Photoactivated Hydrogen Sulfide Donor with a Near-Infrared Fluorescence Report System for Accelerated Chronic Wound Healing.

Delayed wound healing is one of the major diabetes complications that occur in 25% of diabetic patients. Specific wound management and combination treatment are required to repair the wound, which still remains a challenge with few effective therapies available currently. In this work, a new H2S donor PRO-F, which is characterized by the capability to promote wound healing in diabetes, was designed. PRO-F can be activated by light without consuming endogenous substances and the accompanying fluorescent signal makes the real-time tracking of released H2S possible. PRO-F is able to deliver H2S in an intracellular environment with moderate release efficiency (50%), which presents cytoprotective effects against excessive reactive oxygen species (ROS) induced damage. Furthermore, the potential of PRO-F to enhance chronic wound healing was validated by employing diabetic models. This work provides new insights into the therapeutic role of H2S donors in complex wound conditions, which should advance the pathophysiological research associated with H2S.

Molecular and thermodynamic insights into interfacial interactions between collagen and cellulose investigated by molecular dynamics simulation and umbrella sampling.

Cellulose/collagen composites have been widely used in biomedicine and tissue engineering. Interfacial interactions are crucial in determining the final properties of cellulose/collagen composite. Molecular dynamics simulations were carried out to gain insights into the interactions between cellulose and collagen. It has been found that the structure of collagen remained intact during adsorption. The results derived from umbrella sampling showed that (110) and ([Formula: see text]) faces exhibited the strongest affinity with collagen (100) face came the second and (010) the last, which could be attributed to the surface roughness and hydrogen-bonding linkers involved water molecules. Cellulose planes with flat surfaces and the capability to form hydrogen-bonding linkers produce stronger affinity with collagen. The occupancy of hydrogen bonds formed between cellulose and collagen was low and not significantly contributive to the binding affinity. These findings provided insights into the interactions between cellulose and collagen at the molecular level, which may guide the design and fabrication of cellulose/collagen composites.

Activatable Near-Infrared Fluorescent Organic Nanoprobe for Hypochlorous Acid Detection in the Early Diagnosis of Rheumatoid Arthritis.

Early diagnosis of rheumatoid arthritis (RA) is crucial to prevent deterioration and improve the prognosis of disease outcome. However, current clinical diagnostic methods are unable to achieve accurate and early detection of RA. In this work, we designed an activatable organic nanoprobe (ONP-CySe) capable of specific and real-time imaging of ClO- in early RA. ONP-CySe comprises a near-infrared fluorescent selenomorpholine-caged cyanine dye as the sensing component and an amphiphilic triblock copolymer triphenyl phosphine derivative for mitochondria targeting. Our results showed that ONP-CySe successfully detected elevated levels of ClO- in the mitochondria of macrophages with high selectivity, low limit of detection (31.5 nM), excellent photostability, and good biocompatibility. Furthermore, ONP-CySe can also be used to monitor anti-inflammatory responses and efficacies of RA therapeutics, such as selenocysteine and methotrexate, in BALB/c mouse models. Therefore, our research proposes a universal molecular design strategy for the detection of ClO-, which holds potential for early diagnosis and drug screening for RA.

An Activatable Near-Infrared Fluorescence Hydrogen Sulfide (H2S) Donor for Imaging H2S Release and Inhibiting Inflammation in Cells.

Hydrogen sulfide (H2S) is a vital endogenous signal molecule that exerts critical physiological functions such as biological regulation and cytoprotection. Despite significant progress in developing H2S donors, site-specific delivery and controllable release of H2S in biological systems remain a key challenge. Herein, we develop new Cys-triggered fluorescent H2S donor Pro-S that is composed of a dicyanoisophorone-based near-infrared (NIR) fluorescent dye and a thiocarbamate moiety. The H2S donor releases H2S under the attack of Cys, accompanied by the release of a fluorescent reporter, which enables the real-time capturing of H2S by fluorescence spectroscopy or microscopy. Pro-S exhibits strong NIR fluorescence enhancement (70-fold), excellent controllable H2S release (30 min), high H2S release efficiency (62%), and well live-cell compatibility, allowing for visualization of H2S release in cells and zebrafish. Moreover, Pro-S presents a good effect of anti-inflammation in RAW 264.7 cells. This work provides a new idea for the design of H2S donors, which may be beneficial to the comprehension of the potential mechanism of inflammation and optimization of treatment strategies.

Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of cyclin-dependent-like kinase 5.

Melatonin helps to maintain circadian rhythm, exerts anticancer activity, and plays key roles in regulation of glucose homeostasis and energy metabolism. Glycosylation, a form of metabolic flux from glucose or other monosaccharides, is a common post-translational modification. Dysregulated glycosylation, particularly O-GlcNAcylation, is often a biomarker of cancer cells. In this study, elevated O-GlcNAc level in bladder cancer was inhibited by melatonin treatment. Melatonin treatment inhibited proliferation and migration and enhanced apoptosis of bladder cancer cells. Proteomic analysis revealed reduction in cyclin-dependent-like kinase 5 (CDK5) expression by melatonin. O-GlcNAc modification determined the conformation of critical T-loop domain on CDK5 and further influenced the CDK5 stability. The mechanism whereby melatonin suppressed O-GlcNAc level was based on decreased glucose uptake and metabolic flux from glucose to UDP-GlcNAc, and consequent reduction in CDK5 expression. Melatonin treatment, inhibition of O-GlcNAcylation by OSMI-1, or mutation of key O-GlcNAc site strongly suppressed in vivo tumor growth. Our findings indicate that melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of CDK5.

Confirmation of Suzuki-Miyaura Cross-Coupling Reaction Mechanism through Synthetic Architecture of Nanocatalysts.

Despite widespread use of heterogeneous Pd catalysts in Suzuki-Miyaura coupling reactions, detailed roles of Pd, especially the nature of its active species, are still a topic of controversial debate. While some studies showed an active surface of Pd nanoparticles or nanoclusters acting heterogeneously, others claimed soluble Pd species leached from the metallic Pd to be active species which are homogeneous in nature. Besides, within the homogeneous mechanism, how the Pd leaches and promotes the cross-coupling reaction is then another question that needs to be addressed. It could be envisioned that if the soluble Pd species and solid-phase Pd are physically separated, the mechanism of Suzuki-Miyaura coupling could then be confirmed through examining the catalytic activity in different reaction regions. Herein we use microporous Stöber silica as a membrane to separate the soluble Pd species from solid Pd and conduct size-selective reactions which allow the passage of leaching Pd species, but not of reactants or products larger than the membrane aperture. With this strategy, we have been able to differentiate the surface reaction from the solution cross-coupling. We find that the leached Pd species are the only genuine catalytic intermediate in the cross-coupling reactions. We also confirm that oxidative addition of aryl halides to the solid Pd leads to leaching of the soluble Pd species which is necessary to promote Suzuki-Miyaura reactions.

Activatable Formation of Emissive Excimers for Highly Selective Detection of ß-Galactosidase.

Small-molecular fluorescence sensors have become promising detection tools in many fields attributing to their high sensitivity, excellent temporal and spatial resolution, and low cytotoxicity. However, high concentration or aggregation-induced fluorescence quenching effect has usually hindered the development of traditional fluorescence dyes. Herein, a new fluorophore cyanovinylene dye BMZ with excimer emission property has been constructed. It shows an obvious enhanced and red-shift emission upon aggregation in aqueous solution, which overmatches the conventional pyrene with longer absorption and emission wavelengths. Using this unique optical property, a new fluorescence probe BMZ-Gal has been developed for trapping of ß-galactosidase (ß-Gal) activity with high selectivity, low limit of detection of 0.17 U, and rapid recognition, which is based on the ß-Gal-induced formation of red-shift emitting excimer. ß-Gal has a strong affinity for BMZ-Gal, which is verified through the Michaelis-Menten constants (Km, 1.87 µM) and the hydrolysis efficiencies (Kcat/Km, 1.78 × 103 M-1 s-1). Furthermore, the assay system has been successfully used for detecting endogenous ß-Gal in living ovarian cancer cells and can passively targeted to identify ß-Gal in organelle level and determine its subcellular location with satisfactory accuracy. We anticipate that the new fluorophore cyanovinylene dye herein may inaugurate new opportunities for the development of excimer emission sensors.

