Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.

Direct Access to Thio- and Seleno-acetamides Bearing (Benzo)thiazoles by a Base-Promoted One-Pot Two-Step Three-Component Reaction of 2-Amino(benzo)thiazoles with Aryl Acetyl Chlorides and Dichalcogenides.

Highly efficient and practical carbon-chalcogen (S, Se) and amide bonds formation methodologies for the synthesis of thio- and seleno-acetamides were developed, via the base-promoted one-pot two-step reactions of 2-amino(benzo)thiazoles and aryl acetyl chlorides with dichalcogenides. This cross-coupling reaction afforded the goal products that had been chalcogenated regioselectively in moderate to good yields. Further transformations of the new synthesized compounds, DFT calculations and preliminary mechanism studies are discussed as well.

V-shaped chiral hosts based on π-extended hematoxylin.

Hematoxylin has a V-shaped chiral geometry, but its potential in chiroptical self-assembled materials is underdeveloped. Herein, three novel V-shaped chiral hematoxylin derivatives were synthesized, and they showed extended skeletons as well as photophysical and chiroptical behaviors. Moreover, their host-guest interactions with C60 were investigated. Our findings could aid in the design and synthesis of novel chiral host molecules from natural products.

Survival benefit of adjuvant chemotherapy in elderly patients with stage I triple-negative breast cancer: a cohort study based on the SEER database.

Background: This study analyzed the trend and prognostic role of postoperative adjuvant chemotherapy (POCT) in patients with stage I triple-negative breast cancer (TNBC) aged more than 65 years. In addition, the relationship between POCT and survival rate was also determined. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was collected to determine 3,307 TNBC elderly women aged ≥65 years between 2010 and 2016, and they were divided into POCT and non-POCT groups. Propensity score matching (PSM) method was used to offset the differences in baseline characteristics between the groups. Kaplan-Meier plots were tested to contrast overall survival (OS) and breast cancer-specific survival (BCSS) between the two groups. The Cox proportional hazard model was constructed to assess the prognostic factors affecting OS and BCSS. Results: Younger age, higher histological grade, married, postoperative radiotherapy, lumpectomy, larger tumor, and closer year of diagnosis were related to an enhanced likelihood of adjuvant chemotherapy. After PSM, POCT was related to increased 5-year OS [hazard ratio (HR): 0.571, 95% confidence interval (CI): 0.432-0.753, respectively], without significant difference in BCSS improvement. Exploratory subgroup analysis demonstrated that POCT contributed to OS improvement in both IA and IB patients, but did not improve BCSS in IA and IB patients. Conclusions: In elderly patients ≥65 years, POCT improved 5-year OS in stage I TNBC patients, while further exploration with larger prospective trials are needed.

Efficient chirality transfer from chiral amines to oligo(p-phenylenevinylene)s to fabricate chiroptical materials.

Oligo(p-phenylenevinylene) (OPV)-based luminophores show versatile luminescence properties based on their structural and packing arrangements, and however have seldomly been utilized in fabricating chiroptical materials. Here, we report a co-assembly strategy to introduce hydrophilic chiral amines into OPV-appended carboxylic acids via salt-bridge type hydrogen bonds. The coassembly in aqueous media allows for efficient chirality transfer with chiroptical activities. The participation of chiral amines altered the aromatic stacking from H- to J-type, which greatly enhanced the luminescence of the OPV compounds and facilitated the emergence of Cotton effects as well as circularly polarized luminescence. This work demonstrates the successful coassembly of OPV luminophores into chiral assemblies with tunable optical activity, showing potential for chiroptical application in optical chirality sensing.

Antibody engineering-driven controllable chemiluminescence resonance energy transfer for immunoassay with tunable dynamic range.

