interactions in a DNA-mediated nanoparticle assembly holds great promise as a rational strategy to advance this important area. Here, using molecular dynamics simulations, we report the formation of novel hierarchical crystalline assemblies of Janus nanoparticles functionalized with two types of DNA chains (DNA-JNPs). We find that in addition to the primary nanoparticle crystallization into face-centered cubic (FCC) structure, sequence-specific DNA hybridization events further direct the rotational orientation of the DNA-JNPs to diverse secondary crystalline phases including simple cubic (SC), tetragonally ordered cylinder (P4), and lamella (L) structures, which are mapped in the phase diagrams relating to various asymmetric parameters. The crystallization dynamics of such hierarchical crystals is featured by two consequent processes: entropy-dominated translational order for the primary crystalline structure and enthalpy-dominated rotational order for the secondary crystalline structure. For DNA-JNPs with high asymmetry in DNA sequence length, tetrahedral nanoclusters tend to be favored, which is revealed to be governed by the conformational entropy penalty caused by bounded DNA chains. This work might bear important consequences for constructing new classes of nanoparticle crystals with designed structures and properties at multiple levels and in a predictable manner.

How Implementation of Entropy in Driving Structural Ordering of Nanoparticles Relates to Assembly Kinetics: Insight into Reaction-Induced Interfacial Assembly of Janus Nanoparticles.

The ability to understand and exploit entropic contributions to ordering transition is of essential importance in the design of self-assembling systems with well-controlled structures. However, much less is known about the role of assembly kinetics in entropy-driven phase behaviors. Here, by combining computer simulations and theoretical analysis, we report that the implementation of entropy in driving phase transition significantly depends on the kinetic process in the reaction-induced self-assembly of newly designed nanoparticle systems. In particular, such systems comprise binary Janus nanoparticles at the fluid-fluid interface and undergo phase transition driven by entropy and controlled by the polymerization reaction initiated from the surfaces of just one component of nanoparticles. Our simulations demonstrate that the competition between the reaction rate and the diffusive dynamics of nanoparticles governs the implementation of entropy in driving the phase transition from randomly mixed phase to intercalated phase in these interfacial nanoparticle mixtures, which thereby results in diverse kinetic pathways. At low reaction rates, the transition exhibits abrupt jump in the mixing parameter, in a similar way to first-order, equilibrium phase transition. Increasing the reaction rate diminishes the jumps until the transitions become continuous, behaving as a second-order-like phase transition, where a critical exponent, characterizing the transition, can be identified. We finally develop an analytical model of the blob theory of polymer chains to complement the simulation results and reveal essential scaling laws of the entropy-driven phase behaviors. In effect, our results allow for further opportunities to amplify the entropic contributions to the materials design via kinetic control.