Association between stress hyperglycemia ratio and functional outcomes in patients with acute ischemic stroke.

OBJECTIVE: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and poor functional outcomes at 90 days in patients with acute ischemic stroke (AIS). METHODS: This study retrospectively collected 1988 AIS patients admitted to two hospitals in the Shenzhen area between January 2022 and March 2023. A total of 1255 patients with Fasting Blood-glucose (FBG) and hemoglobin A1c (HbA1C) values at admission were included in this analysis. SHR, measured by FBG/HbA1C, was evaluated as both a tri-categorical variable (Tertile 1: ≤ 0.83; Tertile 2: 0.84 -0.95; Tertile 3: ≥ 0.96). The outcome was poor functional outcomes (modified Rankin Scale [mRS] score 2-6) at 90 days. We performed univariate analysis, multiple equation regression analysis, stratified analysis, and interactive analysis. RESULTS: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving poor functional outcomes (adjusted odds ratio, OR = 2.84, 95% CI: 2.02-3.99, P < 0.0001) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for white blood cell count, neutrophil count, lymphocyte count, fasting blood glucose, stroke type, intravenous thrombolytic therapy, baseline Glasgow score, and baseline NIHSS score. CONCLUSION: SHR, as measured by the FBG/HbA1C, was associated with an increased odds of achieving poor functional outcomes in patients with AIS at 90 days.

The nonlinear relationship between triglyceride glucose-waist circumference and stroke risk in middle-aged and elderly people: a nationwide prospective cohort study of the CHARLS.

BACKGROUND AND AIMS: Numerous research have focused on the relationship of metabolic markers and stroke risk, yet limited research has focused on the triglyceride glucose-waist circumference (TyG-WC) index. This study explored the possible association of TyG-WC and stroke among moderately aged and old Chinese adults over 45 years of age. METHODS: This observational cohort analysis involved 9054 participants from the Chinese Longitudinal Study of Health and Retirement and employed a standardized questionnaire administered via in-person interviews. Cox proportional hazard model, smoothed curve fitting, and threshold effect analysis were conducted for examining the potential nonlinear relationships among TyG-WC and stroke risk. RESULTS: Within an average follow-up period of six years, 463 new strokes occurred, representing 5.11% of the total number of patients. After adjusting for possible confounding factors, a nonlinear association between TyG-WC and stroke risk was identified, with a significant dose-response relationship (P = 0.023 for the log-likelihood ratio test). A turning point was identified at the TyG-WC level of 554.48, beyond that the likelihood of stroke increased markedly (HR = 1.323, 95% CI = 1.098-1.594, P = 0.003). CONCLUSION: This study revealed a specific curvilinear association with the TyG-WC score and stroke risk, identifying a key threshold value. This study focused on Chinese middle-aged and senior adults over the age of 45, emphasizing that increased stroke risk is linked to higher TyG-WC levels.

Catalytic assembly of symmetric diblock copolymers in a thin film: a dissipative particle dynamics simulation study.

Obtaining a thin block copolymer film with a perfect structure by self-assembly is difficult because the system is, in general, trapped in a metastable state. We used dissipative particle dynamics (DPD) to investigate the self-assembly of AB symmetric diblock copolymers in a thin film. We discovered that addition of a small molecule (molecule C) as the third composition could help the system evade the metastable state. Therefore, imperfect structures could be corrected, and ordered structures formed. Analogous to the performance of a catalyst in catalytic chemistry, molecule C could promote assembly into an ordered structure, but was less involved within the polymer phase. Moreover, simulation results showed that the content of molecule C and its repulsive interactions with blocks A and B were quite important for promoting assembly into ordered structures effectively.

Programming colloidal bonding using DNA strand-displacement circuitry.

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.

Oxygen-Tolerant Photoredox Catalysis Triggers Nitric Oxide Release for Antibacterial Applications.

Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV-absorbing N,N'-dinitroso-1,4-phenylenediamine derivatives can be selectively activated by fac-Ir(ppy)3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac-Ir(ppy)3 , thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen-tolerant photoredox catalysis-mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo.

Red-Light-Mediated Photoredox Catalysis Enables Self-Reporting Nitric Oxide Release for Efficient Antibacterial Treatment.