The donor-acceptor distance is a critical factor for the occurrence of chemiluminescent resonance energy transfer (CRET). We herein evaluate the donor-acceptor distance and transfer efficiency of CRET immunoassays of a series of donors which contain different sized antibody fragments, intact monoclonal antibody (IgG), antigen binding fragment (Fab), and single chain fragment antibody (scFv). Core/multishell quantum dots were used as the acceptor in three CRET systems. IgG is the maximum antibody fragment, leading to the longest donor-acceptor distance and the lowest transfer efficiency. Donors with Fab and scFv show significantly decreased distance and increased transfer efficiency. These results suggest an inverse correlation between donor size and transfer efficiency and can be used to provide guidance for the construction of controllable CRET. By combining the controllable CRET with immunoassay, we further develop a tunable sulfamethazine analytical system. Three different sized donors based CRET immunoassay show a markedly different sensitivity and dynamic range. Such adjustable detection provides greater flexibility for contaminant detection in different foodstuffs with different residue limits. This work not only illustrates the effect of donor-acceptor distance on regulating the energy transfer efficiency of CRET system, but also provides a guideline for the construction of a tunable immunoassay.

An Aggregation-Induced Emission-Based Indirect Competitive Immunoassay for Fluorescence "Turn-On" Detection of Drug Residues in Foodstuffs.

A new fluorescent "turn-on" probe-based immunosensor for detecting drug residues in foodstuffs was established by combining the mechanism of aggregation-induced emission (AIE) and an indirect competitive enzyme-linked immunosorbent assay (ELISA). In this study, a luminogen, with negligible fluorescence emission (TPE-HPro), aggregated in the presence of H2O2, and exhibited astrong yellow emission based on its AIE characteristics. This AIE process was further configured into an immunoassay for analyzing drug residues in foodstuffs. In this approach, glucose oxidase (GOx) was used as an enzyme label for the immunoassay and triggered GOx/glucose-mediated H2O2 generation, which caused oxidation of TPE-HPro and a "turn-on" fluorescence response at 540 nm. To quantitatively analyze the drug residues in foodstuffs, we used amantadine (AMD) as an assay model. By combining the AIE-active "turn-on" fluorescent signal generation mechanism with conventional ELISAs, quantifying AMD concentrations in chicken muscle samples was realized with an IC50 (50% inhibitory concentration) value of 0.38 ng/mL in buffer and a limited detection of 0.06 µg/kg in chicken samples. Overall, the conceptual integration of AIE with ELISA represents a potent and sensitive strategy that broadens the applicability of the AIE-based fluorometric assays.

Class-Specific Monoclonal Antibodies and Dihydropteroate Synthase in Bioassays Used for the Detection of Sulfonamides: Structural Insights into Recognition Diversity.

Molecular recognition between a receptor and ligand is a fundamental event in bioanalytical assays, which guarantees the sensitivity and specificity of an assay for the detection of the target of interest. An intensive understanding of the interaction mechanism could be useful for desirable hapten design, directed antibody evolution in vitro, and assay improvement. To illustrate the structural information on class-specific monoclonal antibodies (mAbs) and dihydropteroate synthase (DHPS) against sulfonamides (SAs) we have previously prepared, we initially measured the kinetic parameters of mAb 4C7, 4D11, and DHPS, which showed that the affinities of 4C7 and 4D11 were in the pM to µM range, while DHPS was uniformly in the µM range. Three-dimensional quantitative structure-activity relationship analysis for 4C7 and 4D11 then revealed that the contributions from the stereochemical structure and electron density of the SAs were comparable to binding with mAb. To acquire insights into the structural basis of mAbs and DHPS during the recognition process, the crystal structures of 4C7 and its complex with sulfathiazole were determined using X-ray crystallography. The results showed the SAs orientation and hydrogen bonding interactions mainly contributed to the diverse SAs-mAb affinities. However, for DHPS, a nucleophilic substitution reaction occurred during the recognition process with the SAs, which contributed to the surprisingly uniform affinity for all the SAs tested. This study verified the previous hypotheses on antibody production against SAs and enhanced our understanding of antibody-SAs interactions, which provided useful information toward the rational design of novel haptens and directed evolution to produce class-specific antibodies as DHPS.

pH-Responsive Dipeptide-Based Dynamic Covalent Chemistry Systems Whose Products and Self-Assemblies Depend on the Structure of Isomeric Aromatic Dialdehydes.