Hyperfast Water Transport through Biomimetic Nanochannels from Peptide-Attached (pR)-pillar[5]arene.

Synthetic water channels offer great promise to replace natural aquaporins (AQPs) for making new-generation biomimetic membranes for water treatment. However, the water permeability of the current synthetic water channels is still far below that of AQPs. Here, peptide-attached (pR)-pillar[5]arene (pR-PH) channels are reported to mimic the high permeability of AQPs. It is demonstrated that the pR-PH channels with an open pore can transport water smoothly and efficiently. The pR-PH channels are competitive with AQPs in terms of water permeability and are much superior to diastereomer peptide-attached (pS)-pillar[5]arene (pS-PH) and other reported synthetic water channels. The exceptional water-transport properties of the pR-PH channels are further demonstrated in a composite polymeric membrane that incorporates the nanochannels into the top selective layer. This membrane gives a significantly improved water flux while retaining high salt rejection. The results establish a tangible foundation for developing highly efficient artificial water channel-based biomimetic membrane for water purification applications.

Stabilities and structures of islet amyloid polypeptide (IAPP22-28) oligomers: from dimer to 16-mer.

BACKGROUND: The formation of amyloid fibrils is associated with many age-related degenerative diseases. Nevertheless, the molecular mechanism that directs the nucleation of these fibrils is not fully understood. METHODS: Here, we performed MD simulations for the NFGAILS motif of hIAPP associated with the type II diabetes to estimate the stabilities of hIAPP22-28 protofibrils with different sizes: from 2 to 16 chains. In addition, to study the initial self-assembly stage, 4 and 8 IAPP22-28 chains in explicit solvent were also simulated. RESULTS: Our results indicate that the ordered protofibrils with no more than 16 hIAPP22-28 chains will be structurally stable in two layers, while one-layer or three-layer models are not stable as expected. Furthermore, the oligomerization simulations show that the initial coil structures of peptides can quickly aggregate and convert to partially ordered ß-sheet-rich oligomers. CONCLUSIONS: Based on the obtained results, we found that the stability of an IAPP22-28 oligomer was not only related with its size but also with its morphology. The driving forces to form and stabilize an oligomer are the hydrophobic effects and backbone H-bond interaction. Our simulations also indicate that IAPP22-28 peptides tend to form an antiparallel strand orientation within the sheet. GENERAL SIGNIFICANCE: Our finding can not only enhance the understanding about potential mechanisms of hIAPP nuclei formation and the extensive structural polymorphisms of oligomers, but also provide valuable information to develop potential ß-sheet formation inhibitors against type II diabetes.

Naked-eye and near-infrared fluorescence probe for hydrazine and its applications in in vitro and in vivo bioimaging.

Hydrazine has been applied diffusely in most of the chemical industry; however, it is a hazardous environmental pollutant and highly toxic to organisms. Selective, rapid, and sensitive detection of hydrazine thus becomes absolutely necessary in both biological and environmental sciences. Accordingly, fluorescence probes for hydrazine have been paid great attention in recent years. Disclosed here is the near-infrared (NIR) fluorescence probe with a turn-on fluorescent probe CyJ based on the structure-emission property relationships of the NIR dyes containing an acetyl group as the recognizing moiety. This new probe not only can be readily prepared, but also shows excellent sensing properties. First and most important of all, CyJ is highly selective for N2H4 over various anions, cations, and other amino compounds and has a low limit of detection (LOD) of hydrazine (5.4 ppb as fluorescence sensor and 6.1 ppb as UV sensor). Besides, CyJ exhibited a dramatic increase in fluorescence at λmax = 706 nm in the presence of N2H4, and it offers a rapid, colorimetric and vapor sensing detection process for N2H4 in both aqueous solution and diluted human serum. Furthermore, CyJ has good cell-membrane permeability and low cytotoxicity. In addition, we have successfully applied the CyJ to visualize N2H4 in live mouse and, for the first time, in tissues such as the liver, lung, kidney, heart, and spleen.