Nitric oxide (NO) serves as a key regulator of many physiological processes and as a potent therapeutic agent. The local delivery of NO is important to achieve target therapeutic outcomes due to the toxicity of NO at high concentrations. Although light stimulus represents a non-invasive tool with spatiotemporal precision to mediate NO release, many photoresponsive NO-releasing molecules can only respond to ultraviolet (UV) or near-UV visible light with low penetration and high phototoxicity. We report that coumarin-based NO donors with maximal absorbances at 328 nm can be activated under (deep) red-light (630 or 700 nm) irradiation in the presence of palladium(II) tetraphenyltetrabenzoporphyrin, enabling stoichiometric and self-reporting NO release with a photolysis quantum yield of 8 % via photoredox catalysis. This NO-releasing platform with ciprofloxacin loading can eradicate Pseudomonas aeruginosa biofilm in vitro and treat cutaneous abscesses in vivo.

A Scalable "Junction Substrate" to Engineer Robust DNA Circuits.

Versatile building blocks are essential for building complex and scaled-up DNA circuits. In this study, we propose a conceptually new scalable architecture called a "junction substrate" (J-substrate) that is linked by prepurified double-stranded DNA molecules. As a proof-of-concept, this novel type of substrate has been utilized to build multi-input DNA circuits, offering several advantages over the conventional substrate (referred to as a "linear substrate", L-substrate). First, the J-substrate does not require long DNA strands, thus avoiding significant synthetic errors and costs. Second, the traditional PAGE purification method is technically facilitated to obtain high-purity substrates, whereby the initial leakage is effectively eliminated. Third, the asymptotic leakage is eliminated by introducing the "junction". Finally, circuits with the optimized J-substrate architecture exhibit fast kinetics. We believe that the proposed architecture constitutes a sophisticated chassis for constructing complex circuits.

Optimizing the Toehold Strategy of On-Chip Nucleic Acid Hybridization Probe for the Discrimination of Single Nucleotide Polymorphism.

The synthetic DNA hybridization probe has proved its importance in biology and biotechnology. In this study, taking advantage of a novel analytical technique called dual polarization interferometry (DPI), the influence of the toehold strategy of on-chip DNA hybridization probe on the discrimination of single nucleotide polymorphism (SNP) was investigated. Through adjusting the toehold length, the toehold strategies of on-chip toehold exchange probe were thoroughly optimized. For the "6/5" probe, an optimal discrimination factor of 78% against the spurious target was achieved. Moreover, the ability of the on-chip probe in SNP discrimination was significantly enhanced compared to its pure solution counterpart. This simple and rapid detection method for SNP discrimination based on the on-chip toehold exchange probe will show great potential in disease diagnosis.

Theoretical Insights into the Interactions between Star-Shaped Antimicrobial Polypeptides and Bacterial Membranes.

A structurally nanoengineered antimicrobial polypeptide consisting of lysine and valine residues is a new class of antimicrobial agent with superior antibacterial activity against multidrug-resistant bacteria and low toxicity toward mammalian cells. Utilizing coarse-grained models, we studied the interactions of microbial cytoplasmic membranes with polypeptides of either (K2V1)5 (star-KV) or CM15 (star-CM15). Our computational results verify the low toxicity of polypeptides of (K2V1)5 toward the dipalmitoyl phosphatidylcholine bilayer. This low toxicity is demonstrated to originate from weakened hydrophobicity combined with its random coil conformation for (K2V1)5 because of the highly abundant valine residues, compared with the typical antimicrobial peptides, such as CM15. In the interactions with a palmitoyl-oleoyl-phosphatidylethanolamine/palmitoyl-oleoyl-phosphatidylglycerol bilayer, star-KV has greater ability in phase separation and generation of phase boundary defects not only in lipid redistribution but also in lateral dynamic movements, although both star-KV and star-CM15 can extract the phosphatidylglycerol lipids and purify the phosphatidylethanolamine lipids into continuum domains. We suggest that the polypeptide of (K2V1)5 can nondisruptively kill bacteria by hampering bacterial metabolism through reorganizing lipid domain distribution and simultaneously "freezing" lipid movement.

Shape-dependent internalization kinetics of nanoparticles by membranes.