Facile control over preparation of organic building blocks and self-assembled aggregations to construct the desired materials remains challenges. This article reports selective dynamic covalent bonds formation and the corresponding self-assembly behaviors by using a dipeptide, glycylglycine (GlyGly), reacting with isomeric aromatic dialdehydes o-phthalaldehyde (OPA), p-phthalaldehyde (PPA), and m-phthalaldehyde (MPA) to demonstrate diversified aggregation forms caused by structure topology variations. Under alkaline condition, the aldehyde groups of phthalaldehydes can be connected with the amino groups of GlyGly by imine bonds as the dynamic chemical bonds. Owing to the fact that formation and dissociation of the imine bonds were reversibly pH-responsive, the reactions and aggregates assembled by their products were also reversibly controlled by changing pH. Three products, including two-armed product (OPGG, in which two GlyGly molecules were connected with one OPA molecule), single-armed product (PPG, in which only one GlyGly molecule was connected with a PPA molecule), and a mixture product (MPGG and MPG), as well as their different self-assembly behaviors, were obtained from OPA/GlyGly, PPA/GlyGly, and MPA/GlyGly systems, respectively, at the same condition of pH 8.6 in 90% methanol aqueous solution. However, for OPA/GlyGly system, another different type of product with benzopyrrole structure (OPG) was obtained by nucleophilic substitution via mixing OPA and GlyGly in water, which generated organic nanoparticles. Based on the results above, we conjectured the differences in dynamic covalent bond formation and supramolecular assembly clearly were influenced by the structure topologies of phthalaldehydes (OPA, PPA, and MPA). The experimental phenomenon verified the hypothesis as well, which may guide us to realize facile construction of selective reaction products and intelligent reversibly responsive materials with diverse morphologies and functions.

Highly sensitive visual detection of amantadine residues in poultry at the ppb level: A colorimetric immunoassay based on a Fenton reaction and gold nanoparticles aggregation.

Colorimetric biosensors for the on-site visual detection of veterinary drug residues are required for food control in developing countries and other resource-constrained areas, where sophisticated instruments may not be available. In this study, we developed a highly sensitive immunoassay for amantadine residues in poultry. By introducing a novel signal generation strategy into an indirect competitive immunoassay, a highly sensitive assay for amantadine residues in chicken was achieved for naked eye readout at the part per billion (ppb) level. Signal amplification was achieved in the designed immunoassay by combining conventional indirect competitive enzyme-linked immunosorbent assay, Fenton reaction-regulated oxidation of cysteine, and gold nanoparticle aggregation. Therefore, the cascade reaction remarkably enhanced the assay sensitivity and led to a pronounced color change from red to dark purple in the solution, which could be easily distinguished with the naked eye even at approximately 1 µg kg-1 in poultry muscle. Moreover, the color change can be quantitatively assayed with a classic high-throughput plate reader for contaminated poultry samples. The limit of detection (LOD) was 0.51 nM (0.095 ng mL-1). The recovery rates for spiked chicken samples ranged from 78% to 84% with relative standard deviations <15%. Therefore, we propose that this immunoassay could be generally applicable for on-site detection in the field of food control.

Highly sensitive SERS immunosensor for the detection of amantadine in chicken based on flower-like gold nanoparticles and magnetic bead separation.