Near-infrared and naked-eye fluorescence probe for direct and highly selective detection of cysteine and its application in living cells.

The near-infrared (NIR) fluorescence sensor for rapid, selective, and sensitive detection of cystenine (Cys) is of great importance in both biological and environmental sciences. Herein, we report a specific probe with turn-on fluorescence property, visible color change with naked-eye, and large wavelength shift on UV spectra for highly selective detection of Cys over homocysteine (Hcy) and glutathione (GSH) in both HEPES buffer (10 mM, pH 7.4) and diluted human serum. The probe based on the conjugate addition-cyclization reaction has a low limit of detection to Cys (0.16 µM as NIR fluorescence sensor and 0.13 µM as UV sensor). Kinetic study indicated that the probe has a very rapid response to Cys, owing to the much higher pseudo-first-order reaction constant with Cys (299 M(-1) s(-1)) than with Hcy (1.29 M(-1) s(-1)) or GSH (0.53 M(-1) s(-1)). Upon addition of Cys to a solution of the probe, the color changed from purple to cyan, with the maximum wavelength shifting from 582 to 674 nm in the UV spectrum and a fluorescence emission at 697 nm appearing. It has been successfully applied for determination of Cys in diluted serum and bioimaging of Cys in living cells with low cell toxicity.

In Silico Identification of Protein S-Palmitoylation Sites and Their Involvement in Human Inherited Disease.

S-Palmitoylation is a key regulatory mechanism controlling protein targeting, localization, stability, and activity. Since increasing evidence shows that its disruption is implicated in many human diseases, the identification of palmitoylation sites is attracting more attention. However, the computational methods that are published so far for this purpose have suffered from a poor balance of sensitivity and specificity; hence, it is difficult to get a good generalized prediction ability on an external validation set, which holds back the further analysis of associations between disruption of palmitoylation and human inherited diseases. In this work, we present a reliable identification method for protein S-palmitoylation sites, called SeqPalm, based on a series of newly composed features from protein sequences and the synthetic minority oversampling technique. With only 16 extracted key features, this approach achieves the most favorable prediction performance up to now with sensitivity, specificity, and Matthew's correlation coefficient values of 95.4%, 96.3%, and 0.917, respectively. Then, all known disease-associated variations are studied by SeqPalm. It is found that 243 potential loss or gain of palmitoylation sites are highly associated with human inherited disease. The analysis presents several potential therapeutic targets for inherited diseases associated with loss or gain of palmitoylation function. There are even biological evidence that are coordinate with our prediction results. Therefore, this work presents a novel approach to discover the molecular basis of pathogenesis associated with abnormal palmitoylation. SeqPalm is now available online at http://lishuyan.lzu.edu.cn/seqpalm , which can not only annotate the palmitoylation sites of proteins but also distinguish loss or gain of palmitoylation sites by protein variations.

Interfacial interactions between spider silk protein and cellulose studied by molecular dynamics simulation.

CONTEXT: Due to their excellent biocompatibility and degradability, cellulose/spider silk protein composites hold a significant value in biomedical applications such as tissue engineering, drug delivery, and medical dressings. The interfacial interactions between cellulose and spider silk protein affect the properties of the composite. Therefore, it is important to understand the interfacial interactions between spider silk protein and cellulose to guide the design and optimization of composites. The study of the adsorption of protein on specific surfaces of cellulose crystal can be very complex using experimental methods. Molecular dynamics simulations allow the exploration of various physical and chemical changes at the atomic level of the material and enable an atomic description of the interactions between cellulose crystal planes and spider silk protein. In this study, molecular dynamics simulations were employed to investigate the interfacial interactions between spider silk protein (NTD) and cellulose surfaces. Findings of RMSD, RMSF, and secondary structure showed that the structure of NTD proteins remained unchanged during the adsorption process. Cellulose contact numbers and hydrogen bonding trends on different crystalline surfaces suggest that van der Waals forces and hydrogen bonding interactions drive the binding of proteins to cellulose. These findings reveal the interaction between cellulose and protein at the molecular level and provide theoretical guidance for the design and synthesis of cellulose/spider silk protein composites. METHODS: MD simulations were all performed using the GROMACS-5.1 software package and run with CHARMM36 carbohydrate force field. Molecular dynamics simulations were performed for 500 ns for the simulated system.