Internalization of nanoparticles by biomembranes is critical for nanomedicine development; however, this process, especially its dynamics aspect, is still not well understood. Using coarse-grained molecular modeling combined with free energy calculations, we studied the endocytic process for spherical, prolate and oblate particles with varied aspect ratios, volumes and interaction strengths. Rich dynamic wrapping behaviors have been observed. Small ellipsoids follow a pathway that includes particle laying-down, membrane invagination and wrapping, and then disruption of the membrane neck. However, the step of particle laying-down is skipped for large ellipsoids. Because of the significantly decreased local mean curvature at the side edge (oblate ellipsoid) or tips (prolate ellipsoid), the rotation is less favorable for particles with larger volume. Given the existence of a local minimum and an energy barrier during the endocytic process presented by our free energy calculations, the oblate particle provides longer endocytic time than the corresponding prolate particle. For large particles, the free energy surfaces are smooth, with no local minimum. When we increase the interaction strength between the membrane and the particle, the endocytic process is greatly affected. Moreover, a "sandwiched structure", in which the particle lays between the two membrane layers, was observed for both prolate and oblate particles.

Integrating DNA-strand-displacement circuitry with self-assembly of spherical nucleic acids.

Programmable and algorithmic behaviors of DNA molecules allow one to control the structures of DNA-assembled materials with nanometer precision and to construct complex networks with digital and analog behaviors. Here we developed a way of integrating a DNA-strand-displacement circuit with self-assembly of spherical nucleic acids, wherein a single DNA strand was used to initiate and catalyze the operation of upstream circuits to release a single strand that subsequently triggers self-assembly of spherical nucleic acids in downstream circuits, realizing a programmable kinetic control of self-assembly of spherical nucleic acids. Through utilizing this method, single-nucleotide polymorphisms or indels occurring at different positions of a sequence of oligonucleotide were unambiguously discriminated. We provide here a sophisticated way of combining the DNA-strand-displacement-based characteristic of DNA with the distinct assembly properties of inorganic nanoparticles, which may find broad potential applications in the fabrication of a wide range of complex multicomponent devices and architectures.

DNA Polymer Brush Patterning through Photocontrollable Surface-Initiated DNA Hybridization Chain Reaction.

The fabrication of DNA polymer brushes with spatial resolution onto a solid surface is a crucial step for biochip research and related applications, cell-free gene expression study, and even artificial cell fabrication. Here, for the first time, a DNA polymer brush patterning method is reported based on the photoactivation of an ortho-nitrobenzyl linker-embedded DNA hairpin structure and a subsequent surface-initiated DNA hybridization chain reaction (HCR). Inert DNA hairpins are exposed to ultraviolet light irradiation to generate DNA duplexes with two active sticky ends (toeholds) in a programmable manner. These activated DNA duplexes can initiate DNA HCR to generate multifunctional patterned DNA polymer brushes with complex geometrical shapes. Different multifunctional DNA polymer brush patterns can be fabricated on certain areas of the same solid surface using this method. Moreover, the patterned DNA brush surface can be used to capture target molecules in a desired manner.

What Controls the "Off/On Switch" in the Toehold-Mediated Strand Displacement Reaction on DNA Conjugated Gold Nanoparticles?

In DNA dynamic nanotechnology, a toehold-mediated DNA strand-displacement reaction has demonstrated its capability in building complex autonomous system. In most cases, the reaction is performed in pure DNA solution that is essentially a one-phase system. In the present work, we systematically investigated the reaction in a heterogeneous media, in which the strand that implements a displacing action is conjugated on gold nanoparticles. By monitoring the kinetics of spherical nucleic acid (SNA) assembly driven by toehold-mediated strand displacement reaction, we observed significant differences, i.e., the abrupt jump in behavior of an "off/on switch", in the reaction rate when the invading toehold was extended to eight bases from seven bases. These phenomena are attributed to the effect of steric hindrance arising from the high density of invading strand conjugated to AuNPs. Based on these studies, an INHIBIT logic gate presenting good selectivity was developed.

The combination of gold nanorods and nanoparticles with DNA nanodevices for logic gates construction.