Here we report a novel ultrasensitive surface-enhanced Raman scattering (SERS) immunosensor based on the flower-like gold nanoparticles (AuNFs) and magnetic bead separation for homogeneous detection of amantadine (AMD) in chicken just by one-step. The 5, 5'-dithiobis (2-nitrobenzoicacid) (DTNB) modified AuNFs and N-(1-adamantyl) ethylenediamine (AEDA) conjugated denatured BSA (AEDA-dBSA) was used as the SERS nanoprobe. And the capture probe was anti-AMD monoclonal antibody (mAbs)-functionalized magnetic beads (MNBs-mAbs). An immunoreaction occurred between free AMD and SERS nanoprobe for competing limited binding sites of MNBs-mAbs. This work combined inherent sensitive property of SERS with antibody-antigen highly specificity recognition for the AMD detection. The analytical results showed that the SERS-based immunosensor was sensitive, simple and reliable with a limit of detection (LOD) of 0.005 ng/mL for AMD, which were 2 orders of magnitude better than an enzyme-linked immunosorbent assay based on the same immunoreagents. Analysis of AMD-spiked chicken samples revealed that the developed immunosensor provided accepted recoveries ranging from 74.76%-89.34% with coefficient of variation less than 15.04%. This strategy represents a simple, reliable, and universal approach for detection of chemical contaminants in food samples.

Synthesis and Binding Properties of Monohydroxycucurbit[7]uril: A Key Derivative for the Functionalization of Cucurbituril Hosts.

We present a simple, direct method to prepare monohydroxylated cucurbit[7]uril (CB7-OH) through the direct oxidation of its precursor host, cucurbit[7]uril (CB7). Although the conversion takes place in low yield (14%), the isolation of CB7-OH from the reaction mixture is straightforward, and the unreacted CB7 can be easily recovered. ITC measurements with several selected guests confirmed that CB7-OH binds all of them in aqueous solution with similar, albeit slightly lower, binding affinities than those observed with the unmodified CB7 host. ESI mass spectrometric competition experiments are consistent with the ITC measurements. A variety of spectroscopic and voltammetric measurements also verify that the CB7-OH complexes exhibit properties essentially identical to those of the CB7 complexes. DFT computational data also confirm the similar thermodynamic stabilities and structures of the CB7-OH and CB7 inclusion complexes. Finally, the high thermodynamic stability of the CB7-OH complexes was used to improve on the extraction efficiency of stir bar sorptive extraction methods after suitable modification of the active coating with CB7-OH.

Molecularly Imprinted Polymer as an Antibody Substitution in Pseudo-immunoassays for Chemical Contaminants in Food and Environmental Samples.

The chemical contaminants in food and the environment are quite harmful to food safety and human health. Rapid, accurate, and cheap detection can effectively control the potential risks derived from these chemical contaminants. Among all detection methods, the immunoassay based on the specific interaction of antibody-analyte is one of the most widely used techniques in the field. However, biological antibodies employed in the immunoassay usually cannot tolerate extreme conditions, resulting in an unstable state in both physical and chemical profiles. Molecularly imprinted polymers (MIPs) are a class of polymers with specific molecular recognition abilities, which are highly robust, showing excellent operational stability under a wide variety of conditions. Recently, MIPs have been used in biomimetic immunoassays for chemical contaminants as an antibody substitute in food and the environment. Here, we reviewed these applications of MIPs incorporated in different analytical platforms, such as enzyme-linked immunosorbent assay, fluorescent immunoassay, chemiluminescent immunoassay, electrochemical immunoassay, microfluidic paper-based immunoassay, and homogeneous immunoassay, and discussed current challenges and future trends in the use of MIPs in biomimetic immunoassays.

A controllable etching supramolecular hydrogel based on metal ions.

We report an interesting gel-etching system in which a gel can be etched with corresponding etching rates and color changes when different types of etching molecules are added to the gel. This gel system may have wide potential application in molecular recognition, pre-packaged, as well as other functional materials.

Self-assemblies of cyclodextrin derivatives modified by ferrocene with multiple stimulus responsiveness.

Two novel cyclodextrin derivatives were synthesized that could self-assemble into a supramolecular polymer and gel in different solvent environments. Importantly, the obtained self-assemblies, including vesicles, micro-fibers and gels, could respond to various external stimuli efficiently.