Molecular insights into inhibiting effects of lignin on cellulase investigated by molecular dynamics simulation.

The hydrolysis of lignocellulose into fermentable monosaccharides using cellulases represents a critical stage in lignocellulosic bioconversion. However, the inactivation of cellulase in the presence of lignin is attributed to the high cost of biofinery. To address this challenge, a comprehensive investigation into the structure-function relationship underlying lignin-driven cellulase inactivation is essential. In this study, molecular docking and molecular dynamics (MD) simulations were employed to explore the impacts of lignin fragments on the catalytic efficiency of cellulase at the atomic level. The findings revealed that soluble lignin fragments and cellulose could spontaneously form stable complexes with cellulase, indicating a competitive binding scenario. The enzyme's structure remained unchanged upon binding to lignin. Furthermore, specific amino acid residues have been identified as involved in interactions with lignin and cellulose. Hydrophobic interactions were found to dominate the binding of lignin to cellulase. Based on the mechanisms underlying the interactions between lignin fragments and cellulase, decreased hydrophobicity and change in the charge of lignin may mitigate the inhibition of cellulase. Furthermore, site mutations and chemical modification are also feasible to improve the efficiency of cellulase. This study may contribute valuable insights into the design of more lignin-resistant enzymes and the optimization of lignocellulosic pretreatment technologies.Communicated by Ramaswamy H. Sarma.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

Influence of the pathogenic mutations T188K/R/A on the structural stability and misfolding of human prion protein: insight from molecular dynamics simulations.

BACKGROUND: Prion diseases are associated with a conformational switch for PrP from PrP(C) to PrP(Sc). Many genetic mutations are linked with prion diseases, such as mutations T188K/R/A with fCJD. SCOPE OF REVIEW: MD simulations for the WT PrP and its mutants were performed to explore the underlying dynamic effects of T188 mutations on human PrP. Although the globular domains are fairly conserved, the three mutations have diverse effects on the dynamics properties of PrP, including the shift of H1, the elongation of native ß-sheet and the conversion of S2-H2 loop to a 3(10) helix. MAJOR CONCLUSIONS: Our present study indicates that the three mutants for PrP may undergo different pathogenic mechanisms and the realistic atomistic simulations can provide insights into the effects of disease-associated mutations on PrP dynamics and stability, which can enhance our understanding of how mutations induce the conversion from PrP(C) to PrP(Sc). General significance Our present study helps to understand the effects of T188K/R/A mutations on human PrP: despite the three pathogenic mutations almost do not alter the native structure of PrP, but perturb its stability. This instability may further modulate the oligomerization pathways and determine the features of the PrP(Sc) assemblies.

Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis.

The rapid emergence of cross-resistance to the integrase strand transfer inhibitors (INSTIs) has become a serious problem in the therapy of human immunodeficiency virus type 1 (HIV-1) infection. Understanding the detailed molecular mechanism of INSTIs cross-resistance is therefore critical for the development of new effective therapy against cross-resistance. On the basis of the homology modeling constructed structure of tetrameric HIV-1 intasome, the detailed molecular mechanism of the cross-resistance mutation E138K/Q148K to three important INSTIs (Raltegravir (RAL, FDA approved in 2007), Elvitegravir (EVG, FDA approved in 2012), and Dolutegravir (DTG, phase III clinical trials)) was investigated by using molecular dynamics (MD) simulation and residue interaction network (RIN) analysis. The results from conformation analysis and binding free energy calculation can provide some useful information about the detailed binding mode and cross-resistance mechanism for the three INSTIs to HIV-1 intasome. Binding free energy decomposition analysis revealed that Pro145 residue in the 140s 1oop (Gly140 to Gly149) of the HIV-1 intasome had strong hydrophobic interactions with INSTIs and played an important role in the binding of INSTIs to HIV-1 intasome active site. A systematic comparison and analysis of the RIN proves that the communications between the residues in the resistance mutant is increased when compared with that of the wild-type HIV-1 intasome. Further analysis indicates that residue Pro145 may play an important role and is relevant to the structure rearrangement in HIV-1 intasome active site. In addition, the chelating ability of the oxygen atoms in INSTIs (e.g., RAL and EVG) to Mg(2+) in the active site of the mutated intasome was reduced due to this conformational change and is also responsible for the cross-resistance mechanism. Notably, the cross-resistance mechanism we proposed could give some important information for the future rational design of novel INSTIs overcoming cross-resistance. Furthermore, the combination use of molecular dynamics simulation and residue interaction network analysis can be generally applicable to investigate drug resistance mechanism for other biomolecular systems.