In this work, two DNA nanodevices were constructed utilizing a DNA strand displacement reaction. With the assistance of gold nanoparticles (AuNPs) and gold nanorods (AuNRs), the autonomous reactions can be reflected from the aggregation states of nanoparticles. By sequence design and the two non-overlapping double hump-like UV-vis spectral peaks of AuNPs and AuNRs, two logic gates with multiple inputs and outputs were successfully run with expected outcomes. This method not only shows how to achieve computing with multiple logic calculations but also has great potential for multiple targets detection.

DNA conformational flexibility study using phosphate backbone neutralization model.

Due to the critical role of DNA in the processes of the cell cycle, the structural and physicochemical properties of DNA have long been of concern. In the present work, the effect of interplay between the DNA duplex and metal ions in solution on the DNA structure and conformational flexibility is studied by comparing the structure and dynamic conformational behavior of a duplex in a normal form and its "null isomer" using molecular dynamics methods. It was found that the phosphate neutralization changes the cation atmosphere around the DNA duplex greatly, increases the major groove width, decreases the minor groove width, and reduces the global bending direction preference. We also noted that the probability of BI phosphate linkages increases significantly because of the charge reduction in the backbone phosphate groups. More importantly, we found that the electrostatic effect on the DNA conformational flexibility is dependent on the sequence; that is, the phosphate backbone neutralization induces the global dynamic bending to be less flexible for GC-rich sequences but more flexible for AT-rich sequences.

Enhancing the efficiency of lithium intercalation in carbon nanotube bundles using surface functional groups.

The effect of surface functionalization on the ability and kinetics of lithium intercalation in carbon nanotube (CNT) bundles has been studied by comparing the dynamical behaviors of lithium (Li) ions in pristine and -NH2 functionalized CNTs via ab initio molecular dynamics simulations. It was observed that lithium intercalation has been achieved quickly for both the pristine and surface functionalized CNT bundle. Our calculations demonstrated for the first time that CNT functionalization improved the efficiency of lithium intercalation significantly at both low and high Li ion density. Moreover, we found that keeping the nanotubes apart with an appropriate distance and charging the battery at a rational rate were beneficial to achieve a high rate of lithium intercalation. Besides, the calculated adsorption energy curves indicated that the potential wells in the system of -NH2 functionalized CNT were deeper than that of the pristine CNT bundle by 0.74 eV, and a third energy minimum with a value of 2.64 eV existed at the midpoint of the central axis of the nanotube. Thus, it would be more difficult to remove Li ions from the nanotube interior after surface functionalization. The barrier for lithium diffusion in the interior of the nanotube is greatly decreased because of the surface functional groups. Based on these results, we would suggest to "damage" the nanotube by introducing defects at its sidewall in order to improve not only the capacity of surface functionalized CNTs but also the efficiency of lithium intercalation and deintercalation processes. Our results presented here are helpful in understanding the mechanism of lithium intercalation into nanotube bundles, which may potentially be applied in the development of CNT based electrodes.

Communication: Asymmetrical cation movements through G-quadruplex DNA.

G-quadruplex is a specific DNA structure stabilized by cations dwelling between adjacent G-quartets. The cation which dwelling in the coordination sites can move to the bulk solution through two terminals of G-quadruplex in an asymmetrical manner. In this study, we used molecular dynamics simulations and adaptive biasing force method to investigate the influence of glycosidic bond orientations of guanosines on the moving of cations through the G-quartet. We found that syn glycosidic bond orientation penalizes the escaping of K(+) ions, which results in the asymmetrical cation movements through the two terminals of G-quadruplexes. Nonetheless, the syn orientations have slight influence on the energy barrier for Na(+) ions penetrating the terminal G-quartets because of its relatively smaller radius. This study contributes to the understanding of the asymmetrical cation displacement in G-quadruplex systems.

Nonlinear relationship between triglycerides and cognitive function after acute ischemic stroke among older adults.