Facile Stimuli-Responsive Transformation of Vesicle to Nanofiber to Supramolecular Gel via ω-Amino Acid-Based Dynamic Covalent Chemistry.

This paper reports an interesting type of self-assembly systems based on dynamic covalent bonds. The systems are pH-responsible and reversible, which could be utilized for controlling the morphology transformation of the assemblies. In alkaline conditions, the amine group of 11-aminoundecanoic acid (AUA) can connect with the aldehyde group of benzaldehyde (BA) or 1-naphthaledhyde (NA) by dynamic covalent bond to form a small organic building block accompanied by the morphological transformation from vesicles to fibers. When pH is lowered to a neutral value, the dynamic covalent bonds (imine bonds) can be hydrolyzed, leading to the dissociation of fibers and appearance of spherical aggregates. The transformation was confirmed reversible as fibers appeared again when the pH was changed back to alkaline value. In addition, a reversibly controlled gel was designed based on the nanofiber formation. NaCl, which is capable of greatly enhance the nanofiber density and cross-linking, was used to induce the growth of free-standing gel from free-flowing nanofiber system, and the resultant gel was proven to be pH-reversible.

Chemiluminescence Resonance Energy Transfer Competitive Immunoassay Employing Hapten-Functionalized Quantum Dots for the Detection of Sulfamethazine.

We describe a new strategy for using chemiluminescence resonance energy transfer (CRET) by employing hapten-functionalized quantum dots (QDs) in a competitive immunoassay for detection of sulfamethazine (SMZ). Core/multishell QDs were synthesized and modified with phospholipid-PEG. The modified QDs were functionalized with the hapten 4-(4-aminophenyl-sulfonamido)butanoic acid. The CRET-based immunoassay exhibited a limit of detection for SMZ of 9 pg mL(-1), which is >4 orders of magnitude better than a homogeneous fluorescence polarization immunoassay and is 2 orders of magnitude better than a heterogeneous enzyme-linked immunosorbent assay. This strategy represents a simple, reliable, and universal approach for detection of chemical contaminants.

Controlled self-organization of cyanostilbene: emission tuning and photo-responsiveness.

Cyanostilbene modified with dimethylaniline (CMD) could self-assemble into vesicles and fibrous morphologies depending on the solvophobic properties. Furthermore, morphology of well-defined nanostructures could be changed with enhanced emission triggered by the photo-isomerization of cyanostilbene. The present system has potential for building luminescent color conversion materials.

Light and cucurbit[7]uril complexation dual-responsiveness of a cyanostilbene-based self-assembled system.

A cyanostilbene-based amphiphile (CS) was synthesized, which could self-assemble into non-emissive bilayer vesicles and ultra-thin ribbons. Cucurbit[7]uril (CB[7]) could form an inclusion complex with CS with a significant hypochrome effect, giving a strong blue emission from non-emissive species. CS underwent photoisomerization induced by light irradiation, which allowed the membrane contraction into smaller vesicles.

An easy approach for constructing vesicles by using aromatic molecules with ß-cyclodextrin.

Vesicles were formed in aqueous solution using ß-cyclodextrin (ß-CD) complexes with a series of ultra-small aromatic molecules. The vesicles are easy to prepare without a complicated synthesis procedure and their structure was identified and characterized using various techniques, including transmission electron microscopy, atomic force microscopy and dynamic laser light scattering. Using the ß-CD/l-phenylalanine system as a representative example, the structural factors that caused the self-assembly were revealed using proton nuclear magnetic resonance, Fourier transform infrared spectroscopy and X-ray diffraction. In addition, the vesicular architecture could be endowed with a diverse range of stimuli-responses, as a consequence of the selective addition of various guest molecules. It is anticipated that this novel assembly strategy could be further extended, and that it presents new opportunities for the development of nanocarriers and soft materials.