Converting commonly-used paper into nano-engineered fluorescent biomass-based platform for rapid ClO- quantitative detection in living cells and water sources.

Hypochlorous acid (HClO) and derivative ionic form (ClO-) are significant components of reactive oxygen species, and thus various diseases are correlatively related to the concentration of ClO-. Recently, paper-based indicators have been confirmed to be efficient strategy for sensing hazardous and noxious substances. However, most of these materials can only achieve qualitative detection of the substrates. Herein, an extremely simple manufacturing strategy was proposed to convert commonly-used paper into nano-engineered fluorescent biomass-based platform (CMJL-FP) integrated with on-demand self-assembled colorimetric and ratiometric fluorescence sensor (CMJL) for rapid ClO- quantitative detection in organisms or water sources using smartphones. The CMJL exhibited a highly selective and sensitive ratiometric response to ClO- at a low detection limit (LOD = 92.6 nM). The associating interactions between the fluorescence nano-particles and micro-nano fibers of CMJL-FP ensure good-stability during ClO- detection. It has been experimentally demonstrated that CMJL-FP allows one to realize the rapid quantitative detection of ClO- ions in living cells and large-scale water sources by using color recognition software as part of a simple smartphone. Therefore, integrating the proposed fluorescent paper with smartphones provides an effective, sustainable, cheap and conceptual strategy for quantitative detection of hazardous and noxious substances in organisms and environments.

Exploring structural and thermodynamic stabilities of human prion protein pathogenic mutants D202N, E211Q and Q217R.

The central event in the pathogenesis of prion protein (PrP) is a profound conformational change from its α-helical (PrP(C)) to its ß-sheet-rich isoform (PrP(Sc)). Many single amino acid mutations of PrP are associated with familial prion diseases, such as D202N, E211Q, and Q217R mutations located at the third native α-helix of human PrP. In order to explore the underlying structural and dynamic effects of these mutations, we performed all-atom molecular dynamics (MD) simulations for the wild-type (WT) PrP and its mutants. The obtained results indicate that these amino acid substitutions have subtle effects on the protein structures, but show large changes of the overall electrostatic potential distributions. We can infer that the changes of PrP electrostatic surface due to the studied mutations may influence the intermolecular interactions during the aggregation process. In addition, the mutations also affect the thermodynamic stabilities of PrP.

Cellulose Hollow Annular Nanoparticles Prepared from High-Intensity Ultrasonic Treatment.

Cellulose nanomaterials, such as cellulose nanocrystals (CNCs), have received enormous attention in various material research fields due to their unique properties and green/sustainable nature, among other qualities. Herein, we report hollow-type annular cellulose nanocrystals (HTA-CNCs), which are generated by following a high-intensity ultrasonic treatment. The advanced aberration-corrected transmission electron microscopy results reveal that HTA-CNCs exhibit ring structures with a typical diameter of 10.0-30.0 nm, a width of 3.0-4.0 nm, and a thickness of 2.0-5.0 nm, similar to those of elementary crystallites. The X-ray diffraction measurements show that the as-prepared HTA-CNCs maintain the cellulose I structure. The changes in structure and hydrogen-bonding characteristics of HTA-CNCs are further determined based on the FT-IR results after deconvolution fitting, showing that three types of hydrogen bonds decrease and the content of free OH increases in HTA-CNCs compared with those in the original CNCs. Furthermore, molecular dynamics simulation is carried out to support the experimental study. The formation of HTA-CNCs might be attributed to the structural change and entropy increase. The hollow-type annular CNCs may have broad value-added applications as cellulose nanomaterials in different fields.