Background: Although studies have explored the association between triglyceride levels and cognitive function after acute ischemic stroke (AIS), the results have been conflicting. Therefore, the purpose of this study was to investigate the relationship between triglyceride levels and cognitive function after AIS among older adults. Methods: This is an observational cross-sectional study. From November 2022 to June 2023, we consecutively collected patients diagnosed with AIS in China. Triglyceride levels were measured within 24 h of admission. The Mini-Mental State Examination (MMSE) was used to assess cognitive function. Nonlinear associations between triglyceride levels and cognitive function were assessed using smooth curve fitting and threshold effect analysis. Results: In this study, a total of 221 patients (mean ± SD: 70.64 ± 7.43 years) with AIS were consecutively recruited, among whom 144 (65.16%) were male. Among the 221 recruited patients, 102 (46.15%) had cognitive impairment. Triglyceride levels and cognitive impairment were found to have a nonlinear association after controlling for potential confounders, with an inflection point at 0.8 mmol/L. Below the inflection point, triglyceride levels were positively correlated with MMSE scores (ß = 14.11, 95% confidence interval [CI] = 2.33-25.89, P = 0.020). However, above the inflection point, the correlation between MMSE score and triglyceride levels was not statistically significant (ß = 1.04, 95% CI = -1.27 - 3.34, P = 0.380). Conclusion: There is a nonlinear association between triglyceride levels and cognitive function after AIS in older adults. Triglyceride was positively connected with cognitive function when it was less than 0.8 mmol/L.

Helicity-directed recognition of bacterial phospholipid via radially amphiphilic antimicrobial peptides.

The fundamental differences in phospholipids between bacterial and mammalian cell membranes present remarkable opportunities for antimicrobial design. However, it is challenging to distinguish bacterial anionic phospholipid phosphatidylglycerol (PG) from mammalian anionic phosphatidylserine (PS) with the same net charge. Here, we report a class of radially amphiphilic α helix antimicrobial peptides (RAPs) that can selectively discriminate PG from PS, relying on the helix structure. The representative RAP, L10-MMBen, can direct the rearrangement of PG vesicles into a lamellar structure with its helix axis parallel to the PG membrane surface. The helical structure imparts both the thermodynamic and kinetic advantages of L10-MMBen/PG assembly, and the hiding of hydrophobic regions in RAPs is crucial for PG recognition. L10-MMBen exhibits high selectivity against bacteria depending on PG recognition, showing low in vivo toxicity and significant treatment efficacy in mice infection models. Our study introduces a helicity-direct bacterial phospholipid recognition paradigm for designing highly selective antimicrobial peptides.

The Prevalence of Social Frailty Among Older Adults: A Systematic Review and Meta-Analysis.

OBJECTIVE: To report the overall prevalence of social frailty among older people and provide information for policymakers and authorities to use in developing policies and social care. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: We searched 4 databases (PubMed, Embase, Web of Science, and Google Scholar) to find articles from inception to July 30, 2022. We included cross-sectional and cohort studies that provided the prevalence of social frailty among adults aged 60 years or older, in any setting. METHODS: Three researchers independently reviewed the literature and retrieved the data. A risk of bias tool was used to assess each study's quality. A random-effect meta-analysis was performed to pool the data, followed by subgroup analysis, sensitivity analysis, and meta-regression. RESULTS: From 761 records, we extracted 43 studies with 83,907 participants for meta-analysis. The pooled prevalence of social frailty in hospital settings was 47.3% (95% CI: 32.2%-62.4%); among studies in community settings, the pooled prevalence was 18.8% (95% CI: 14.9%-22.7%; P < .001). The prevalence of social frailty was higher when assessed using the Tilburg Frailty Indicator (32.3%; 95% CI: 23.1%-41.5%) than the Makizako Social Frailty Index (27.7%; 95% CI: 21.6%-33.8%) or Social Frailty Screening Index (13.4%; 95% CI: 8.4%-18.4%). Based on limited community studies in individual countries using various instruments, social frailty was lowest in China (4.9%; 95% CI: 4.2%-5.7%), followed by Spain (11.6%; 95% CI: 9.9%-13.3%), Japan (16.2%; 95% CI: 12.2%-20.3%), Korea (26.6%; 95% CI: 7.1%-46.1%), European urban centers (29.2%; 95% CI: 27.9%-30.5%), and the Netherlands (27.2%; 95% CI: 16.9%-37.5%). No other subgroup analyses showed any statistically significant prevalence difference between groups. CONCLUSION AND IMPLICATIONS: The prevalence of social frailty among older adults is high. Settings, country, and method for assessing social frailty affected the prevalence. More valid comparisons will await consensus on measurement tools and more research on geographically representative populations. Nevertheless, these results suggest that public health professionals and policymakers should seriously consider social frailty in research and program planning involving older adults.